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Sample records for included whole-brain diffusion

  1. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

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    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  2. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    International Nuclear Information System (INIS)

    Liu, Yaou; Duan, Yunyun; He, Yong; Yu, Chunshui; Wang, Jun; Huang, Jing; Ye, Jing; Parizel, Paul M.; Li, Kuncheng; Shu, Ni

    2012-01-01

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS

  3. Mapping human whole-brain structural networks with diffusion MRI.

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    Patric Hagmann

    Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

  4. Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram

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    Batra, Marion; Nägele, Thomas

    2015-01-01

    Purpose. The distribution of apparent diffusion coefficient (ADC) values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Methods. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. Results. A consistent fitting of the histograms of all age groups was possible with the proposed model. Conclusions. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects. PMID:26609526

  5. Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram

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    Uwe Klose

    2015-01-01

    Full Text Available Purpose. The distribution of apparent diffusion coefficient (ADC values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Methods. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. Results. A consistent fitting of the histograms of all age groups was possible with the proposed model. Conclusions. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects.

  6. High-resolution whole-brain diffusion MRI at 7T using radiofrequency parallel transmission.

    Science.gov (United States)

    Wu, Xiaoping; Auerbach, Edward J; Vu, An T; Moeller, Steen; Lenglet, Christophe; Schmitter, Sebastian; Van de Moortele, Pierre-François; Yacoub, Essa; Uğurbil, Kâmil

    2018-03-30

    Investigating the utility of RF parallel transmission (pTx) for Human Connectome Project (HCP)-style whole-brain diffusion MRI (dMRI) data at 7 Tesla (7T). Healthy subjects were scanned in pTx and single-transmit (1Tx) modes. Multiband (MB), single-spoke pTx pulses were designed to image sagittal slices. HCP-style dMRI data (i.e., 1.05-mm resolutions, MB2, b-values = 1000/2000 s/mm 2 , 286 images and 40-min scan) and data with higher accelerations (MB3 and MB4) were acquired with pTx. pTx significantly improved flip-angle detected signal uniformity across the brain, yielding ∼19% increase in temporal SNR (tSNR) averaged over the brain relative to 1Tx. This allowed significantly enhanced estimation of multiple fiber orientations (with ∼21% decrease in dispersion) in HCP-style 7T dMRI datasets. Additionally, pTx pulses achieved substantially lower power deposition, permitting higher accelerations, enabling collection of the same data in 2/3 and 1/2 the scan time or of more data in the same scan time. pTx provides a solution to two major limitations for slice-accelerated high-resolution whole-brain dMRI at 7T; it improves flip-angle uniformity, and enables higher slice acceleration relative to current state-of-the-art. As such, pTx provides significant advantages for rapid acquisition of high-quality, high-resolution truly whole-brain dMRI data. © 2018 International Society for Magnetic Resonance in Medicine.

  7. Whole-brain diffusion-tensor changes in parkinsonian patients with impulse control disorders.

    Science.gov (United States)

    Yoo, Hye Bin; Lee, Jee-Young; Lee, Jae Sung; Kang, Hyejin; Kim, Yu Kyeong; Song, In Chan; Lee, Dong Soo; Jeon, Beom Seok

    2015-01-01

    The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson's disease (PD) patients undergoing chronic dopamine-replacement therapy. Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson's Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed. In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions. The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.

  8. In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

    International Nuclear Information System (INIS)

    Qin, Yuan-Yuan; Li, Mu-Wei; Oishi, Kenichi; Zhang, Shun; Zhang, Yan; Zhao, Ling-Yun; Zhu, Wen-Zhen; Lei, Hao

    2013-01-01

    Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the feasibility of applying whole-brain analysis methods to the investigation of an AD mouse model. (orig.)

  9. Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

    Science.gov (United States)

    Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

    2016-12-01

    Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

  10. Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI

    NARCIS (Netherlands)

    Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

    Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which

  11. Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach.

    Science.gov (United States)

    Roldan-Valadez, Ernesto; Rios, Camilo; Cortez-Conradis, David; Favila, Rafael; Moreno-Jimenez, Sergio

    2014-06-01

    Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks' λ = 0.324, χ(2) (3) = 38.907, p tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

  12. Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

    Science.gov (United States)

    He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

    2011-01-01

    The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

  13. In vivo quantitative whole-brain diffusion tensor imaging analysis of APP/PS1 transgenic mice using voxel-based and atlas-based methods

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    Qin, Yuan-Yuan [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Li, Mu-Wei; Oishi, Kenichi [The Johns Hopkins University School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Zhang, Shun; Zhang, Yan; Zhao, Ling-Yun; Zhu, Wen-Zhen [Huazhong University of Science and Technology, Department of Radiology, Tongji Hospital, Tongji Medical College, Wuhan (China); Lei, Hao [Chinese Academy of Sciences, Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Wuhan (China)

    2013-08-15

    Diffusion tensor imaging (DTI) has been applied to characterize the pathological features of Alzheimer's disease (AD) in a mouse model, although little is known about whether these features are structure specific. Voxel-based analysis (VBA) and atlas-based analysis (ABA) are good complementary tools for whole-brain DTI analysis. The purpose of this study was to identify the spatial localization of disease-related pathology in an AD mouse model. VBA and ABA quantification were used for the whole-brain DTI analysis of nine APP/PS1 mice and wild-type (WT) controls. Multiple scalar measurements, including fractional anisotropy (FA), trace, axial diffusivity (DA), and radial diffusivity (DR), were investigated to capture the various types of pathology. The accuracy of the image transformation applied for VBA and ABA was evaluated by comparing manual and atlas-based structure delineation using kappa statistics. Following the MR examination, the brains of the animals were analyzed for microscopy. Extensive anatomical alterations were identified in APP/PS1 mice, in both the gray matter areas (neocortex, hippocampus, caudate putamen, thalamus, hypothalamus, claustrum, amygdala, and piriform cortex) and the white matter areas (corpus callosum/external capsule, cingulum, septum, internal capsule, fimbria, and optic tract), evidenced by an increase in FA or DA, or both, compared to WT mice (p < 0.05, corrected). The average kappa value between manual and atlas-based structure delineation was approximately 0.8, and there was no significant difference between APP/PS1 and WT mice (p > 0.05). The histopathological changes in the gray matter areas were confirmed by microscopy studies. DTI did, however, demonstrate significant changes in white matter areas, where the difference was not apparent by qualitative observation of a single-slice histological specimen. This study demonstrated the structure-specific nature of pathological changes in APP/PS1 mouse, and also showed the

  14. Microstructural changes of whole brain in patients with comitant strabismus: evidence from a diffusion tensor imaging study

    Directory of Open Access Journals (Sweden)

    Huang X

    2016-08-01

    Full Text Available Xin Huang,1,2,* Hai-Jun Li,3,* Ying Zhang,1 De-Chang Peng,3 Pei-Hong Hu,1 Yu-Lin Zhong,1 Fu-Qing Zhou,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 2Department of Ophthalmology, The First People’s Hospital of Jiujiang City, Jiujiang, 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this work Objective: The aim of this study was to investigate the fractional anisotropy (FA and mean diffusivity (MD using a diffusion tensor imaging technique and whole-brain voxel-based analysis in patients with comitant strabismus.Patients and methods: A total of 19 (nine males and ten females patients with comitant strabismus and 19 age-, sex-, and education-matched healthy controls (HCs underwent magnetic resonance imaging examination. Imaging data were analyzed using two-sample t-tests to identify group differences in FA and MD values. Patients with comitant strabismus were distinguishable from HCs by receiver operating characteristic curves.Results: Compared with HCs, patients with comitant strabismus exhibited significantly decreased FA values in the brain regions of the left superior temporal gyrus and increased values in the bilateral medial frontal gyrus, right globus pallidus/brainstem, and bilateral precuneus. Meanwhile, MD value was significantly reduced in the brain regions of the bilateral cerebellum posterior lobe and left middle frontal gyrus but increased in the brain regions of the right middle frontal gyrus and left anterior cingulate.Conclusion: These results suggest significant brain abnormalities in comitant strabismus, which may underlie the pathologic mechanisms of fusion defects and ocular motility disorders in patients with comitant strabismus. Keywords: comitant strabismus, diffusion tensor imaging, mean diffusivity, fractional anisotropy, resting state

  15. Connectivity-based fixel enhancement: Whole-brain statistical analysis of diffusion MRI measures in the presence of crossing fibres

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    Raffelt, David A.; Smith, Robert E.; Ridgway, Gerard R.; Tournier, J-Donald; Vaughan, David N.; Rose, Stephen; Henderson, Robert; Connelly, Alan

    2015-01-01

    In brain regions containing crossing fibre bundles, voxel-average diffusion MRI measures such as fractional anisotropy (FA) are difficult to interpret, and lack within-voxel single fibre population specificity. Recent work has focused on the development of more interpretable quantitative measures that can be associated with a specific fibre population within a voxel containing crossing fibres (herein we use fixel to refer to a specific fibre population within a single voxel). Unfortunately, traditional 3D methods for smoothing and cluster-based statistical inference cannot be used for voxel-based analysis of these measures, since the local neighbourhood for smoothing and cluster formation can be ambiguous when adjacent voxels may have different numbers of fixels, or ill-defined when they belong to different tracts. Here we introduce a novel statistical method to perform whole-brain fixel-based analysis called connectivity-based fixel enhancement (CFE). CFE uses probabilistic tractography to identify structurally connected fixels that are likely to share underlying anatomy and pathology. Probabilistic connectivity information is then used for tract-specific smoothing (prior to the statistical analysis) and enhancement of the statistical map (using a threshold-free cluster enhancement-like approach). To investigate the characteristics of the CFE method, we assessed sensitivity and specificity using a large number of combinations of CFE enhancement parameters and smoothing extents, using simulated pathology generated with a range of test-statistic signal-to-noise ratios in five different white matter regions (chosen to cover a broad range of fibre bundle features). The results suggest that CFE input parameters are relatively insensitive to the characteristics of the simulated pathology. We therefore recommend a single set of CFE parameters that should give near optimal results in future studies where the group effect is unknown. We then demonstrate the proposed method

  16. Altered whole-brain connectivity in albinism.

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    Welton, Thomas; Ather, Sarim; Proudlock, Frank A; Gottlob, Irene; Dineen, Robert A

    2017-02-01

    Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. MR diffusion tensor imaging voxel-based analysis of whole brain white matter in patients with amnestic-type mild cognitive impairment and mild Alzheimer disease

    International Nuclear Information System (INIS)

    Li Yadi; Feng Xiaoyuan; He Huijin; Ding Ding; Tang Weijun; Zhao Qianhua

    2011-01-01

    correlation between FA value of WM in patient groups and Mini-Mental State Examination (MMSE) scores. Conclusions: Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD. The difference between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in early- stage AD were caused by multiple mechanisms. FA did not vary significantly in patients progressing from aMCI to mild AD and can hardly reflect the severity of cognitive function. damage in these patients. (authors)

  18. The whole brain diffusion tensor imaging study on acute phase of the posttraumatic stress disorder resulting from the single-prolonged stress based on tract based spatial statistics

    International Nuclear Information System (INIS)

    Xi Yibin; Liu Kang; Zhe Xia; Mu Yunfeng; Yin Hong; Huan Yi; Yang Xiaobin; Du Ping

    2013-01-01

    Objective: To study the changes of the brain white matter microstructure at the acute stage of posttraumatic stress disorder (PTSD) resulting from a single-prolonged stress. Methods: DTI scans were performed on 17 survivors buried more than 190 h in Shanxi Wangjialing mine disaster and 17 cases of normal controls using Siemens 3.0 T MR. The differences of the FA values measured from the whole brain DTI between the two groups were analyzed based on tract based spatial statistics (TBSS). FA data were statistically compared between the two groups based on nonparametric random permutation test (RPT), and the brain areas of the PTSD patients with abnormal FA were defined. Results: Compared with control group, FA values in the PTSD (at acute stage) group decreased in genu, rostral body of corpus callosum, and increased in the left thalamic and corticospinal tract region of bilateral corona radiata and the posterior limb of the left internal capsule, the left cerebral peduncle. The differences were statistically significant (P < 0.01 TFCE-corrected). Conclusions: TBSS is a comprehensive and accurate method for evaluating the changes of whole brain DTI in PTSD cases. The fiber structural abnormalities in the genu, rostral body of bilateral corpus callosum, anterior radiation of left thalamic may be due to stress. TBSS can provide a more objective basis for the early diagnosis and intervention of PTSD. (authors)

  19. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage irradiation was carried out on three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvementat and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20-26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. An exposure to 6000 rads, in a six weeks course, caused small, less than 1 mm, widely scattered necrotic lesions with a predilection for the forebrain white matter but not excluding the central gray matter and brain stem, at 26 weeks. At 52 weeks, there was considerable mineralization of the lesions and widespread telangiectasia. In the developing lesions, multiple minute breaks in the blood brain barrier caused diffuse brain swelling, reflected by papilloedema. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  20. Diffusion Tensor Magnetic Resonance Imaging Finding of Discrepant Fractional Anisotropy Between the Frontal and Parietal Lobes After Whole-Brain Irradiation in Childhood Medulloblastoma Survivors: Reflection of Regional White Matter Radiosensitivity?

    International Nuclear Information System (INIS)

    Qiu Deqiang; Kwong, Dora; Chan, Godfrey; Leung, Lucullus; Khong, P.-L.

    2007-01-01

    Purpose: To test the hypothesis that fractional anisotropy (FA) is more severely reduced in white matter of the frontal lobe compared with the parietal lobe after receiving the same whole-brain irradiation dose in a cohort of childhood medulloblastoma survivors. Methods and Materials: Twenty-two medulloblastoma survivors (15 male, mean [± SD] age = 12.1 ± 4.6 years) and the same number of control subjects (15 male, aged 12.0 ± 4.2 years) were recruited for diffusion tensor magnetic resonance imaging scans. Using an automated tissue classification method and the Talairach Daemon atlas, FA values of frontal and parietal lobes receiving the same radiation dose, and the ratio between them were quantified and denoted as FFA, PFA, and FA f/p , respectively. The Mann-Whitney U test was used to test for significant differences of FFA, PFA, and FA f/p between medulloblastoma survivors and control subjects. Results: Frontal lobe and parietal lobe white matter FA were found to be significantly less in medulloblastoma survivors compared with control subjects (frontal p = 0.001, parietal p = 0.026). Moreover, these differences were found to be discrepant, with the frontal lobe having a significantly larger difference in FA compared with the parietal lobe. The FA f/p of control and medulloblastoma survivors was 1.110 and 1.082, respectively (p = 0.029). Conclusion: Discrepant FA changes after the same irradiation dose suggest radiosensitivity of the frontal lobe white matter compared with the parietal lobe. Special efforts to address the potentially vulnerable frontal lobe after treatment with whole-brain radiation may be needed so as to balance disease control and treatment-related morbidity

  1. Whole-brain voxel-based morphometry of white matter in medial temporal lobe epilepsy

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    Yu Aihong [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053 (China); Li Kuncheng [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053 (China)], E-mail: Likuncheng@vip.sina.com; Li Lin; Shan Baoci [Institute of High Energy Physics, Chinese Academy of Sciences (China); Wang Yuping; Xue Sufang [Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences (China)

    2008-01-15

    Purpose: The purpose of this study was to analyze whole-brain white matter changes in medial temporal lobe epilepsy (MTLE). Materials and methods: We studied 23 patients with MTLE and 13 age- and sex-matched healthy control subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The seizure focus was right sided in 11 patients and left sided in 12. The data were collected on a 1.5 T MR system and analyzed by SPM 99 to generate white matter density maps. Results: Voxel-based morphometry revealed diffusively reduced white matter in MTLE prominently including bilateral frontal lobes, bilateral temporal lobes and corpus callosum. White matter reduction was also found in the bilateral cerebellar hemispheres in the left MTLE group. Conclusion: VBM is a simple and automated approach that is able to identify diffuse whole-brain white matter reduction in MTLE.

  2. Whole-brain voxel-based morphometry of white matter in medial temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Yu Aihong; Li Kuncheng; Li Lin; Shan Baoci; Wang Yuping; Xue Sufang

    2008-01-01

    Purpose: The purpose of this study was to analyze whole-brain white matter changes in medial temporal lobe epilepsy (MTLE). Materials and methods: We studied 23 patients with MTLE and 13 age- and sex-matched healthy control subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The seizure focus was right sided in 11 patients and left sided in 12. The data were collected on a 1.5 T MR system and analyzed by SPM 99 to generate white matter density maps. Results: Voxel-based morphometry revealed diffusively reduced white matter in MTLE prominently including bilateral frontal lobes, bilateral temporal lobes and corpus callosum. White matter reduction was also found in the bilateral cerebellar hemispheres in the left MTLE group. Conclusion: VBM is a simple and automated approach that is able to identify diffuse whole-brain white matter reduction in MTLE

  3. Whole-brain functional connectivity predicted by indirect structural connections

    DEFF Research Database (Denmark)

    Røge, Rasmus; Ambrosen, Karen Marie Sandø; Albers, Kristoffer Jon

    2017-01-01

    Modern functional and diffusion magnetic resonance imaging (fMRI and dMRI) provide data from which macro-scale networks of functional and structural whole brain connectivity can be estimated. Although networks derived from these two modalities describe different properties of the human brain, the...

  4. Whole-brain voxel-based morphometry of white matter in mild cognitive impairment

    International Nuclear Information System (INIS)

    Wang Zhiqun; Guo Xiaojuan; Qi Zhigang; Yao Li; Li Kuncheng

    2010-01-01

    Purpose: The purpose of this study was to analyze whole-brain white matter changes in mild cognitive impairment (MCI). Materials and methods: We studied 14 patients with MCI and 14 age- and sex-matched healthy control subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The data were collected on a 3T MR system and analyzed by SPM2 to generate white matter volume maps. Results: Voxel-based morphometry revealed diffusively reduced white matter in MCI prominently including the bilateral temporal gyrus, the right anterior cingulate, the bilateral superior and medial frontal gyrus and right parietal angular gyrus. White matter reduction was more prominent in anterior regions than that in posterior regions. Conclusion: Whole-brain white matter reduction in MCI patients detected with VBM has special distribution which is in line with the white matter pathology of MCI.

  5. Whole-brain voxel-based morphometry of white matter in mild cognitive impairment

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhiqun [Department of Radiology, Xuanwu Hospital of Capital Medical University, 100053, Beijing (China); Guo Xiaojuan [College of Information Science and Technology, Beijing Normal University, 100875, Beijing (China); National Key Laboratory for Cognitive Neuroscience and Learning, Beijing Normal University, 100875, Beijing (China); Qi Zhigang [Department of Radiology, Xuanwu Hospital of Capital Medical University, 100053, Beijing (China); Yao Li [College of Information Science and Technology, Beijing Normal University, 100875, Beijing (China); National Key Laboratory for Cognitive Neuroscience and Learning, Beijing Normal University, 100875, Beijing (China); Li Kuncheng, E-mail: likuncheng@xwh.ccmu.edu.c [Department of Radiology, Xuanwu Hospital of Capital Medical University, 100053, Beijing (China)

    2010-08-15

    Purpose: The purpose of this study was to analyze whole-brain white matter changes in mild cognitive impairment (MCI). Materials and methods: We studied 14 patients with MCI and 14 age- and sex-matched healthy control subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The data were collected on a 3T MR system and analyzed by SPM2 to generate white matter volume maps. Results: Voxel-based morphometry revealed diffusively reduced white matter in MCI prominently including the bilateral temporal gyrus, the right anterior cingulate, the bilateral superior and medial frontal gyrus and right parietal angular gyrus. White matter reduction was more prominent in anterior regions than that in posterior regions. Conclusion: Whole-brain white matter reduction in MCI patients detected with VBM has special distribution which is in line with the white matter pathology of MCI.

  6. Association between the scores of the Japanese version of the Brief Assessment of Cognition in Schizophrenia and whole-brain structure in patients with chronic schizophrenia: A voxel-based morphometry and diffusion tensor imaging study.

    Science.gov (United States)

    Hidese, Shinsuke; Ota, Miho; Matsuo, Junko; Ishida, Ikki; Hiraishi, Moeko; Teraishi, Toshiya; Hattori, Kotaro; Kunugi, Hiroshi

    2017-12-01

    The Brief Assessment of Cognition in Schizophrenia (BACS) is a concise tool designed to evaluate cognitive deficits in schizophrenia. We examined the possible association between BACS scores and whole-brain structure, as observed using magnetic resonance imaging with a relatively large sample. The study sample comprised 116 patients with schizophrenia (mean age, 39.3 ± 11.1 years; 66 men) and 118 healthy controls (HC; mean age, 40.0 ± 13.6 years; 58 men) who completed the Japanese version of the BACS (BACS-J). All participants were of Japanese ethnicity. The magnetic resonance imaging volume and diffusion tensor imaging data were processed with voxel-based morphometry and tract-based spatial statistics, respectively. There were significant reductions in the regional gray matter volumes and white matter fractional anisotropy values in patients with schizophrenia compared to HC. For the gray matter areas, the working memory score had a significant positive correlation with the anterior cingulate and medial frontal cortices volumes in the patients. For the white matter areas, the motor speed score had a significant positive correlation with fractional anisotropy values in the corpus callosum, internal capsule, superior corona radiata, and superior longitudinal fasciculus in the patients. However, there was no significant correlation among either the gray or white matter areas in the HC. Our results suggest that among the BACS-J measures, the working memory and motor speed scores are associated with several structural alterations in the brains of patients with schizophrenia. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  7. Bayesian Modelling of Functional Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Røge, Rasmus

    the prevalent strategy of standardizing of fMRI time series and model data using directional statistics or we model the variability in the signal across the brain and across multiple subjects. In either case, we use Bayesian nonparametric modeling to automatically learn from the fMRI data the number......This thesis deals with parcellation of whole-brain functional magnetic resonance imaging (fMRI) using Bayesian inference with mixture models tailored to the fMRI data. In the three included papers and manuscripts, we analyze two different approaches to modeling fMRI signal; either we accept...... of funcional units, i.e. parcels. We benchmark the proposed mixture models against state of the art methods of brain parcellation, both probabilistic and non-probabilistic. The time series of each voxel are most often standardized using z-scoring which projects the time series data onto a hypersphere...

  8. Concurrent whole brain radiotherapy and bortezomib for brain metastasis

    International Nuclear Information System (INIS)

    Lao, Christopher D; Hamstra, Daniel; Lawrence, Theodore; Hayman, James; Redman, Bruce G; Friedman, Judah; Tsien, Christina I; Normolle, Daniel P; Chapman, Christopher; Cao, Yue; Lee, Oliver; Schipper, Matt; Van Poznak, Catherine

    2013-01-01

    Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m 2 ) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m 2 /dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment

  9. Late effects of whole brain irradiation within the therapeutic range

    International Nuclear Information System (INIS)

    Caveness, W.F.; Carsten, A.L.

    1978-01-01

    Whole brain exposure with supervoltage x irradiation was carried out in three sets of Macaca mulatta. Two sets of 12 monkeys each, at puberty, received single and fractionated exposures, respectively. One set of 21 monkeys in adulthood received a fractionated exposure. Exposure to 1000 rads in a single dose, at puberty, caused no late effects. Exposure to 1500 rads caused small areas of necrosis in the forebrain white matter at 26 weeks, but a much more extensive involvement at and beyond 52 weeks that included confluent areas of necrosis in gray and white matter. Brain loss resulted in ventricular dilatation. Gliomas appeared in two out of three monkeys at or beyond 52 weeks. Exposure to 2000 rads caused such a wide scatter of focal areas of necrosis, including those in the brain stem, that survival beyond 20 to 26 weeks was not possible. All showed enlarged ventricular systems. Whole brain exposure, 200 rads a day, five days a week, for a course of 4000 rads, at puberty, resulted in no delayed effects. Whole brain exposure to 6000 rads in a six weeks course, in the adult, produced less effects than the same dose at puberty. The onset of the scattered necrotic lesions was later than expected, appearing in one out of three animals at 33 weeks, two out of three animals at 52 weeks, and two out of three at 104 weeks. The lesions at 104 weeks were predominantly mineralized, but were accompanied by a greater extent of telangiectasia than seen in the pubescent monkeys

  10. Whole-brain dynamic CT angiography and perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Orrison, W.W. [CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Department of Medical Education, University of Nevada School of Medicine, Reno, NV (United States); Snyder, K.V.; Hopkins, L.N. [Department of Neurosurgery, Millard Fillmore Gates Circle Hospital, Buffalo, NY (United States); Roach, C.J. [School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); Ringdahl, E.N. [Department of Psychology, University of Nevada Las Vegas, Las Vegas, NV (United States); Nazir, R. [Shifa International Hospital, Islamabad (Pakistan); Hanson, E.H., E-mail: eric.hanson@amigenics.co [College of Osteopathic Medicine, Touro University Nevada, Henderson, NV (United States); Department of Health Physics and Diagnostic Sciences, University of Nevada Las Vegas, Las Vegas, NV (United States); Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States)

    2011-06-15

    The availability of whole brain computed tomography (CT) perfusion has expanded the opportunities for analysing the haemodynamic parameters associated with varied neurological conditions. Examples demonstrating the clinical utility of whole-brain CT perfusion imaging in selected acute and chronic ischaemic arterial neurovascular conditions are presented. Whole-brain CT perfusion enables the detection and focused haemodynamic analyses of acute and chronic arterial conditions in the central nervous system without the limitation of partial anatomical coverage of the brain.

  11. Hypothalamic dysfunction following whole-brain irradiation

    International Nuclear Information System (INIS)

    Mechanick, J.I.; Hochberg, F.H.; LaRocque, A.

    1986-01-01

    The authors describe 15 cases with evidence of hypothalamic dysfunction 2 to 9 years following megavoltage whole-brain x-irradiation for primary glial neoplasm. The patients received 4000 to 5000 rads in 180- to 200-rad fractions. Dysfunction occurred in the absence of computerized tomography-delineated radiation necrosis or hypothalamic invasion by tumor, and antedated the onset of dementia. Fourteen patients displayed symptoms reflecting disturbances of personality, libido, thirst, appetite, or sleep. Hyperprolactinemia (with prolactin levels up to 70 ng/ml) was present in all of the nine patients so tested. Of seven patients tested with thyrotropin-releasing hormone, one demonstrated an abnormal pituitary gland response consistent with a hypothalamic disorder. Seven patients developed cognitive abnormalities. Computerized tomography scans performed a median of 4 years after tumor diagnosis revealed no hypothalamic tumor or diminished density of the hypothalamus. Cortical atrophy was present in 50% of cases and third ventricular dilatation in 58%. Hypothalamic dysfunction, heralded by endocrine, behavioral, and cognitive impairment, represents a common, subtle form of radiation damage

  12. A Thomistic defense of whole-brain death.

    Science.gov (United States)

    Eberl, Jason T

    2015-08-01

    Michel Accad critiques the currently accepted whole-brain criterion for determining the death of a human being from a Thomistic metaphysical perspective and, in so doing, raises objections to a particular argument defending the whole-brain criterion by Patrick Lee and Germain Grisez. In this paper, I will respond to Accad's critique of the whole-brain criterion and defend its continued validity as a criterion for determining when a human being's death has occurred in accord with Thomistic metaphysical principles. I will, however, join Accad in criticizing Lee and Grisez's proposed defense of the whole-brain criterion as potentially leading to erroneous conclusions regarding the determination of human death. Lay summary: Catholic physicians and bioethicists currently debate the legally accepted clinical standard for determining when a human being has died-known as the "wholebrain criterion"-which has also been morally affirmed by the Magisterium. This paper responds to physician Michel Accad's critique of the whole-brain criterion based upon St. Thomas Aquinas's metaphysical account of human nature as a union of a rational soul and a material body. I defend the whole-brain criterion from the same Thomistic philosophical perspective, while agreeing with Accad's objection to an alternative Thomistic defense of whole-brain death by philosophers Patrick Lee and Germain Grisez.

  13. MODEL OF THE TOKAMAK EDGE DENSITY PEDESTAL INCLUDING DIFFUSIVE NEUTRALS

    International Nuclear Information System (INIS)

    BURRELL, K.H.

    2003-01-01

    OAK-B135 Several previous analytic models of the tokamak edge density pedestal have been based on diffusive transport of plasma plus free-streaming of neutrals. This latter neutral model includes only the effect of ionization and neglects charge exchange. The present work models the edge density pedestal using diffusive transport for both the plasma and the neutrals. In contrast to the free-streaming model, a diffusion model for the neutrals includes the effect of both charge exchange and ionization and is valid when charge exchange is the dominant interaction. Surprisingly, the functional forms for the electron and neutral density profiles from the present calculation are identical to the results of the previous analytic models. There are some differences in the detailed definition of various parameters in the solution. For experimentally relevant cases where ionization and charge exchange rate are comparable, both models predict approximately the same width for the edge density pedestal

  14. Whole brain radiotherapy for brain metastases: The technique of irradiation influences the dose to parotid glands

    International Nuclear Information System (INIS)

    Loos, G.; Paulon, R.; Verrelle, P.; Lapeyre, M.

    2012-01-01

    In the treatment of brain metastases, whole brain radiotherapy can be carried out according two distinct methods: one using multi-leaf collimator for field shaping and protection of organs at risk, and a second one is to make a rotation of the field to avoid the eyes. The aim of the study was to compare for 10 patients the dose distributions at organs at risk for each method. Patients received 30 Gy in 10 fractions. Except for parotid glands, the dose received by organs at risk and the planning target volume was the same with each method. For whole brain radiotherapy, excluding the cisterna cerebellomedullaris, the mean parotid dose was 9.63 Gy using the multi-leaf collimator versus 12.32 Gy using the field rotation (P = 0.04). For whole brain radiotherapy including the cisterna cerebellomedullaris, the mean parotid dose was 11.12 Gy using the multi-leaf collimator versus 20.06 Gy using field rotation (P < 0.001). Using the multi-leaf collimator seems recommended for whole brain radiotherapy, to reduce the dose to the parotids. (authors)

  15. Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing

    International Nuclear Information System (INIS)

    Penitzka, S.; Wannenmacher, M.; Steinvorth, S.; MIT, Cambridge, MT; Sehlleier, S.; Universitaetsklinikum Wuerzburg; Fuss, M.; Texas Univ., San Antonio, TX; Wenz, F.; Universitaetsklinikum Mannheim

    2002-01-01

    Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [de

  16. Study of a diffusion flamelet model, with preferential diffusion effects included

    NARCIS (Netherlands)

    Delhaye, S.; Somers, L.M.T.; Bongers, H.; Oijen, van J.A.; Goey, de L.P.H.; Dias, V.

    2005-01-01

    The non-premixed flamelet model of Peters [1] (model1), which does not include preferential diffusion effects is investigated. Two similar models are presented, but without the assumption of unity Lewis numbers. One of these models was derived by Peters & Pitsch [2] (model2), while the other one was

  17. Development of a Model for Whole Brain Learning of Physiology

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-01-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed…

  18. Surgical Resection Followed by Whole Brain Radiotherapy Versus Whole Brain Radiotherapy Alone for Single Brain Metastasis

    International Nuclear Information System (INIS)

    Rades, Dirk; Kieckebusch, Susanne; Haatanen, Tiina; Lohynska, Radka; Dunst, Juergen; Schild, Steven E.

    2008-01-01

    Purpose: To compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis. Methods and Materials: The data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors. Results: On multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age ≤61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age ≤61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age ≤61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age ≤61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004). Conclusion: In patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control

  19. Explosive instabilities of reaction-diffusion equations including pinch effects

    International Nuclear Information System (INIS)

    Wilhelmsson, H.

    1992-01-01

    Particular solutions of reaction-diffusion equations for temperature are obtained for explosively unstable situations. As a result of the interplay between inertial, diffusion, pinch and source processes certain 'bell-shaped' distributions may grow explosively in time with preserved shape of the spatial distribution. The effect of the pinch, which requires a density inhomogeneity, is found to diminish the effect of diffusion, or inversely to support the inertial and source processes in creating the explosion. The results may be described in terms of elliptic integrals or. more simply, by means of expansions in the spatial coordinate. An application is the temperature evolution of a burning fusion plasma. (au) (18 refs.)

  20. Heat Diffusion in Gases, Including Effects of Chemical Reaction

    Science.gov (United States)

    Hansen, C. Frederick

    1960-01-01

    The diffusion of heat through gases is treated where the coefficients of thermal conductivity and diffusivity are functions of temperature. The diffusivity is taken proportional to the integral of thermal conductivity, where the gas is ideal, and is considered constant over the temperature interval in which a chemical reaction occurs. The heat diffusion equation is then solved numerically for a semi-infinite gas medium with constant initial and boundary conditions. These solutions are in a dimensionless form applicable to gases in general, and they are used, along with measured shock velocity and heat flux through a shock reflecting surface, to evaluate the integral of thermal conductivity for air up to 5000 degrees Kelvin. This integral has the properties of a heat flux potential and replaces temperature as the dependent variable for problems of heat diffusion in media with variable coefficients. Examples are given in which the heat flux at the stagnation region of blunt hypersonic bodies is expressed in terms of this potential.

  1. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

    International Nuclear Information System (INIS)

    Emmer, B.J.; Rijkee, M.; Walderveen, M.A.A. van; Niesten, J.M.; Velthuis, B.K.; Wermer, M.J.H.

    2014-01-01

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  2. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

    Energy Technology Data Exchange (ETDEWEB)

    Emmer, B.J. [Erasmus Medical Centre, Department of Radiology, Postbus 2040, Rotterdam (Netherlands); Rijkee, M.; Walderveen, M.A.A. van [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Niesten, J.M.; Velthuis, B.K. [University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Wermer, M.J.H. [Leiden University Medical Centre, Department of Neurology, Leiden (Netherlands)

    2014-12-15

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  3. Large Scale Computing for the Modelling of Whole Brain Connectivity

    DEFF Research Database (Denmark)

    Albers, Kristoffer Jon

    organization of the brain in continuously increasing resolution. From these images, networks of structural and functional connectivity can be constructed. Bayesian stochastic block modelling provides a prominent data-driven approach for uncovering the latent organization, by clustering the networks into groups...... of neurons. Relying on Markov Chain Monte Carlo (MCMC) simulations as the workhorse in Bayesian inference however poses significant computational challenges, especially when modelling networks at the scale and complexity supported by high-resolution whole-brain MRI. In this thesis, we present how to overcome...... these computational limitations and apply Bayesian stochastic block models for un-supervised data-driven clustering of whole-brain connectivity in full image resolution. We implement high-performance software that allows us to efficiently apply stochastic blockmodelling with MCMC sampling on large complex networks...

  4. An extended fractal growth regime in the diffusion limited aggregation including edge diffusion

    Directory of Open Access Journals (Sweden)

    Aritra Ghosh

    2016-01-01

    Full Text Available We have investigated on-lattice diffusion limited aggregation (DLA involving edge diffusion and compared the results with the standard DLA model. For both cases, we observe the existence of a crossover from the fractal to the compact regime as a function of sticking coefficient. However, our modified DLA model including edge diffusion shows an extended fractal growth regime like an earlier theoretical result using realistic growth models and physical parameters [Zhang et al., Phys. Rev. Lett. 73 (1994 1829]. While the results of Zhang et al. showed the existence of the extended fractal growth regime only on triangular but not on square lattices, we find its existence on the square lattice. There is experimental evidence of this growth regime on a square lattice. The standard DLA model cannot characterize fractal morphology as the fractal dimension (Hausdorff dimension, DH is insensitive to morphology. It also predicts DH = DP (the perimeter dimension. For the usual fractal structures, observed in growth experiments on surfaces, the perimeter dimension can differ significantly (DH ≠ DP depending on the morphology. Our modified DLA model shows minor sensitivity to this difference.

  5. Whole Brain Thinking : An Educational Alternative for Language Instructors

    OpenAIRE

    Ogawa,Ruby Toshimi

    2008-01-01

    Whole brain thinking offers new potentials in providing an educational alternative in teaching English as a Second Language (ESL). Prevailing research has shown that the right and the left sides of the brain function and process information differently according to Nobel Prize Winner Roger Sperry in his split-brain research on epileptics. While acknowledging these physical neurological differences, current research suggesting that in view of traditional teaching methods that rely on left-brai...

  6. Activating whole brain® innovation: A means of nourishing multiple intelligence in higher education

    Directory of Open Access Journals (Sweden)

    Ann-Louise De Boer

    2015-11-01

    Full Text Available The interconnectedness of the constructs ‘whole brain® thinking’ and ‘multiple intelligence’ forms the epicentre of this article. We depart from the premise that when whole brain® thinking is activated multiple intelligence can be nourished. When this becomes evident in a higher education practice it can be claimed that such a practice is innovative. Whole brain® thinking that informs intelligence and vice versa is inevitable when it comes to facilitating learning with a view to promoting quality learning in the context of higher education. If higher education is concerned about the expectations of industry and the world of work there is no other option as to prepare students in such a way that they develo as holistic – whole brained and intelligent – employers, employees and entrepreneurs who take responsibility for maximising their full potential. Becoming a self-regulated professional and being reflexive are some of the attributes of the 21st century which should be cultivated in all students. Research on whole brain® thinking and multiple intelligence shows that these human attributes form an integral part of one’s interaction with life – one’s environment and especially people as integral part of the environment. This focus on people highlights the need for developing soft skills within every curriculum. The epistemological underpinning of our reporting of experience in practice and research of the application of the principals of the constructs is meta- reflective in nature. Instead of a typical traditional stance to research we do not report on the numerous sets of data obtained over a period of more than 15 years. Our approach is that of a meta-reflective narrative as most of the studies we were involved in and still are, are reflective as it is most often than not action research-driven. And action research is a reflective process. We report on evidence-based practice that includes fields of specialisation such as

  7. White-matter microstructure and language lateralization in left-handers: a whole-brain MRI analysis.

    Science.gov (United States)

    Perlaki, Gabor; Horvath, Reka; Orsi, Gergely; Aradi, Mihaly; Auer, Tibor; Varga, Eszter; Kantor, Gyongyi; Altbäcker, Anna; John, Flora; Doczi, Tamas; Komoly, Samuel; Kovacs, Norbert; Schwarcz, Attila; Janszky, Jozsef

    2013-08-01

    Most people are left-hemisphere dominant for language. However the neuroanatomy of language lateralization is not fully understood. By combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), we studied whether language lateralization is associated with cerebral white-matter (WM) microstructure. Sixteen healthy, left-handed women aged 20-25 were included in the study. Left-handers were targeted in order to increase the chances of involving subjects with atypical language lateralization. Language lateralization was determined by fMRI using a verbal fluency paradigm. Tract-based spatial statistics analysis of DTI data was applied to test for WM microstructural correlates of language lateralization across the whole brain. Fractional anisotropy and mean diffusivity were used as indicators of WM microstructural organization. Right-hemispheric language dominance was associated with reduced microstructural integrity of the left superior longitudinal fasciculus and left-sided parietal lobe WM. In left-handed women, reduced integrity of the left-sided language related tracts may be closely linked to the development of right hemispheric language dominance. Our results may offer new insights into language lateralization and structure-function relationships in human language system. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Automated Whole Brain Tractography Affects Preoperative Surgical Decision Making.

    Science.gov (United States)

    Zakaria, Hesham; Haider, Sameah; Lee, Ian

    2017-09-06

    Surgery in and around eloquent brain structures poses a technical challenge when the goal of surgery is maximal safe resection. Magnetic resonance imaging (MRI) has revolutionized the diagnosis and treatment of neurological disorders, but tractography still remains limited in terms of utility because of the requisite manual labor and time required combined with the high risk of bias and inaccuracy. Automated whole brain tractography (AWBT) has simplified this workflow, overcoming historical barriers, and allowing for integration into modern neuronavigation. However, current literature showing the usefulness of this new technology is limited. In this study, we aimed to illustrate the utility of AWBT during cranial surgery and its ability to affect presurgical and intraoperative clinical decision making. We performed a retrospective chart review of cases that underwent AWBT for one year from July 2016 to July 2017. All patients underwent conventional anatomic MRI with and without contrast sequences, in addition to diffusion tensor imaging (DTI) on a 3 Tesla MRI scanner (Ingenia 3.0T, Philips, Amsterdam NL). Post-hoc AWBT processing was performed on a separate workstation. Patients were subsequently grouped into those that had undergone either language or motor mapping and those that did not. We compared both sets of patients to see any differences in patient age, sex, laterality of surgery, depth of resection from cortical surface, and smallest distance between the lesion and adjacent eloquent white matter tracts. We identified illustrative cases which demonstrated the ability of AWBT to affect surgical decision making. In this single-center series, we identified 73 total patients who underwent AWBT for intracranial surgery, of which 28 patients underwent either speech or language mapping. When comparing mapping to non-mapping patients, we found no difference with respect to age, gender, laterality of surgery, or whether the surgery was a revision. The distance

  9. Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection : A systematic review and meta-analysis

    NARCIS (Netherlands)

    Lamba, Nayan; Muskens, Ivo S; DiRisio, Aislyn C; Meijer, Louise; Briceno, Vanessa; Edrees, Heba; Aslam, Bilal; Minhas, Sadia; Verhoeff, Joost J.C.; Kleynen, Catharina E.; Smith, Timothy R; Mekary, Rania A; Broekman, Marike L.

    2017-01-01

    Background: In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative

  10. Multimodality 3D Superposition and Automated Whole Brain Tractography: Comprehensive Printing of the Functional Brain.

    Science.gov (United States)

    Konakondla, Sanjay; Brimley, Cameron J; Sublett, Jesna Mathew; Stefanowicz, Edward; Flora, Sarah; Mongelluzzo, Gino; Schirmer, Clemens M

    2017-09-29

    Whole brain tractography using diffusion tensor imaging (DTI) sequences can be used to map cerebral connectivity; however, this can be time-consuming due to the manual component of image manipulation required, calling for the need for a standardized, automated, and accurate fiber tracking protocol with automatic whole brain tractography (AWBT). Interpreting conventional two-dimensional (2D) images, such as computed tomography (CT) and magnetic resonance imaging (MRI), as an intraoperative three-dimensional (3D) environment is a difficult task with recognized inter-operator variability. Three-dimensional printing in neurosurgery has gained significant traction in the past decade, and as software, equipment, and practices become more refined, trainee education, surgical skills, research endeavors, innovation, patient education, and outcomes via valued care is projected to improve. We describe a novel multimodality 3D superposition (MMTS) technique, which fuses multiple imaging sequences alongside cerebral tractography into one patient-specific 3D printed model. Inferences on cost and improved outcomes fueled by encouraging patient engagement are explored.

  11. Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis.

    Science.gov (United States)

    Hong, Soon-Beom; Zalesky, Andrew; Fornito, Alex; Park, Subin; Yang, Young-Hui; Park, Min-Hyeon; Song, In-Chan; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bung-Nyun; Cho, Soo-Churl; Han, Doug Hyun; Cheong, Jae Hoon; Kim, Jae-Won

    2014-10-15

    Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD. A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Whole brain helical Tomotherapy with integrated boost for brain metastases in patients with malignant melanoma–a randomized trial

    International Nuclear Information System (INIS)

    Hauswald, Henrik; Habl, Gregor; Krug, David; Kehle, Denise; Combs, Stephanie E; Bermejo, Justo Lorenzo; Debus, Jürgen; Sterzing, Florian

    2013-01-01

    Patients with malignant melanoma may develop brain metastases during the course of the disease, requiring radiotherapeutic treatment. In patients with 1–3 brain metastases, radiosurgery has been established as a treatment option besides surgery. For patients with 4 or more brain metastases, whole brain radiotherapy is considered the standard treatment. In certain patients with brain metastases, radiation treatment using whole brain helical Tomotherapy with integrated boost and hippocampal-sparing may improve prognosis of these patients. The present prospective, randomized two-armed trial aims to exploratory investigate the treatment response to conventional whole brain radiotherapy applying 30 Gy in 10 fractions versus whole brain helical Tomotherapy applying 30 Gy in 10 fractions with an integrated boost of 50 Gy to the brain metastases as well as hippocampal-sparing in patients with brain metastases from malignant melanoma. The main inclusion criteria include magnetic resonance imaging confirmed brain metastases from a histopathologically confirmed malignant melanoma in patients with a minimum age of 18 years. The main exclusion criteria include a previous radiotherapy of the brain and not having recovered from acute high-grade toxicities of prior therapies. The primary endpoint is treatment-related toxicity. Secondary endpoints include imaging response, local and loco-regional progression-free survival, overall survival and quality of life

  13. Development of a model for whole brain learning of physiology.

    Science.gov (United States)

    Eagleton, Saramarie; Muller, Anton

    2011-12-01

    In this report, a model was developed for whole brain learning based on Curry's onion model. Curry described the effect of personality traits as the inner layer of learning, information-processing styles as the middle layer of learning, and environmental and instructional preferences as the outer layer of learning. The model that was developed elaborates on these layers by relating the personality traits central to learning to the different quadrants of brain preference, as described by Neethling's brain profile, as the inner layer of the onion. This layer is encircled by the learning styles that describe different information-processing preferences for each brain quadrant. For the middle layer, the different stages of Kolb's learning cycle are classified into the four brain quadrants associated with the different brain processing strategies within the information processing circle. Each of the stages of Kolb's learning cycle is also associated with a specific cognitive learning strategy. These two inner circles are enclosed by the circle representing the role of the environment and instruction on learning. It relates environmental factors that affect learning and distinguishes between face-to-face and technology-assisted learning. This model informs on the design of instructional interventions for physiology to encourage whole brain learning.

  14. Radiosurgery without whole brain radiotherapy in melanoma brain metastases

    International Nuclear Information System (INIS)

    Grob, J.J.; Regis, J.; Laurans, R.; Delaunay, M.; Wolkenstein, P.; Paul, K.; Souteyrand, P.; Koeppel, M.C.; Murraciole, X.; Perragut, J.C.; Bonerandi, J.J.

    1998-01-01

    To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

    International Nuclear Information System (INIS)

    Zhang Yuan; Sun Rui; Zhu Yaqun; Zhang Liyuan; Ji Jianfeng; Li Kun; Tian Ye

    2014-01-01

    Objective: To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods: Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group(C), swimming group(C-S), radiation group(R), and radiation plus swimming group(R-S). Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results: On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P 0.05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation (P < 0.05), but this reduction was attenuated by the chronic forced swimming stress. Conclusion: The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. (authors)

  16. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global – disturbed local network organization

    Directory of Open Access Journals (Sweden)

    Justina Sidlauskaite

    2015-01-01

    Full Text Available Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD. However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics — small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

  17. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

    Science.gov (United States)

    Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

    2015-01-01

    Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

  18. Whole brain imaging with Serial Two-Photon Tomography

    Directory of Open Access Journals (Sweden)

    Stephen P Amato

    2016-03-01

    Full Text Available Imaging entire mouse brains at submicron resolution has historically been a challenging undertaking and largely confined to the province of dedicated atlasing initiatives. The has limited systematic investigations into important areas of neuroscience, such as neural circuits, brain mapping and neurodegeneration. In this paper, we describe in detail Serial Two-Photon (STP tomography, a robust, reliable method for imaging entire brains with histological detail. We provide examples of how the basic methodology can be extended to other imaging modalities, such as optical coherence tomography, in order to provide unique contrast mechanisms. Furthermore we provide a survey of the research that STP tomography has enabled in the field of neuroscience, provide examples of how this technology enables quantitative whole brain studies, and discuss the current limitations of STP tomography-based approaches

  19. Hippocampus sparing in whole-brain radiotherapy. A review

    International Nuclear Information System (INIS)

    Oskan, F.; Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M.

    2014-01-01

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [de

  20. MRI assessment of whole-brain structural changes in aging.

    Science.gov (United States)

    Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

    2017-01-01

    One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P age ( r 2 >0.29; P 26.48, P aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.

  1. Cost-effective immobilization for whole brain radiation therapy.

    Science.gov (United States)

    Rubinstein, Ashley E; Ingram, W Scott; Anderson, Brian M; Gay, Skylar S; Fave, Xenia J; Ger, Rachel B; McCarroll, Rachel E; Owens, Constance A; Netherton, Tucker J; Kisling, Kelly D; Court, Laurence E; Yang, Jinzhong; Li, Yuting; Lee, Joonsang; Mackin, Dennis S; Cardenas, Carlos E

    2017-07-01

    To investigate the inter- and intra-fraction motion associated with the use of a low-cost tape immobilization technique as an alternative to thermoplastic immobilization masks for whole-brain treatments. The results of this study may be of interest to clinical staff with severely limited resources (e.g., in low-income countries) and also when treating patients who cannot tolerate standard immobilization masks. Setup reproducibility of eight healthy volunteers was assessed for two different immobilization techniques. (a) One strip of tape was placed across the volunteer's forehead and attached to the sides of the treatment table. (b) A second strip was added to the first, under the chin, and secured to the table above the volunteer's head. After initial positioning, anterior and lateral photographs were acquired. Volunteers were positioned five times with each technique to allow calculation of inter-fraction reproducibility measurements. To estimate intra-fraction reproducibility, 5-minute anterior and lateral videos were taken for each technique per volunteer. An in-house software was used to analyze the photos and videos to assess setup reproducibility. The maximum intra-fraction displacement for all volunteers was 2.8 mm. Intra-fraction motion increased with time on table. The maximum inter-fraction range of positions for all volunteers was 5.4 mm. The magnitude of inter-fraction and intra-fraction motion found using the "1-strip" and "2-strip" tape immobilization techniques was comparable to motion restrictions provided by a thermoplastic mask for whole-brain radiotherapy. The results suggest that tape-based immobilization techniques represent an economical and useful alternative to the thermoplastic mask. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  2. Hippocampus sparing in whole-brain radiotherapy. A review

    Energy Technology Data Exchange (ETDEWEB)

    Oskan, F. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany); Saarland University Medical Center, Department of Radiation Oncology, Homburg/Saar (Germany); Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany)

    2014-04-15

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [German] Die Technik der Ganzhirnbestrahlung (''whole-brain radiation therapy'', WBRT) hat sich seit der Entwicklung nicht wesentlich veraendert. Allerdings stellten die Neuentwicklung von Techniken wie die intensitaetsmodulierte Strahlentherapie (IMRT), die volumenmodulierte Arc-Therapie (VMAT) oder die helikale Tomotherapie sowie immer groesseres Wissen ueber das neurale Stammzellkompartiment (NSCs) das herkoemmliche Ganzhirn-Paradigma in Frage. Die hippocampusschonende Ganzhirnbestrahlung ist eine neuartige Technik, welche die kritische Region des Hippocampus schont, ohne die Tumorkontrolle zu gefaehrden. Ueber diese Technik gibt es bisher nur eine begrenzte Datenlage im Sinne von Planungs- und Machbarkeitsstudien. Klinische Daten bzgl. der Behandlungsergebnisse fehlen nach wie vor, aber einige prospektive Studien sind im Gange, um nicht nur die Machbarkeit zu belegen, sondern auch das klinische Outcome im Sinne einer verringerten Neurotoxizitaet nachzuweisen. (orig.)

  3. Time-efficient, high-resolution, whole brain three-dimensional macromolecular proton fraction mapping.

    Science.gov (United States)

    Yarnykh, Vasily L

    2016-05-01

    Macromolecular proton fraction (MPF) mapping is a quantitative MRI method that reconstructs parametric maps of a relative amount of macromolecular protons causing the magnetization transfer (MT) effect and provides a biomarker of myelination in neural tissues. This study aimed to develop a high-resolution whole brain MPF mapping technique using a minimal number of source images for scan time reduction. The described technique was based on replacement of an actually acquired reference image without MT saturation by a synthetic one reconstructed from R1 and proton density maps, thus requiring only three source images. This approach enabled whole brain three-dimensional MPF mapping with isotropic 1.25 × 1.25 × 1.25 mm(3) voxel size and a scan time of 20 min. The synthetic reference method was validated against standard MPF mapping with acquired reference images based on data from eight healthy subjects. Mean MPF values in segmented white and gray matter appeared in close agreement with no significant bias and small within-subject coefficients of variation (maps demonstrated sharp white-gray matter contrast and clear visualization of anatomical details, including gray matter structures with high iron content. The proposed synthetic reference method improves resolution of MPF mapping and combines accurate MPF measurements with unique neuroanatomical contrast features. © 2015 Wiley Periodicals, Inc.

  4. Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints.

    Directory of Open Access Journals (Sweden)

    Fang-Cheng Yeh

    2016-11-01

    Full Text Available Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213, we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.

  5. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuo, E-mail: shuo0220@gmail.com; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-04-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle{sup 3} Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle{sup 3} Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle{sup 3} Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D{sub 2%} and D{sub 98%} of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D{sub 100%} and D{sub max} of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle{sup 3} Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The

  6. Automatic planning on hippocampal avoidance whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Wang, Shuo; Zheng, Dandan; Zhang, Chi; Ma, Rongtao; Bennion, Nathan R.; Lei, Yu; Zhu, Xiaofeng; Enke, Charles A.; Zhou, Sumin

    2017-01-01

    Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle 3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle 3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle 3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D 2% and D 98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D 100% and D max of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle 3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by

  7. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-01-01

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  8. Whole-brain activity mapping onto a zebrafish brain atlas

    Science.gov (United States)

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  9. Whole-brain activity mapping onto a zebrafish brain atlas.

    Science.gov (United States)

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

  10. Whole-brain atrophy rate and cognitive decline: longitudinal MR study of memory clinic patients

    NARCIS (Netherlands)

    Sluimer, J.D.; van der Flier, W.M.; Karas, G.B.; Fox, N.C.; Scheltens, P.; Barkhof, F.; Vrenken, H.

    2008-01-01

    Purpose: To prospectively determine whole-brain atrophy rate in mild cognitive impairment (MCI) and Alzheimer disease (AD) and its association with cognitive decline, and investigate the risk of progression to dementia in initially non-demented patients given baseline brain volume and whole-brain

  11. Whole-brain radiation therapy for brain metastases: detrimental or beneficial?

    International Nuclear Information System (INIS)

    Gemici, Cengiz; Yaprak, Gokhan

    2015-01-01

    Stereotactic radiosurgery is frequently used, either alone or together with whole-brain radiation therapy to treat brain metastases from solid tumors. Certain experts and radiation oncology groups have proposed replacing whole-brain radiation therapy with stereotactic radiosurgery alone for the management of brain metastases. Although randomized trials have favored adding whole-brain radiation therapy to stereotactic radiosurgery for most end points, a recent meta-analysis demonstrated a survival disadvantage for patients treated with whole-brain radiation therapy and stereotactic radiosurgery compared with patients treated with stereotactic radiosurgery alone. However the apparent detrimental effect of adding whole-brain radiation therapy to stereotactic radiosurgery reported in this meta-analysis may be the result of inhomogeneous distribution of the patients with respect to tumor histologies, molecular histologic subtypes, and extracranial tumor stages between the groups rather than a real effect. Unfortunately, soon after this meta-analysis was published, even as an abstract, use of whole-brain radiation therapy in managing brain metastases has become controversial among radiation oncologists. The American Society of Radiation Oncology recently recommended, in their “Choose Wisely” campaign, against routinely adding whole-brain radiation therapy to stereotactic radiosurgery to treat brain metastases. However, this situation creates conflict for radiation oncologists who believe that there are enough high level of evidence for the effectiveness of whole-brain radiation therapy in the treatment of brain metastases

  12. Radiosurgery for brain metastases: is whole brain radiation therapy necessary?

    International Nuclear Information System (INIS)

    Forstner, Julie M.; Sneed, Penny K.; Lamborn, Kathleen R.; Shu, H.-K.G.; McDermott, Michael W.; Park, Elaine; Ho, Maria; Chang, Susan; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1996-01-01

    Purpose: Because whole brain radiotherapy (WBRT) carries a significant risk of dementia in long-term survivors, it is desirable to determine if some patients with brain metastases may be managed with radiosurgery (RS) alone, reserving WBRT for salvage therapy as needed. To begin to approach this problem, we retrospectively reviewed freedom from brain failure/progression (Brain FFP) and survival of patients with newly-diagnosed solitary or multiple brain metastases treated with Gamma Knife RS ± WBRT. Materials and Methods: All patients treated at our institution with Gamma Knife RS for newly-diagnosed solitary or multiple (2-8) brain metastases from September 1991 through December 1995 were reviewed. Whether or not WBRT was given depended on physician preference and referral patterns. Brain FFP was measured from the date of RS until development of a new brain metastasis or progression of a treated metastasis, with censoring at the time of the last imaging study. Survival was measured from the date of RS until death or last clinical follow-up. Actuarial curves were estimated using the Kaplan-Meier method and compared with the log rank test. Multivariate analyses to adjust for known prognostic variables (age, KPS, history of extracranial metastases, and total target volume) were performed using the Cox proportional hazards model. Results: From September 1991-December 1995, 90 patients with newly-diagnosed brain metastases underwent RS. Three patients treated palliatively to a small component of their intracranial disease were excluded, leaving 54 treated with RS alone and 33 treated with RS + WBRT. Age ranged from 31-83 years (median, 59 years), KPS from 60-100 (median, 90), and total target volume from 0.15-26.1 cm 3 (median, 5.5 cm 3 ). Fifty patients had a history of extracranial metastases. Results are shown below. In the RS alone group, (22(54)) patients (41%) had a brain failure and (20(54)) (37%) died without evidence of brain failure. In the RS + WBRT group

  13. The role of CT simulation in whole-brain irradiation

    International Nuclear Information System (INIS)

    Gripp, Stephan; Doeker, Rolf; Glag, Michael; Vogelsang, Petra; Bannach, Burckhardt; Doll, Thorsten; Muskalla, Klaus; Schmitt, Gerd

    1999-01-01

    Purpose: Evidence is growing that incorrect field-shaping is a major cause of treatment failure in whole-brain irradiation (WBI). To evaluate the potential benefits of CT simulation in WBI we compared field-shaping based on 3D CT simulation to conventional 2D simulation. Methods: CT head scans were obtained from 20 patients. Conventional 2D planning was imitated by drawing the block contours on digitally reconstructed radiographs (DRR) by four radiotherapists. Critical parts of the target and the eye lenses were subsequently marked and planning was repeated using 3D information ('3D planning'). The results of both methods were compared by evaluation of the minimal distance from the field edge according to each site. Results: In conventional planning using DRR, major geographic mismatches (< -3 mm) occurred in the subfrontal region and both eye lenses with 1% each location. Minor mismatches (-3 to 0 mm) predominantly occurred in the contralateral lens (21%), ipsilateral lens (10%), and subfrontal region (9%). Close margins (0-5 mm) were most frequently noted at the contralateral lens (49%), ipsilateral lens (35%), and the subfrontal region (28%). When 3D planning was used, mismatches were not found. However, close margins were inevitable at the ipsilateral lens (5%), subfrontal region (30%), and contralateral lens (70%). Conclusions: CT simulation in WBI is significantly superior to conventional simulation with respect to complete coverage of the target volume and protection of the eye lenses. The narrow passage between the ocular lenses and lamina cribrosa represents a serious limitation. These patients are safely identified with CT simulation and can be referred for modified irradiation techniques

  14. Radiosurgery for brain metastases: is whole brain radiotherapy necessary?

    International Nuclear Information System (INIS)

    Sneed, Penny K.; Lamborn, Kathleen R.; Forstner, Julie M.; McDermott, Michael W.; Chang, Susan; Park, Elaine; Gutin, Philip H.; Phillips, Theodore L.; Wara, William M.; Larson, David A.

    1999-01-01

    Purpose: Because whole brain radiotherapy (WBRT) may cause dementia in long-term survivors, selected patients with brain metastases may benefit from initial treatment with radiosurgery (RS) alone reserving WBRT for salvage as needed. We reviewed results of RS ± WBRT in patients with newly diagnosed brain metastasis to provide background for a prospective trial. Methods and Materials: Patients with single or multiple brain metastases managed initially with RS alone vs. RS + WBRT (62 vs. 43 patients) from 1991 through February 1997 were retrospectively reviewed. The use of upfront WBRT depended on physician preference and referral patterns. Survival, freedom from progression (FFP) endpoints, and brain control allowing for successful salvage therapy were measured from the date of diagnosis of brain metastases. Actuarial curves were estimated using the Kaplan-Meier method. Analyses to adjust for known prognostic factors were performed using the Cox proportional hazards model (CPHM) stratified by primary site. Results: Survival and local FFP were the same for RS alone vs. RS + WBRT (median survival 11.3 vs. 11.1 months and 1-year local FFP by patient 71% vs. 79%, respectively). Brain FFP (scoring new metastases and/or local failure) was significantly worse for RS alone vs. RS + WBRT (28% vs. 69% at 1 year; CPHM adjusted p = 0.03 and hazard ratio = 0.476). However, brain control allowing for successful salvage of a first failure was not significantly different for RS alone vs. RS + WBRT (62% vs. 73% at 1 year; CPHM adjusted p = 0.56). Conclusions: The omission of WBRT in the initial management of patients treated with RS for up to 4 brain metastases does not appear to compromise survival or intracranial control allowing for salvage therapy as indicated. A randomized trial of RS vs. RS + WBRT is needed to assess survival, quality of life, and cost in good-prognosis patients with newly diagnosed brain metastases

  15. Whole brain radiotherapy with radiosensitizer for brain metastases

    Directory of Open Access Journals (Sweden)

    Viani Gustavo

    2009-01-01

    Full Text Available Abstract Purpose To study the efficacy of whole brain radiotherapy (WBRT with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. Methods A meta-analysis of randomized controlled trials (RCT was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently. Results A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84–1.25, p = 0.77. Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 – 1.03 and brain tumor progression (OR = 1.11, 95% CI 0.9 – 1.3 when the two arms were compared. Conclusion Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide, have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

  16. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    International Nuclear Information System (INIS)

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  17. Non-kinematic Flux-transport Dynamos Including the Effects of Diffusivity Quenching

    Energy Technology Data Exchange (ETDEWEB)

    Ichimura, Chiaki; Yokoyama, Takaaki [Department of Earth and Planetary Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2017-04-10

    Turbulent magnetic diffusivity is quenched when strong magnetic fields suppress turbulent motion in a phenomenon known as diffusivity quenching. Diffusivity quenching can provide a mechanism for amplifying magnetic field and influencing global velocity fields through Lorentz force feedback. To investigate this effect, we conducted mean field flux-transport dynamo simulations that included the effects of diffusivity quenching in a non-kinematic regime. We found that toroidal magnetic field strength is amplified by up to approximately 1.5 times in the convection zone as a result of diffusivity quenching. This amplification is much weaker than that in kinematic cases as a result of Lorentz force feedback on the system’s differential rotation. While amplified toroidal fields lead to the suppression of equatorward meridional flow locally near the base of the convection zone, large-scale equatorward transport of magnetic flux via meridional flow, which is the essential process of the flux-transport dynamo, is sustainable in our calculations.

  18. Longitudinal Whole-Brain N-acetylaspartate Concentration in Healthy Adults

    Science.gov (United States)

    Rigotti, Daniel J.; Kirov, Ivan I.; Djavadi, Bejan; Perry, Nissa N.; Babb, James S.; Gonen, Oded

    2011-01-01

    BACKGROUND AND PURPOSE Though N-acetylaspartate (NAA) is often used as a marker of neural integrity and health in different neurological disorders, the temporal behavior of its whole-brain concentration (WBNAA) is not well characterized. Our goal, therefore, was to establish its normal variations in a cohort of healthy adults over typical clinical trial periods. METHODS Baseline amount of brain NAA, QNAA, was obtained with non-localizing proton MR spectroscopy from 9 subjects (7 women, 2 men) 31.2±5.6 years old. QNAA was converted into absolute millimole amount using phantom-replacement. The WBNAA concentration was derived by dividing QNAA with the brain parenchyma volume, VB, segmented from MRI. Temporal variations were determined with four annual scans of each participant. RESULTS The distribution of WBNAA levels was not different among time points with respect to the mean, 12.1±1.5 mM (p 0.6) nor was its intra-subject change (CV = 8.6%) significant between any two scans (p 0.5). There was a small (0.2 mL), but significant (p=0.05) annual VB decline. CONCLUSION WBNAA is stable over a three year period in healthy adults. It qualifies therefore, as a biomarker for global neuronal loss and dysfunction in diffuse neurological disorders that may be well worth considering as a secondary outcome measure candidate for clinical trials. PMID:21511862

  19. Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Robert J.; Jun, Brandon J. [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); Cushman, Jesse D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Harris, Neil G. [UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA Center for the Health Sciences, Los Angeles, California (United States); Jentsch, James D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Bluml, Stefan [Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); McBride, William H., E-mail: wmcbride@mednet.ucla.edu [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States)

    2016-10-01

    Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

  20. Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

    International Nuclear Information System (INIS)

    Brown, Robert J.; Jun, Brandon J.; Cushman, Jesse D.; Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe; Harris, Neil G.; Jentsch, James D.; Bluml, Stefan; McBride, William H.

    2016-01-01

    Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

  1. 78 FR 66779 - United States Enrichment Corporation, Paducah Gaseous Diffusion Plant, Including On-Site Leased...

    Science.gov (United States)

    2013-11-06

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,862] United States Enrichment..., applicable to workers of United States Enrichment Corporation, Paducah Gaseous Diffusion Plant, including on... were engaged in the production of low enrichment uranium. The company reports that workers leased from...

  2. A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

    Science.gov (United States)

    Yuan, Xi; Liu, Wen-Jie; Li, Bing; Shen, Ze-Tian; Shen, Jun-Shu; Zhu, Xi-Xu

    2017-08-01

    This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

  3. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  4. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

    Science.gov (United States)

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  5. Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

    Directory of Open Access Journals (Sweden)

    Rongfeng Hu

    2016-10-01

    Full Text Available The basal forebrain cholinergic system (BFCS robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum (LS, central amygdala (CeA, paraventricular nucleus of hypothalamus (PVH, dorsal raphe (DRN and parabrachial nucleus (PBN. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal-hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function.

  6. Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

    Science.gov (United States)

    Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

    2016-01-01

    Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  7. Whole-brain mapping of neuronal activity in the learned helplessness model of depression

    Directory of Open Access Journals (Sweden)

    Yongsoo eKim

    2016-02-01

    Full Text Available Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing helpless behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing resilient behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  8. Re-irradiation for metastatic brain tumors with whole-brain radiotherapy

    International Nuclear Information System (INIS)

    Akiba, Takeshi; Kunieda, Etsuo; Kogawa, Asuka; Komatsu, Tetsuya; Tamai, Yoshifumi; Ohizumi, Yukio

    2012-01-01

    The objective of this study was to determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P=0.003) and the Karnofsky performance status at the time of re-irradiation (P=0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P=0.050). Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. (author)

  9. Spatial patterns of whole brain grey and white matter injury in patients with occult spastic diplegic cerebral palsy.

    Science.gov (United States)

    Mu, Xuetao; Nie, Binbin; Wang, Hong; Duan, Shaofeng; Zhang, Zan; Dai, Guanghui; Ma, Qiaozhi; Shan, Baoci; Ma, Lin

    2014-01-01

    Spastic diplegic cerebral palsy (SDCP) is a common type of cerebral palsy (CP), which presents as a group of motor-impairment syndromes. Previous conventional MRI studies have reported abnormal structural changes in SDCP, such as periventricular leucomalacia. However, there are roughly 27.8% SDCP patients presenting normal appearance in conventional MRI, which were considered as occult SDCP. In this study, sixteen patients with occult SDCP and 16 age- and sex-matched healthy control subjects were collected and the data were acquired on a 3T MR system. We applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis to investigate whole brain grey and white matter injury in occult SDCP. By using VBM method, the grey matter volume reduction was revealed in the bilateral basal ganglia regions, thalamus, insula, and left cerebral peduncle, whereas the white matter atrophy was found to be located in the posterior part of corpus callosum and right posterior corona radiata in the occult SDCP patients. By using TBSS, reduced fractional anisotropy (FA) values were detected in multiple white matter regions, including bilateral white matter tracts in prefrontal lobe, temporal lobe, internal and external capsule, corpus callosum, cingulum, thalamus, brainstem and cerebellum. Additionally, several regions of white matter tracts injury were found to be significantly correlated with motor dysfunction. These results collectively revealed the spatial patterns of whole brain grey and white matter injury in occult SDCP.

  10. Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

    Directory of Open Access Journals (Sweden)

    Guihua Jiang

    Full Text Available Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs and 15 age-, gender-matched normal controls (NCs were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

  11. Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

    Science.gov (United States)

    Jiang, Guihua; Wen, Xue; Qiu, Yingwei; Zhang, Ruibin; Wang, Junjing; Li, Meng; Ma, Xiaofen; Tian, Junzhang; Huang, Ruiwang

    2013-01-01

    Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

  12. Nox diffusion-simulation in an urban area in using the vertical diffusion diagram including a surface roughness parameter

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Hitoshi; Fujimoto, Akira; Nakano, Hiroshi

    1988-03-31

    In recent years, in order to attain a total quantity regulation of air pollution and to prepare a local air-control program, a diffusion simulation is often made using a Gaussian plume model. NOx diffusion simulation of the urban area was carried out using a vertical diffusion width by taking a parameter of ground-surface roughness using Smith's correction to the Gaussian model. For the diffusion of car exhaust gas, comparison was made for the estimate and the measurement by jointly using the values of ground-surface roughness and the initial diffusion width. As a result, change in the diffusion width of the car exhaust gas due to the urban buildings was expressed at a necessary practical level by giving the height of the point of calculation, 1 - 3 m in the central part and 30 cm at the peripheral part, and giving the initial diffusion width of roughly half to equal size of initial diffusion width to the average height of the buildings. (2 figs, 8 tabs, 20 refs)

  13. Individualized prediction of schizophrenia based on the whole-brain pattern of altered white matter tract integrity.

    Science.gov (United States)

    Chen, Yu-Jen; Liu, Chih-Min; Hsu, Yung-Chin; Lo, Yu-Chun; Hwang, Tzung-Jeng; Hwu, Hai-Gwo; Lin, Yi-Tin; Tseng, Wen-Yih Isaac

    2018-01-01

    A schizophrenia diagnosis relies on characteristic symptoms identified by trained physicians, and is thus prone to subjectivity. This study developed a procedure for the individualized prediction of schizophrenia based on whole-brain patterns of altered white matter tract integrity. The study comprised training (108 patients and 144 controls) and testing (60 patients and 60 controls) groups. Male and female participants were comparable in each group and were analyzed separately. All participants underwent diffusion spectrum imaging of the head, and the data were analyzed using the tract-based automatic analysis method to generate a standardized two-dimensional array of white matter tract integrity, called the connectogram. Unique patterns in the connectogram that most accurately identified schizophrenia were systematically reviewed in the training group. Then, the diagnostic performance of the patterns was individually verified in the testing group by using receiver-operating characteristic curve analysis. The performance was high in men (accuracy = 0.85) and satisfactory in women (accuracy = 0.75). In men, the pattern was located in discrete fiber tracts, as has been consistently reported in the literature; by contrast, the pattern was widespread over all tracts in women. These distinct patterns suggest that there is a higher variability in the microstructural alterations in female patients than in male patients. The individualized prediction of schizophrenia is feasible based on the different whole-brain patterns of tract integrity. The optimal masks and their corresponding regions in the fiber tracts could serve as potential imaging biomarkers for schizophrenia. Hum Brain Mapp 39:575-587, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. The Effect of Herrmann Whole Brain Teaching Method on Students' Understanding of Simple Electric Circuits

    Science.gov (United States)

    Bawaneh, Ali Khalid Ali; Nurulazam Md Zain, Ahmad; Salmiza, Saleh

    2011-01-01

    The purpose of this study was to investigate the effect of Herrmann Whole Brain Teaching Method over conventional teaching method on eight graders in their understanding of simple electric circuits in Jordan. Participants (N = 273 students; M = 139, F = 134) were randomly selected from Bani Kenanah region-North of Jordan and randomly assigned to…

  15. Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

    Science.gov (United States)

    Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

    2018-02-01

    The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

  16. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M. [Johns Hopkins Hospital, Division of Pediatric Radiology, Department of Radiology and Radiological Science, Baltimore, MD (United States); Mitchell, Sally [Johns Hopkins Hospital, Division of Cardiovascular and Interventional Radiology, Department of Radiology and Radiological Science, Baltimore (United States); Keefer, Jeffrey [Johns Hopkins Hospital, Division of Pediatric Hematology, Department of Pediatrics, Baltimore, MD (United States)

    2009-10-15

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  17. Pediatric littoral cell angioma of the spleen: multimodality imaging including diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Ertan, Gulhan; Tekes, Aylin; Huisman, Thierry A.G.M.; Mitchell, Sally; Keefer, Jeffrey

    2009-01-01

    Littoral cell angioma (LCA) is a rare primary splenic vascular tumor originating from littoral cells lining the splenic red pulp sinuses. LCAs are rarely seen in children. We present the US, CT, and MRI findings including diffusion-weighted imaging (DWI) in a 2-year-old boy with histologically proven LCA. Previous studies on liver lesions have shown that DWI allows differentiation of vascular tumors from primary neoplasms and metastatic disease. The current case indicates that increased ADC values within the splenic lesions suggest a vascular etiology, which might help narrow the differential diagnosis. (orig.)

  18. Literature survey of matrix diffusion theory and of experiments and data including natural analogues

    International Nuclear Information System (INIS)

    Ohlsson, Yvonne; Neretnieks, I.

    1995-08-01

    Diffusion theory in general and matrix diffusion in particular has been outlined, and experimental work has been reviewed. Literature diffusion data has been systematized in the form of tables and data has been compared and discussed. Strong indications of surface diffusion and anion exclusion have been found, and natural analogue studies and in-situ experiments suggest pore connectivity in the scale of meters. Matrix diffusion, however, mostly seem to be confined to zones of higher porosity extending only a few centimeters into the rock. Surface coating material do not seem to hinder sorption or diffusion into the rock. 54 refs, 18 tabs

  19. Diagnostic accuracy of whole-brain CT perfusion in the detection of acute infratentorial infarctions

    Energy Technology Data Exchange (ETDEWEB)

    Bollwein, Christine; Sommer, Wieland H.; Thierfelder, Kolja M.; Reiser, Maximilian F. [Ludwig-Maximilians-University Hospital of Munich, Institute for Clinical Radiology, Munich (Germany); Plate, Annika; Straube, Andreas; Baumgarten, Louisa von [Ludwig-Maximilians-University Hospital of Munich, Department of Neurology, Munich (Germany); Janssen, Hendrik [South Nuremberg Hospital, Department of Neuroradiology, Nuremberg (Germany)

    2016-11-15

    Although the diagnostic performance of whole-brain computed tomographic perfusion (WB-CTP) in the detection of supratentorial infarctions is well established, its value in the detection of infratentorial strokes remains less well defined. We examined its diagnostic accuracy in the detection of infratentorial infarctions and compared it to nonenhanced computed tomography (NECT), aiming to identify factors influencing its detection rate. Out of a cohort of 1380 patients who underwent WB-CTP due to suspected stroke, we retrospectively included all patients with MRI-confirmed infratentorial strokes and compared it to control patients without infratentorial strokes. Two blinded readers evaluated NECT and four different CTP maps independently for the presence and location of infratentorial ischemic perfusion deficits. The study was designed as a retrospective case-control study and included 280 patients (cases/controls = 1/3). WB-CTP revealed a greater diagnostic sensitivity than NECT (41.4 vs. 17.1 %, P = 0.003). The specificity, however, was comparable (93.3 vs. 95.0 %). Mean transit time (MTT) and time to drain (TTD) were the most sensitive (41.4 and 40.0 %) and cerebral blood volume (CBV) the most specific (99.5 %) perfusion maps. Infarctions detected using WB-CTP were significantly larger than those not detected (15.0 vs. 2.2 ml; P = 0.0007); infarct location, however, did not influence the detection rate. The detection of infratentorial infarctions can be improved by assessing WB-CTP as part of the multimodal stroke workup. However, it remains a diagnostic challenge, especially small volume infarctions in the brainstem are likely to be missed. (orig.)

  20. Diagnostic accuracy of whole-brain CT perfusion in the detection of acute infratentorial infarctions

    International Nuclear Information System (INIS)

    Bollwein, Christine; Sommer, Wieland H.; Thierfelder, Kolja M.; Reiser, Maximilian F.; Plate, Annika; Straube, Andreas; Baumgarten, Louisa von; Janssen, Hendrik

    2016-01-01

    Although the diagnostic performance of whole-brain computed tomographic perfusion (WB-CTP) in the detection of supratentorial infarctions is well established, its value in the detection of infratentorial strokes remains less well defined. We examined its diagnostic accuracy in the detection of infratentorial infarctions and compared it to nonenhanced computed tomography (NECT), aiming to identify factors influencing its detection rate. Out of a cohort of 1380 patients who underwent WB-CTP due to suspected stroke, we retrospectively included all patients with MRI-confirmed infratentorial strokes and compared it to control patients without infratentorial strokes. Two blinded readers evaluated NECT and four different CTP maps independently for the presence and location of infratentorial ischemic perfusion deficits. The study was designed as a retrospective case-control study and included 280 patients (cases/controls = 1/3). WB-CTP revealed a greater diagnostic sensitivity than NECT (41.4 vs. 17.1 %, P = 0.003). The specificity, however, was comparable (93.3 vs. 95.0 %). Mean transit time (MTT) and time to drain (TTD) were the most sensitive (41.4 and 40.0 %) and cerebral blood volume (CBV) the most specific (99.5 %) perfusion maps. Infarctions detected using WB-CTP were significantly larger than those not detected (15.0 vs. 2.2 ml; P = 0.0007); infarct location, however, did not influence the detection rate. The detection of infratentorial infarctions can be improved by assessing WB-CTP as part of the multimodal stroke workup. However, it remains a diagnostic challenge, especially small volume infarctions in the brainstem are likely to be missed. (orig.)

  1. Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

    International Nuclear Information System (INIS)

    Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E.; Andrew, Jacquelyn I.S.; Tiwari, Akhil; Saadatmand, Heva J.; Isaacson, Steven R.; Cheng, Simon K.; Wang, Tony J.C.

    2017-01-01

    Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED 3 , the parotid doses were lower than BED 3 constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED 3 conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose constraint with BED

  2. Whole-brain Irradiation Field Design: A Comparison of Parotid Dose

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng-Chia; Wuu, Yen-Ruh; Jani, Ashish; Saraf, Anurag; Tai, Cheng-Hung; Lapa, Matthew E.; Andrew, Jacquelyn I.S.; Tiwari, Akhil; Saadatmand, Heva J. [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Isaacson, Steven R. [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Department of Neurological Surgery, Columbia University Medical Center, New York, NY 10032 (United States); Cheng, Simon K., E-mail: sc3225@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States); Wang, Tony J.C., E-mail: tjw2117@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032 (United States); Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032 (United States)

    2017-07-01

    Whole-brain radiation therapy (WBRT) plays an important role in patients with diffusely metastatic intracranial disease. Whether the extent of the radiation field design to C1 or C2 affects parotid dose and risk for developing xerostomia is unknown. The goal of this study is to examine the parotid dose based off of the inferior extent of WBRT field to either C1 or C2. Patients treated with WBRT with either 30 Gy or 37.5 Gy from 2011 to 2014 at a single institution were examined. Parotid dose constraints were compared with Radiation Therapy Oncology Group (RTOG) 0615 nasopharyngeal carcinoma for a 33-fraction treatment: mean <26 Gy, volume constraint at 20 Gy (V20) < 20 cc, and dose at 50% of the parotid volume (D50) < 30 Gy. Biologically effective dose (BED) conversions with an α/β of 3 for normal parotid were performed to compare with 10-fraction and 15-fraction treatments of WBRT. The constraints are as follows: mean < BED 32.83 Gy, V15.76 (for 10-fraction WBRT) or V17.35 (for 15-fraction WBRT) < 20 cc, and D50 < BED 39.09 Gy. Nineteen patients treated to C1 and 26 patients treated to C2 were analyzed. Comparing WBRT to C1 with WBRT to C2, the mean left, right, and both parotids' doses were lower when treated to C1. Converting mean dose to BED{sub 3}, the parotid doses were lower than BED{sub 3} constraint of 32.83 Gy: left (30.12 Gy), right (30.69 Gy), and both parotids (30.32 Gy). V20 to combined parotids was lower in patients treated to C1. When accounting for fractionation of WBRT received, the mean corrected V20 volume was less than 20 cc when treating to C1. D50 for C1 was lower than C2 for the left parotid, right parotid, and both parotids. BED{sub 3} conversion for the mean D50 of the left, right, and both parotids was less than 39.09 Gy. In conclusion, WBRT to C1 limits parotid dose, and parotid dose constraints are achievable compared with inferior border at C2. A possible mean parotid dose

  3. A Reconstruction Approach to High-Order Schemes Including Discontinuous Galerkin for Diffusion

    Science.gov (United States)

    Huynh, H. T.

    2009-01-01

    We introduce a new approach to high-order accuracy for the numerical solution of diffusion problems by solving the equations in differential form using a reconstruction technique. The approach has the advantages of simplicity and economy. It results in several new high-order methods including a simplified version of discontinuous Galerkin (DG). It also leads to new definitions of common value and common gradient quantities at each interface shared by the two adjacent cells. In addition, the new approach clarifies the relations among the various choices of new and existing common quantities. Fourier stability and accuracy analyses are carried out for the resulting schemes. Extensions to the case of quadrilateral meshes are obtained via tensor products. For the two-point boundary value problem (steady state), it is shown that these schemes, which include most popular DG methods, yield exact common interface quantities as well as exact cell average solutions for nearly all cases.

  4. Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

    Science.gov (United States)

    Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

    2018-01-22

    Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. Concussion classification via deep learning using whole-brain white matter fiber strains

    Science.gov (United States)

    Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang

    2018-01-01

    Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828–0.862 vs. 0.690–0.776, and .632+ error of 0.148–0.176 vs. 0.207–0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury. PMID:29795640

  6. Incidence of Leukoencephalopathy After Whole-Brain Radiation Therapy for Brain Metastases

    International Nuclear Information System (INIS)

    Ebi, Junko; Sato, Hisashi; Nakajima, Masaru; Shishido, Fumio

    2013-01-01

    Purpose: To evaluate the incidence of leukoencephalopathy after whole-brain radiation therapy (WBRT) in patients with brain metastases. Methods and Materials: We retrospectively reviewed 111 patients who underwent WBRT for brain metastases from April 2001 through March 2008 and had evaluable computed tomography (CT) and/or magnetic resonance imaging (MRI) at least 1 month after completion of WBRT. We evaluated the leukoencephalopathy according to the Common Terminology Criteria for Adverse Events, version 3.0. The patients who had brain tumor recurrence after WBRT were censored at the last follow-up CT or MRI without recurrence. To evaluate the risk factors for leukoencephalopathy, bivariate analysis was performed using a logistic regression analysis adjusted for follow-up time. Factors included in the analysis were age, gender, dose fractionation, 5-fluorouracil, methotrexate, cisplatin, and other chemotherapeutic agents. Results: The median age of the 111 patients was 60.0 years (range, 23-89 years). The median follow-up was 3.8 months (range, 1.0-38.1 months). Leukoencephalopathy developed in 23 of the 111 patients. Grades 1, 2, and 3 were observed in 8, 7, and 8 patients, respectively. The incidence was 34.4% (11 of 32), 42.9% (6 of 14), 66.7% (2 of 3), and 100% (2 of 2) of the patients who were followed up for ≥6, ≥12, ≥24, and ≥36 months, respectively. In the bivariate analysis, older age (≥65 years) was significantly correlated with higher risk of leukoencephalopathy (odds ratio 3.31; 95% confidence interval 1.15-9.50; P=.03). Conclusions: The incidence of leukoencephalopathy after WBRT was 34.4% with ≥6 months follow-up, and increased with longer follow-up. Older age was a significant risk factor. The schedule of WBRT for patients with brain metastases should be carefully determined, especially for favorable patients

  7. Concussion classification via deep learning using whole-brain white matter fiber strains.

    Science.gov (United States)

    Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang; Ji, Songbai

    2018-01-01

    Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828-0.862 vs. 0.690-0.776, and .632+ error of 0.148-0.176 vs. 0.207-0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury.

  8. Aberrant whole-brain functional connectivity and intelligence structure in children with primary nocturnal enuresis.

    Directory of Open Access Journals (Sweden)

    Bing Yu

    Full Text Available AIM: To assess the potential relationship between intelligence structure abnormalities and whole-brain functional connectivity in children with primary nocturnal enuresis (PNE with resting-state functional magnetic resonance imaging (fMRI to provide insights into the association between these two seemingly unrelated conditions. METHODS: Intelligence testing and fMRI data were obtained from 133 right-handed children, including 67 PNE children (M/F, 39:28; age, 10.5 ± 1.2 y and 66 age-matched healthy controls (M/F, 37:29; age, 10.1 ± 1.1 y. All intelligence tests were performed using the China-Wechsler Intelligence Scale for Children (C-WISC. Each subject's full intelligence quotient (FIQ, verbal IQ (VIQ, performance IQ (PIQ, and memory/caution (M/C factor was measured and recorded. Resting state fMRI scans were performed on a 3.0-T MR scanner and post-processed using REST software. Comparisons of z-score correlation coefficients between distinct cerebral regions were used to identify altered functional connectivity in PNE children. RESULTS: The PNE group had normal FIQ, VIQ, and PIQ values, indicating no significant variation from the control group. However, the M/C factor was significantly lower in the PNE group. Compared to the control group, PNE children exhibited overall lower levels of functional connectivity that were most apparent in the cerebello-thalamo-frontal pathway. The M/C factor significantly correlated with z-scores representing connectivity between Cerebellum_Crus1_L and Frontal_Mid_R. CONCLUSION: PNE children exhibit intelligence structure imbalance and attention deficits. Our findings suggest that cerebello-thalamo-frontal circuit abnormalities are likely to be involved in the onset and progression of attention impairment in PNE children.

  9. Whole-brain in-vivo measurements of the axonal g-ratio in a group of 37 healthy volunteers

    Directory of Open Access Journals (Sweden)

    Siawoosh eMohammadi

    2015-11-01

    Full Text Available The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain’s prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration.

  10. Electric fields, weighting fields, signals and charge diffusion in detectors including resistive materials

    CERN Document Server

    Riegler, Werner

    2016-11-07

    In this report we discuss static and time dependent electric fields in detector geometries with an arbitrary number of parallel layers of a given permittivity and weak conductivity. We derive the Green's functions i.e. the field of a point charge, as well as the weighting fields for readout pads and readout strips in these geometries. The effect of 'bulk' resistivity on electric fields and signals is investigated. The spreading of charge on thin resistive layers is also discussed in detail, and the conditions for allowing the effect to be described by the diffusion equation is discussed. We apply the results to derive fields and induced signals in Resistive Plate Chambers, Micromega detectors including resistive layers for charge spreading and discharge protection as well as detectors using resistive charge division readout like the MicroCAT detector. We also discuss in detail how resistive layers affect signal shapes and increase crosstalk between readout electrodes.

  11. Electric fields, weighting fields, signals and charge diffusion in detectors including resistive materials

    International Nuclear Information System (INIS)

    Riegler, W.

    2016-01-01

    In this report we discuss static and time dependent electric fields in detector geometries with an arbitrary number of parallel layers of a given permittivity and weak conductivity. We derive the Green's functions i.e. the field of a point charge, as well as the weighting fields for readout pads and readout strips in these geometries. The effect of 'bulk' resistivity on electric fields and signals is investigated. The spreading of charge on thin resistive layers is also discussed in detail, and the conditions for allowing the effect to be described by the diffusion equation is discussed. We apply the results to derive fields and induced signals in Resistive Plate Chambers, MICROMEGAS detectors including resistive layers for charge spreading and discharge protection as well as detectors using resistive charge division readout like the MicroCAT detector. We also discuss in detail how resistive layers affect signal shapes and increase crosstalk between readout electrodes.

  12. Simultaneous Whole-Brain Segmentation and White Matter Lesion Detection Using Contrast-Adaptive Probabilistic Models

    DEFF Research Database (Denmark)

    Puonti, Oula; Van Leemput, Koen

    2016-01-01

    In this paper we propose a new generative model for simultaneous brain parcellation and white matter lesion segmentation from multi-contrast magnetic resonance images. The method combines an existing whole-brain segmentation technique with a novel spatial lesion model based on a convolutional...... restricted Boltzmann machine. Unlike current state-of-the-art lesion detection techniques based on discriminative modeling, the proposed method is not tuned to one specific scanner or imaging protocol, and simultaneously segments dozens of neuroanatomical structures. Experiments on a public benchmark dataset...... in multiple sclerosis indicate that the method’s lesion segmentation accuracy compares well to that of the current state-of-the-art in the field, while additionally providing robust whole-brain segmentations....

  13. Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

    International Nuclear Information System (INIS)

    Chen Yingzhu; Tian Ye; Bao Shiyao; Bao Huan; Zhan Zhilin

    2007-01-01

    Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

  14. Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yingzhu, Chen; Ye, Tian; Shiyao, Bao; Huan, Bao; Zhilin, Zhan [The Second Affiliated Hospital of Suzhou Univ., Suzhou (China)

    2007-08-15

    Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

  15. Gamma knife radiosurgery for ten or more brain metastases. Analysis of the whole brain irradiation doses

    International Nuclear Information System (INIS)

    Nakaya, Kotaro; Hori, Tomokatsu; Izawa, Masahiro; Yamamoto, Masaaki

    2002-01-01

    Gamma knife (GK) radiosurgery has recently been recognized as the most powerful treatment modality in managing patients with brain metastasis, be they radioresistant or not, solitary or multiple. Very recently, this treatment has been employed in patients with numerous brain metastases, even those with 10 or more lesions. However, cumulative irradiation doses to the whole brain, with such treatment, remain unknown. Since the Gamma Plan ver. 5.10 (ver. 5.30 is presently available, Leksell Gamma Plan) became available in November, 1998, 105 GK procedures have been performed at our two facilities, Tokyo Women's Medical University and Katsuta Hospital Mito Gamma House. The median lesion number was 17, ranging 10-43, and the median cumulative volume of all tumors was 8.72 cm 3 , ranging 0.41-81.41 cm 3 . The selected doses at the lesion periphery ranged 12-25 Gy, the median being 20 Gy. Based on these treatment protocols, the cumulative irradiation dose was computed. The median cumulative irradiation dose to the whole brain was 4.83, ranging 2.16-8.51 Gy: the median integrated dose to the whole brain was 6.2 J, ranging 2.16-11.9 J. The median brain volumes receiving ≥2, ≥5, ≥10, ≥15 and ≥20 Gy were 1105 (range: 410-1501), 309 (46-1247), 64 (13-282), 24 (2-77), and 8 (0-40) cm 3 , respectively. The cumulative whole brain irradiation doses for patients with numerous radiosurgical targets were considered not to exceed the threshold level of normal brain necrosis. (author)

  16. Graph theoretical analysis reveals disrupted topological properties of whole brain functional networks in temporal lobe epilepsy.

    Science.gov (United States)

    Wang, Junjing; Qiu, Shijun; Xu, Yong; Liu, Zhenyin; Wen, Xue; Hu, Xiangshu; Zhang, Ruibin; Li, Meng; Wang, Wensheng; Huang, Ruiwang

    2014-09-01

    Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy. Previous studies have indicated that the TLE-related impairments existed in extensive local functional networks. However, little is known about the alterations in the topological properties of whole brain functional networks. In this study, we acquired resting-state BOLD-fMRI (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their whole brain functional networks, compared the differences in topological parameters between the TLE patients and the controls, and analyzed the correlation between the altered topological properties and the epilepsy duration. The TLE patients showed significant increases in clustering coefficient and characteristic path length, but significant decrease in global efficiency compared to the controls. We also found altered nodal parameters in several regions in the TLE patients, such as the bilateral angular gyri, left middle temporal gyrus, right hippocampus, triangular part of left inferior frontal gyrus, left inferior parietal but supramarginal and angular gyri, and left parahippocampus gyrus. Further correlation analysis showed that the local efficiency of the TLE patients correlated positively with the epilepsy duration. Our results indicated the disrupted topological properties of whole brain functional networks in TLE patients. Our findings indicated the TLE-related impairments in the whole brain functional networks, which may help us to understand the clinical symptoms of TLE patients and offer a clue for the diagnosis and treatment of the TLE patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Developmental venous anomalies: appearance on whole-brain CT digital subtraction angiography and CT perfusion

    International Nuclear Information System (INIS)

    Hanson, Eric H.; Roach, Cayce J.; Ringdahl, Erik N.; Wynn, Brad L.; DeChancie, Sean M.; Mann, Nathan D.; Diamond, Alan S.; Orrison, William W.

    2011-01-01

    Developmental venous anomalies (DVA) consist of dilated intramedullary veins that converge into a large collecting vein. The appearance of these anomalies was evaluated on whole-brain computed tomography (CT) digital subtraction angiography (DSA) and CT perfusion (CTP) studies. CT data sets of ten anonymized patients were retrospectively analyzed. Five patients had evidence of DVA and five age- and sex-matched controls were without known neurovascular abnormalities. CT angiograms, CT arterial-venous views, 4-D CT DSA and CTP maps were acquired on a dynamic volume imaging protocol on a 320-detector row CT scanner. Whole-brain CTP parameters were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and delay. DSA was utilized to visualize DVA anatomy. Radiation dose was recorded from the scanner console. Increased CTP values were present in the DVA relative to the unaffected contralateral hemisphere of 48%, 32%, and 26%; and for the control group with matched hemispheric comparisons of 2%, -10%, and 9% for CBF, CBV, and MTT, respectively. Average effective radiation dose was 4.4 mSv. Whole-brain DSA and CTP imaging can demonstrate a characteristic appearance of altered DVA hemodynamic parameters and capture the anomalies in superior cortices of the cerebrum and the cerebellum. Future research may identify the rare subsets of patients at increased risk of adverse outcomes secondary to the altered hemodynamics to facilitate tailored imaging surveillance and application of appropriate preventive therapeutic measures. (orig.)

  18. Brain-computer interfaces increase whole-brain signal to noise.

    Science.gov (United States)

    Papageorgiou, T Dorina; Lisinski, Jonathan M; McHenry, Monica A; White, Jason P; LaConte, Stephen M

    2013-08-13

    Brain-computer interfaces (BCIs) can convert mental states into signals to drive real-world devices, but it is not known if a given covert task is the same when performed with and without BCI-based control. Using a BCI likely involves additional cognitive processes, such as multitasking, attention, and conflict monitoring. In addition, it is challenging to measure the quality of covert task performance. We used whole-brain classifier-based real-time functional MRI to address these issues, because the method provides both classifier-based maps to examine the neural requirements of BCI and classification accuracy to quantify the quality of task performance. Subjects performed a covert counting task at fast and slow rates to control a visual interface. Compared with the same task when viewing but not controlling the interface, we observed that being in control of a BCI improved task classification of fast and slow counting states. Additional BCI control increased subjects' whole-brain signal-to-noise ratio compared with the absence of control. The neural pattern for control consisted of a positive network comprised of dorsal parietal and frontal regions and the anterior insula of the right hemisphere as well as an expansive negative network of regions. These findings suggest that real-time functional MRI can serve as a platform for exploring information processing and frontoparietal and insula network-based regulation of whole-brain task signal-to-noise ratio.

  19. Developmental venous anomalies: appearance on whole-brain CT digital subtraction angiography and CT perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Eric H. [Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); University of Nevada Las Vegas, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Box 453037, Las Vegas, NV (United States); Amigenics, Inc, Las Vegas, NV (United States); Roach, Cayce J. [Advanced Medical Imaging and Genetics (Amigenics), Las Vegas, NV (United States); University of Nevada Las Vegas, School of Life Sciences, Las Vegas, NV (United States); Ringdahl, Erik N. [University of Nevada Las Vegas, Department of Psychology, Las Vegas, NV (United States); Wynn, Brad L. [Family Medicine Spokane, Spokane, WA (United States); DeChancie, Sean M.; Mann, Nathan D. [Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); Diamond, Alan S. [CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); Orrison, William W. [Touro University Nevada College of Osteopathic Medicine, Henderson, NV (United States); University of Nevada Las Vegas, Department of Health Physics and Diagnostic Sciences, 4505 Maryland Parkway, Box 453037, Las Vegas, NV (United States); CHW Nevada Imaging Company, Nevada Imaging Centers, Spring Valley, Las Vegas, NV (United States); University of Nevada School of Medicine, Department of Medical Education, Reno, NV (United States)

    2011-05-15

    Developmental venous anomalies (DVA) consist of dilated intramedullary veins that converge into a large collecting vein. The appearance of these anomalies was evaluated on whole-brain computed tomography (CT) digital subtraction angiography (DSA) and CT perfusion (CTP) studies. CT data sets of ten anonymized patients were retrospectively analyzed. Five patients had evidence of DVA and five age- and sex-matched controls were without known neurovascular abnormalities. CT angiograms, CT arterial-venous views, 4-D CT DSA and CTP maps were acquired on a dynamic volume imaging protocol on a 320-detector row CT scanner. Whole-brain CTP parameters were evaluated for cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT), and delay. DSA was utilized to visualize DVA anatomy. Radiation dose was recorded from the scanner console. Increased CTP values were present in the DVA relative to the unaffected contralateral hemisphere of 48%, 32%, and 26%; and for the control group with matched hemispheric comparisons of 2%, -10%, and 9% for CBF, CBV, and MTT, respectively. Average effective radiation dose was 4.4 mSv. Whole-brain DSA and CTP imaging can demonstrate a characteristic appearance of altered DVA hemodynamic parameters and capture the anomalies in superior cortices of the cerebrum and the cerebellum. Future research may identify the rare subsets of patients at increased risk of adverse outcomes secondary to the altered hemodynamics to facilitate tailored imaging surveillance and application of appropriate preventive therapeutic measures. (orig.)

  20. Whole brain diffeomorphic metric mapping via integration of sulcal and gyral curves, cortical surfaces, and images

    Science.gov (United States)

    Du, Jia; Younes, Laurent; Qiu, Anqi

    2011-01-01

    This paper introduces a novel large deformation diffeomorphic metric mapping algorithm for whole brain registration where sulcal and gyral curves, cortical surfaces, and intensity images are simultaneously carried from one subject to another through a flow of diffeomorphisms. To the best of our knowledge, this is the first time that the diffeomorphic metric from one brain to another is derived in a shape space of intensity images and point sets (such as curves and surfaces) in a unified manner. We describe the Euler–Lagrange equation associated with this algorithm with respect to momentum, a linear transformation of the velocity vector field of the diffeomorphic flow. The numerical implementation for solving this variational problem, which involves large-scale kernel convolution in an irregular grid, is made feasible by introducing a class of computationally friendly kernels. We apply this algorithm to align magnetic resonance brain data. Our whole brain mapping results show that our algorithm outperforms the image-based LDDMM algorithm in terms of the mapping accuracy of gyral/sulcal curves, sulcal regions, and cortical and subcortical segmentation. Moreover, our algorithm provides better whole brain alignment than combined volumetric and surface registration (Postelnicu et al., 2009) and hierarchical attribute matching mechanism for elastic registration (HAMMER) (Shen and Davatzikos, 2002) in terms of cortical and subcortical volume segmentation. PMID:21281722

  1. Altered integrity of the right arcuate fasciculus as a trait marker of schizophrenia: a sibling study using tractography-based analysis of the whole brain.

    Science.gov (United States)

    Wu, Chen-Hao; Hwang, Tzung-Jeng; Chen, Yu-Jen; Hsu, Yun-Chin; Lo, Yu-Chun; Liu, Chih-Min; Hwu, Hai-Gwo; Liu, Chen-Chung; Hsieh, Ming H; Chien, Yi Ling; Chen, Chung-Ming; Tseng, Wen-Yih Isaac

    2015-03-01

    Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association. © 2014 Wiley Periodicals, Inc.

  2. Characterization of cortical neuronal and glial alterations during culture of organotypic whole brain slices from neonatal and mature mice.

    Science.gov (United States)

    Staal, Jerome A; Alexander, Samuel R; Liu, Yao; Dickson, Tracey D; Vickers, James C

    2011-01-01

    Organotypic brain slice culturing techniques are extensively used in a wide range of experimental procedures and are particularly useful in providing mechanistic insights into neurological disorders or injury. The cellular and morphological alterations associated with hippocampal brain slice cultures has been well established, however, the neuronal response of mouse cortical neurons to culture is not well documented. In the current study, we compared the cell viability, as well as phenotypic and protein expression changes in cortical neurons, in whole brain slice cultures from mouse neonates (P4-6), adolescent animals (P25-28) and mature adults (P50+). Cultures were prepared using the membrane interface method. Propidium iodide labeling of nuclei (due to compromised cell membrane) and AlamarBlue™ (cell respiration) analysis demonstrated that neonatal tissue was significantly less vulnerable to long-term culture in comparison to the more mature brain tissues. Cultures from P6 animals showed a significant increase in the expression of synaptic markers and a decrease in growth-associated proteins over the entire culture period. However, morphological analysis of organotypic brain slices cultured from neonatal tissue demonstrated that there were substantial changes to neuronal and glial organization within the neocortex, with a distinct loss of cytoarchitectural stratification and increased GFAP expression (pglial limitans and, after 14 DIV, displayed substantial cellular protrusions from slice edges, including cells that expressed both glial and neuronal markers. In summary, we present a substantial evaluation of the viability and morphological changes that occur in the neocortex of whole brain tissue cultures, from different ages, over an extended period of culture.

  3. SU-D-BRD-06: Automated Population-Based Planning for Whole Brain Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schreibmann, E; Fox, T; Crocker, I; Shu, H [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2014-06-01

    Purpose: Treatment planning for whole brain radiation treatment is technically a simple process but in practice it takes valuable clinical time of repetitive and tedious tasks. This report presents a method that automatically segments the relevant target and normal tissues and creates a treatment plan in only a few minutes after patient simulation. Methods: Segmentation is performed automatically through morphological operations on the soft tissue. The treatment plan is generated by searching a database of previous cases for patients with similar anatomy. In this search, each database case is ranked in terms of similarity using a customized metric designed for sensitivity by including only geometrical changes that affect the dose distribution. The database case with the best match is automatically modified to replace relevant patient info and isocenter position while maintaining original beam and MLC settings. Results: Fifteen patients were used to validate the method. In each of these cases the anatomy was accurately segmented to mean Dice coefficients of 0.970 ± 0.008 for the brain, 0.846 ± 0.009 for the eyes and 0.672 ± 0.111 for the lens as compared to clinical segmentations. Each case was then subsequently matched against a database of 70 validated treatment plans and the best matching plan (termed auto-planned), was compared retrospectively with the clinical plans in terms of brain coverage and maximum doses to critical structures. Maximum doses were reduced by a maximum of 20.809 Gy for the left eye (mean 3.533), by 13.352 (1.311) for the right eye, and by 27.471 (4.856), 25.218 (6.315) for the left and right lens. Time from simulation to auto-plan was 3-4 minutes. Conclusion: Automated database- based matching is an alternative to classical treatment planning that improves quality while providing a cost—effective solution to planning through modifying previous validated plans to match a current patient's anatomy.

  4. Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-12-01

    . Patients with extensive diffuse metastases (≥10 BM were associated with higher odds of PHM. Keywords: breast cancer, hippocampal metastases, brain metastasis, whole-brain radiation therapy

  5. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  6. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  7. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Science.gov (United States)

    Rzucidlo, Justyna K; Roseman, Paige L; Laurienti, Paul J; Dagenbach, Dale

    2013-01-01

    Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  8. SU-E-J-171: Surface Imaging Based Intrafraction Motion Assessments for Whole Brain Radiotherapy

    International Nuclear Information System (INIS)

    Wiant, D; Vanderstraeten, C; Maurer, J; Pursley, J; Terrell, J; Sintay, B

    2014-01-01

    Purpose: To quantify and characterize intrafraction motion for whole brain radiotherapy treatments in open face masks using 3D surface imaging. Methods: Fifteen whole brain patients were monitored with 3D surface imaging over a total of 202 monitoring sessions. Mean translations and rotations were calculated over each minute, each session, and over all sessions combined. The percentage of each session that the root mean square (RMS) of the linear translations were outside of 2 mm, 3 mm, 4 mm, and 5 mm were determined for each patient. Correlations between mean translations per minute and time and between standard deviation per minute and time were evaluated using Pearson's r value. Results: The mean RMS translation averaged over all patients was 1.45 mm +/− 1.52 mm. The patients spent an average of 18%, 10%, 6%, and 3% of the monitoring time outside of 2 mm, 3 mm, 4 mm, and 5 mm RMS tolerances, respectively. The RMS values averaged over all patients were 1.31 mm +/− 0.98 mm, 1.52 +/- 1.04, and 1.30 mm +/− 0.71 mm over the 1th, 5th, and 10th minutes of monitoring, respectively. Neither, the RMS values (p = 0.15) or the standard deviations of the RMS values (p = 0.16) showed significant correlations with time. Conclusion: The patients were positioned within 2 mm of isocenter, which was the initial set-up tolerance, for the majority of their treatments. The average position changed by < 0.3 mm over 10 minutes of monitoring. Short term movements, reflected by the standard deviations, where on the order of 1 mm. This immobilization system provides adequate immobilization over a course of treatment for whole brain radiotherapy. This system may also be suitable for head and neck or stereotactic radiosurgery treatments as well

  9. Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

    International Nuclear Information System (INIS)

    Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric T.; Uhlmann, Erik J.; Sengupta, Soma; Kasper, Ekkehard M.

    2015-01-01

    Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V 24 (9 cc vs. 44 cc, p < 0.0000) and V 30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

  10. Disruption of functional networks in dyslexia: A whole-brain, data-driven analysis of connectivity

    Science.gov (United States)

    Finn, Emily S.; Shen, Xilin; Holahan, John M.; Scheinost, Dustin; Lacadie, Cheryl; Papademetris, Xenophon; Shaywitz, Sally E.; Shaywitz, Bennett A.; Constable, R. Todd

    2013-01-01

    Background Functional connectivity analyses of fMRI data are a powerful tool for characterizing brain networks and how they are disrupted in neural disorders. However, many such analyses examine only one or a small number of a priori seed regions. Studies that consider the whole brain frequently rely on anatomic atlases to define network nodes, which may result in mixing distinct activation timecourses within a single node. Here, we improve upon previous methods by using a data-driven brain parcellation to compare connectivity profiles of dyslexic (DYS) versus non-impaired (NI) readers in the first whole-brain functional connectivity analysis of dyslexia. Methods Whole-brain connectivity was assessed in children (n = 75; 43 NI, 32 DYS) and adult (n = 104; 64 NI, 40 DYS) readers. Results Compared to NI readers, DYS readers showed divergent connectivity within the visual pathway and between visual association areas and prefrontal attention areas; increased right-hemisphere connectivity; reduced connectivity in the visual word-form area (part of the left fusiform gyrus specialized for printed words); and persistent connectivity to anterior language regions around the inferior frontal gyrus. Conclusions Together, findings suggest that NI readers are better able to integrate visual information and modulate their attention to visual stimuli, allowing them to recognize words based on their visual properties, while DYS readers recruit altered reading circuits and rely on laborious phonology-based “sounding out” strategies into adulthood. These results deepen our understanding of the neural basis of dyslexia and highlight the importance of synchrony between diverse brain regions for successful reading. PMID:24124929

  11. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Directory of Open Access Journals (Sweden)

    Justyna K Rzucidlo

    Full Text Available BACKGROUND: Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. METHODOLOGY/PRINCIPAL FINDINGS: fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. CONCLUSIONS/SIGNIFICANCE: These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  12. Impact of drug permeability of blood-brain barrier after whole brain conventional fractionation irradiation

    International Nuclear Information System (INIS)

    Zhang Longzhen; Cao Yuandong; Chen Yong; Yu Changzhou; Zhuang Ming

    2006-01-01

    Objective: To explore the effect of drug permeability in rat blood-brain barrier(BBB) after different doses of whole brain conventional fractionation irradiation in rats and provide the experimental basis for the optimum time of clinical chemotherapy. Methods: According to different irradiation doses, 100 adult Sprague-Dowley rats were divided randomly into 5 groups: the normal control group(0 Gy); 10 Gy; 20 Gy; 30 Gy; and 40 Gy group. All rats were exposed to conventional fractionation(2 Gy/d, 5 d/w) with 60 Co γ-ray. MTX(25 mg/kg) was injected through the tail mainline 16 hours after whole brain irradiation. Cerebrospinal fluid(CSF) and blood were collected 2 hours later. Those samples were used to assay MTX concentration using RP-HPLC. Results: MTX mean concentrations in CSF was 0.07, 0.08, 0.12, 0.24, 0.23 mg/L in the control, 10 Gy, 20 Gy, 30 Gy, 40 Gy groups, respectively. All the data was analyzed with rank test of transform. MTX concentration of CSF was significantly different except the control and 10 Gy, 30 Gy and 40 Gy group. MTX concentration of blood was not significantly different in all groups (P>0.05). Conclusions: Irradiation can directly damage the function of BBB. BBB would be opened gradually following the increase of irradiation dose. It could be considered as the optimum time of chemotherapy when the whole brain irradiation ranges from 20 Gy to 30 Gy. (authors)

  13. Whole brain and brain regional coexpression network interactions associated with predisposition to alcohol consumption.

    Directory of Open Access Journals (Sweden)

    Lauren A Vanderlinden

    Full Text Available To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA. Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL with a genomic region that regulates alcohol consumption (bQTL. To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we compared candidate coexpression modules from whole brain gene expression data (gathered with Affymetrix 430 v2 arrays in the Colorado laboratories and from gene expression data from 6 brain regions (nucleus accumbens (NA; prefrontal cortex (PFC; ventral tegmental area (VTA; striatum (ST; hippocampus (HP; cerebellum (CB available from GeneNetwork. The candidate modules were used to construct candidate eigengene networks across brain regions, resulting in three "meta-modules", composed of candidate modules from two or more brain regions (NA, PFC, ST, VTA and whole brain. To mitigate the potential influence of chromosomal location of transcripts and cis-eQTLs in linkage disequilibrium, we calculated a semi-partial correlation of the transcripts in the meta-modules with alcohol consumption conditional on the transcripts' cis-eQTLs. The function of transcripts that retained the correlation with the phenotype after correction for the strong genetic influence, implicates processes of protein metabolism in the ER and Golgi as influencing susceptibility to variation in alcohol consumption. Integration of these data with human GWAS provides further information on the function of polymorphisms associated with alcohol-related traits.

  14. Characterization of [(3)H]harmane binding to rat whole brain membranes.

    Science.gov (United States)

    Anderson, N J; Robinson, E S J; Husbands, S M; Delagrange, P; Nutt, D J; Hudson, A L

    2003-12-01

    This study investigates the binding of [(3)H]harmane to rat whole brain homogenates. Saturation studies revealed [(3)H]harmane labels a single, saturable, high-capacity population with high affinity. All the test compounds displaced [(3)H]harmane completely and in an apparently monophasic manner. The displacement profile of the test ligands indicated labeling of MAO-A. Given the high level of MAO-A binding, it is unlikely that a low-capacity I(2) site would be distinguishable from the total [(3)H]harmane population.

  15. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

    Science.gov (United States)

    Patil, Chirag G; Pricola, Katie; Sarmiento, J Manuel; Garg, Sachin K; Bryant, Andrew; Black, Keith L

    2017-09-25

    Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in

  16. A LES-CMC formulation for premixed flames including differential diffusion

    Science.gov (United States)

    Farrace, Daniele; Chung, Kyoungseoun; Bolla, Michele; Wright, Yuri M.; Boulouchos, Konstantinos; Mastorakos, Epaminondas

    2018-05-01

    A finite volume large eddy simulation-conditional moment closure (LES-CMC) numerical framework for premixed combustion developed in a previous studyhas been extended to account for differential diffusion. The non-unity Lewis number CMC transport equation has an additional convective term in sample space proportional to the conditional diffusion of the progress variable, that in turn accounts for diffusion normal to the flame front and curvature-induced effects. Planar laminar simulations are first performed using a spatially homogeneous non-unity Lewis number CMC formulation and validated against physical-space fully resolved reference solutions. The same CMC formulation is subsequently used to numerically investigate the effects of curvature for laminar flames having different effective Lewis numbers: a lean methane-air flame with Leeff = 0.99 and a lean hydrogen-air flame with Leeff = 0.33. Results suggest that curvature does not affect the conditional heat release if the effective Lewis number tends to unity, so that curvature-induced transport may be neglected. Finally, the effect of turbulence on the flame structure is qualitatively analysed using LES-CMC simulations with and without differential diffusion for a turbulent premixed bluff body methane-air flame exhibiting local extinction behaviour. Overall, both the unity and the non-unity computations predict the characteristic M-shaped flame observed experimentally, although some minor differences are identified. The findings suggest that for the high Karlovitz number (from 1 to 10) flame considered, turbulent mixing within the flame weakens the differential transport contribution by reducing the conditional scalar dissipation rate and accordingly the conditional diffusion of the progress variable.

  17. Magnetic resonance imaging of epidermoid, including diffusion weighted images and an atypical case

    International Nuclear Information System (INIS)

    Takahashi, Shoki; Higano, Shuichi; Kurihara, Noriko

    1994-01-01

    In order to study the role of magnetic resonance imaging (MRI) in diagnosing intracranial epidermoid, we evaluated the MRI findings on five cases with such tumor, all of which were surgically verified. In addition to standard spin-echo (SE) images obtained in all cases, diffusion-weighted images were acquired in two patients. In four patients, the tumor revealed to be almost isointense relative to cerebrospinal fluid (CSF) on both T 1 -and T 2 -weighted images, while it tended to show slightly hyperintense to CSF on proton-density-weighted images; thus, based on the signal intensity on standard SE images the distinction between epidermoid and arachnoid cyst may be difficult. Furthermore, the presence of the tumor which has a tendency to grow in and along the subarachnoid space causing relatively minimal mass effect may be overlooked. Diffusion-weighted images were shown to have advantages in such cases by demonstrating the tumor unequivocally as a mass of high signal, and differentiating it from arachnoid cysts. In the remaining patient, its appearance was atypical, showing bright signal on both T 1 -and T 2 -weighted images. In conclusion free of bone artifacts, multiplanar MRI with additional diffusion-weighted images provides a clear demonstration of epidermoid, and its differentiation from arachnoid cyst, thus obviating the need for CT cisternography. (author)

  18. Discriminative analysis of Parkinson's disease based on whole-brain functional connectivity.

    Directory of Open Access Journals (Sweden)

    Yongbin Chen

    Full Text Available Recently, there has been an increasing emphasis on applications of pattern recognition and neuroimaging techniques in the effective and accurate diagnosis of psychiatric or neurological disorders. In the present study, we investigated the whole-brain resting-state functional connectivity patterns of Parkinson's disease (PD, which are expected to provide additional information for the clinical diagnosis and treatment of this disease. First, we computed the functional connectivity between each pair of 116 regions of interest derived from a prior atlas. The most discriminative features based on Kendall tau correlation coefficient were then selected. A support vector machine classifier was employed to classify 21 PD patients with 26 demographically matched healthy controls. This method achieved a classification accuracy of 93.62% using leave-one-out cross-validation, with a sensitivity of 90.47% and a specificity of 96.15%. The majority of the most discriminative functional connections were located within or across the default mode, cingulo-opercular and frontal-parietal networks and the cerebellum. These disease-related resting-state network alterations might play important roles in the pathophysiology of this disease. Our results suggest that analyses of whole-brain resting-state functional connectivity patterns have the potential to improve the clinical diagnosis and treatment evaluation of PD.

  19. Pencilbeam irradiation technique for whole brain radiotherapy: technical and biological challenges in a small animal model.

    Science.gov (United States)

    Schültke, Elisabeth; Trippel, Michael; Bräuer-Krisch, Elke; Renier, Michel; Bartzsch, Stefan; Requardt, Herwig; Döbrössy, Máté D; Nikkhah, Guido

    2013-01-01

    We have conducted the first in-vivo experiments in pencilbeam irradiation, a new synchrotron radiation technique based on the principle of microbeam irradiation, a concept of spatially fractionated high-dose irradiation. In an animal model of adult C57 BL/6J mice we have determined technical and physiological limitations with the present technical setup of the technique. Fifty-eight animals were distributed in eleven experimental groups, ten groups receiving whole brain radiotherapy with arrays of 50 µm wide beams. We have tested peak doses ranging between 172 Gy and 2,298 Gy at 3 mm depth. Animals in five groups received whole brain radiotherapy with a center-to-center (ctc) distance of 200 µm and a peak-to-valley ratio (PVDR) of ∼ 100, in the other five groups the ctc was 400 µm (PVDR ∼ 400). Motor and memory abilities were assessed during a six months observation period following irradiation. The lower dose limit, determined by the technical equipment, was at 172 Gy. The LD50 was about 1,164 Gy for a ctc of 200 µm and higher than 2,298 Gy for a ctc of 400 µm. Age-dependent loss in motor and memory performance was seen in all groups. Better overall performance (close to that of healthy controls) was seen in the groups irradiated with a ctc of 400 µm.

  20. Accelerated whole-brain multi-parameter mapping using blind compressed sensing.

    Science.gov (United States)

    Bhave, Sampada; Lingala, Sajan Goud; Johnson, Casey P; Magnotta, Vincent A; Jacob, Mathews

    2016-03-01

    To introduce a blind compressed sensing (BCS) framework to accelerate multi-parameter MR mapping, and demonstrate its feasibility in high-resolution, whole-brain T1ρ and T2 mapping. BCS models the evolution of magnetization at every pixel as a sparse linear combination of bases in a dictionary. Unlike compressed sensing, the dictionary and the sparse coefficients are jointly estimated from undersampled data. Large number of non-orthogonal bases in BCS accounts for more complex signals than low rank representations. The low degree of freedom of BCS, attributed to sparse coefficients, translates to fewer artifacts at high acceleration factors (R). From 2D retrospective undersampling experiments, the mean square errors in T1ρ and T2 maps were observed to be within 0.1% up to R = 10. BCS was observed to be more robust to patient-specific motion as compared to other compressed sensing schemes and resulted in minimal degradation of parameter maps in the presence of motion. Our results suggested that BCS can provide an acceleration factor of 8 in prospective 3D imaging with reasonable reconstructions. BCS considerably reduces scan time for multiparameter mapping of the whole brain with minimal artifacts, and is more robust to motion-induced signal changes compared to current compressed sensing and principal component analysis-based techniques. © 2015 Wiley Periodicals, Inc.

  1. Applicability of the 3D-VIBE sequence to whole brain imaging

    International Nuclear Information System (INIS)

    Makabe, Takeshi; Nakamura, Manami; Moriyama, Ryo

    2009-01-01

    The volumetric interpolated breath-hold examination (VIBE) method has been developed imaging also holds its breath in an abdomen, and to do three-dimensional T1WI in possible time in gradient echo sequence, and applied to dynamic study mainly and planning for time reduction using an interpolation and partial fourier. We considered the condition for imaging to do whole brain as high resolution image using VIBE. Even if base matrix was maintained when an interpolation and partial fourier were used too much excessively by Phantom experiment, the resolution of multiplanar reconstruction (MPR) image fell. There was a limit of the interpolation therefore to maintain the resolution as voxel. Signal-to-noise ratio (SNR) fell by flip angle (FA) increase by the applicability to the head, and peak existed in about 15 deg in contrast-to-noise ratio (CNR) of white matter and gray matter. Therefore by it's clinical and optimizing the imaging condition of VIBE, whole brain, it was imaging possible in about 3 minutes as high resolution image. (author)

  2. Structural alterations of the DNA in cerebellar neurons after whole-brain irradiation

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Winstein, R.E.; Kaufman, K.; Ritter, P.

    1981-01-01

    Male Sprague-Dawley rats weighing 260 to 280 g were whole-brain-irradiated with x-ray doses of 433, 867, 1083, 1300, 1516, and 1713 rad. Over the next 2.25 years rats were killed at various times, and the state of the DNA in their cerebellar neurons was examined by sedimentation through alkaline sucrose gradients in reorienting zonal rotors. The data were analyzed as the percentage of the sedimenting DNA with sedimentation coefficients greater than 300 S, an arbitrarily selected category of no defined molecular significance. The general pattern at all doses consisted first of a slow return to the unirradiated DNA state that was relatively dose dependent. This was followed by an increase in the amount of DNA sedimenting >300 S; both the extent and time course of this increase appeared to be dose dependent. Finally, the DNA degraded at a relatively dose independent rate. There was little change in the neuronal DNA from unirradiated rats during this study. The data suggest that increases in the amount of fast-sedimenting DNA observed 30 to 80 weeks after low to moderate doses of whole-brain irradiation represent a type of DNA damage rather than repair and that this damage ultimately results in degradation of the neuronal DNA and death of the rat

  3. Measurement of radiation dose to the eye-lens with bilateral whole brain irradiation

    International Nuclear Information System (INIS)

    Kim, Ki Hwan; Park, Charn Il; Kang, Wee Saing; Choo, Dong Woon

    1985-01-01

    In 40 patients with metastatic brain tumor and acute lymphoblastic leukemia received whole brain irradiation, the dose delivered to the eye lens was measured using T.L.D. chips applied on the eyes as usual shield. The dose to the eye lens was expressed the relative dose to the mid brain dose. Radiotherapy was administrated using Co-60 teletherapy with bilateral whole brain irradiation. The results are as follows: 1. The dose to the right eye from its incipient field is 16.6% of tumor dose while the dose to the same eye from the opposite field is 41.2%. On left eye, 19.2% from incipient field while 39.2% from the opposite field. 2. Total received dose to right and left eyes is 28.9%, 29.8% of tumor dose respectively. 3. Comparing lens shield group with orbit shield group dose is 22.5%, 15.8% of tumor dose, respectively. 4. The dose delivered to the eye lens in ipsilateral side depends upon internal scattering, location of lead shield and penetrating dose of lead in itself. The dose in contralateral side depends upon divergency of radiation beam and patient's malposition. 5. The dose to the eye lens should be less than 10% of tumor dose with adequate shield, also not missing the chance of leptomeningeal recurrence because of overshielding.

  4. Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

    Science.gov (United States)

    Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

    2012-03-01

    Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

  5. Diffusion

    International Nuclear Information System (INIS)

    Kubaschewski, O.

    1983-01-01

    The diffusion rate values of titanium, its compounds and alloys are summarized and tabulated. The individual chemical diffusion coefficients and self-diffusion coefficients of certain isotopes are given. Experimental methods are listed which were used for the determination of diffusion coefficients. Some values have been taken over from other studies. Also given are graphs showing the temperature dependences of diffusion and changes in the diffusion coefficient with concentration changes

  6. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  7. The development and investigation of a prototype three-dimensional compensator for whole brain radiation therapy

    International Nuclear Information System (INIS)

    Keall, Paul; Arief, Isti; Shamas, Sofia; Weiss, Elisabeth; Castle, Steven

    2008-01-01

    Whole brain radiation therapy (WBRT) is the standard treatment for patients with brain metastases, and is often used in conjunction with stereotactic radiotherapy for patients with a limited number of brain metastases, as well as prophylactic cranial irradiation. The use of open fields (conventionally used for WBRT) leads to higher doses to the brain periphery if dose is prescribed to the brain center at the largest lateral radius. These dose variations potentially compromise treatment efficacy and translate to increased side effects. The goal of this research was to design and construct a 3D 'brain wedge' to compensate dose heterogeneities in WBRT. Radiation transport theory was invoked to calculate the desired shape of a wedge to achieve a uniform dose distribution at the sagittal plane for an ellipsoid irradiated medium. The calculations yielded a smooth 3D wedge design to account for the missing tissue at the peripheral areas of the brain. A wedge was machined based on the calculation results. Three ellipsoid phantoms, spanning the mean and ± two standard deviations from the mean cranial dimensions were constructed, representing 95% of the adult population. Film was placed at the sagittal plane for each of the three phantoms and irradiated with 6 MV photons, with the wedge in place. Sagittal plane isodose plots for the three phantoms demonstrated the feasibility of this wedge to create a homogeneous distribution with similar results observed for the three phantom sizes, indicating that a single wedge may be sufficient to cover 95% of the adult population. The sagittal dose is a reasonable estimate of the off-axis dose for whole brain radiation therapy. Comparing the dose with and without the wedge the average minimum dose was higher (90% versus 86%), the maximum dose was lower (107% versus 113%) and the dose variation was lower (one standard deviation 2.7% versus 4.6%). In summary, a simple and effective 3D wedge for whole brain radiotherapy has been developed

  8. Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.

    Science.gov (United States)

    Wirsich, Jonathan; Perry, Alistair; Ridley, Ben; Proix, Timothée; Golos, Mathieu; Bénar, Christian; Ranjeva, Jean-Philippe; Bartolomei, Fabrice; Breakspear, Michael; Jirsa, Viktor; Guye, Maxime

    2016-01-01

    The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

  9. Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

    Science.gov (United States)

    Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

    2016-03-01

    Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Sequential Magnetic Resonance Imaging Finding of Intramedullary Spinal Cord Abscess including Diffusion Weighted Image: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Jae Eun; Lee, Seung Young; Cha, Sang Hoon; Cho, Bum Sang; Jeon, Min Hee; Kang, Min Ho [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2011-04-15

    Intramedullary spinal cord abscess (ISCA) is a rare infection of the central nervous system. We describe the magnetic resonance imaging (MRI) findings, including the diffusion-weighted imaging (DWI) findings, of ISCA in a 78-year-old man. The initial conventional MRI of the thoracic spine demonstrated a subtle enhancing nodule accompanied by significant edema. On the follow-up MRI after seven days, the nodule appeared as a ring-enhancing nodule. The non-enhancing central portion of the nodule appeared hyperintense on DWI with a decreased apparent diffusion coefficient (ADC) value on the ADC map. We performed myelotomy and surgical drainage, and thick, yellowish pus was drained

  11. Assessment of cognitive functions after prophylactic and therapeutic whole brain irradiation using neuropsychological testing; Erfassung kognitiver Funktionen nach prophylaktischer und therapeutischer Ganzhirnbestrahlung mittels neuropsychologischer Testverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Penitzka, S.; Wannenmacher, M. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Steinvorth, S. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; MIT, Cambridge, MT (United States). Dept. of Brain and Cognitive Sciences; Sehlleier, S. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Universitaetsklinikum Wuerzburg (Germany). Abt. Strahlentherapie; Fuss, M. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Texas Univ., San Antonio, TX (United States). Health Science Center; Wenz, F. [Universitaetsklinikum Heidelberg (Germany). Abt. Klinische Radiologie; Universitaetsklinikum Mannheim (Germany). Sektion Radioonkologie

    2002-05-01

    Purpose: Aim of this study was the assessment of neuropsychological changes after whole brain irradiation. Patients and Method: 64 patients were tested before, and 29 after whole brain irradiation, including 28 patients with small cell lung cancer (SCLC) before prophylactic cranial irradiation (PCI) and 36 patients with cerebral metastases before therapeutic cranial irradiation (TCI), as well as 14 patients after PCI and 15 after TCI (Table 1). Intelligence, attention and memory were assessed applying a 90-minute test battery of standardized, neuropsychological tests (Table 3). Results: Patients with SCLC showed test results significantly below average before PCI (n=28, mean IQ=83, SD=17). Neither after PCI, nor after TCI the tested neuropsychological functions decreased significantly (Tables 4, 5). A comparison between SCLC-patients with and without cerebral metastases before whole brain irradiation showed better test-results in patients with cerebral metastases and fewer cycles of preceding chemotherapy (Table 7). Conclusion: Neuropsychological capacity in patients with SCLC was impaired even before PCI. Possible reason is the preceding chemotherapy. Whole brain irradiation did not induce a significant decline of cognitive functions in patients with PCI or TCI. A decline in a longer follow-up nevertheless seems possible. (orig.) [German] Zielsetzung: Ziel der Studie war die Erfassung moeglicher Veraenderungen der neuropsychologischen Leistungsfaehigkeit nach Ganzhirnbestrahlung. Patienten und Methode: Untersucht wurden 64 Patienten vor und 29 Patienten nach Ganzhirnbestrahlung. Es handelte sich um 28 Patienten mit kleinzelligem Bronchialkarzinom (SCLC) vor prophylaktischer Ganzhirnbestrahlung (PCI) und um 36 Patienten mit Hirnmetastasen vor therapeutischer Ganzhirnbestrahlung (TCI). Es wurden 14 Patienten nach PCI und 15 Patienten nach TCI getestet. Zur Anwendung kam eine 90-minuetige Testbatterie standardisierter, neuropsychologischer Testverfahren zur Messung

  12. Whole-brain blood flow and oxygen metabolism in the rat after halothane anesthesia

    Energy Technology Data Exchange (ETDEWEB)

    Gjedde, A; Hindfeldt, B [Cerebrovascular Research Center, Department of Neurology, The New York Hospital-Cornell Medical Center, New York, U.S.A.; Department of Neurology, University Hospital, Lund, Sweden)

    1975-01-01

    A recent modification of the Kety-Schmidt wash-out technique for /sup 133/xenon was used to measure whole-brain flow (CBF) and oxygen consumption (CMRsub(o2)) 1 to 4 hours after termination of halothane anesthesia in 15 Wistar rats. In this 3-hour experimental period, mean CBF and CMRsub(o2) were reduced to 29 and 43 percent of control values, respectively. CBF and CMRsub(o2) determined at the beginning and end of the experimental period were not significantly different from each other. Cerebral venous O/sub 2/ tension was significantly higher than in the control group, supporting recent suggestions of a primary, intrinsic effect of halothane on the homeostatic control of this variable. It is concluded that halothane is not useful for cerebral metabolic studies in the rat.

  13. Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed.

    Science.gov (United States)

    Brown, Paul D; Asher, Anthony L; Farace, Elana

    2008-04-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

  14. Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior.

    Science.gov (United States)

    Portugues, Ruben; Feierstein, Claudia E; Engert, Florian; Orger, Michael B

    2014-03-19

    Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate but ordered pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: brown.paul@mayo.edu; Asher, Anthony L [Brain and Spinal Cord Tumors Programs, Carolinas Medical Center and Presbyterian Hospital, Charlotte, NC (United States); Farace, Elana [Department of Neurosurgery, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, Hershey, PA (United States)

    2008-04-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

  16. Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

    International Nuclear Information System (INIS)

    Brown, Paul D.; Asher, Anthony L.; Farace, Elana

    2008-01-01

    Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival

  17. Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging.

    Science.gov (United States)

    Susaki, Etsuo A; Tainaka, Kazuki; Perrin, Dimitri; Yukinaga, Hiroko; Kuno, Akihiro; Ueda, Hiroki R

    2015-11-01

    Here we describe a protocol for advanced CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis). The CUBIC protocol enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples. The organ or body is cleared by immersion for 1-14 d, with the exact time required dependent on the sample type and the experimental purposes. A single imaging set can be completed in 30-60 min. Image processing and analysis can take whole-brain neural activities at single-cell resolution using Arc-dVenus transgenic (Tg) mice. CUBIC informatics calculated the Venus signal subtraction, comparing different brains at a whole-organ scale. These protocols provide a platform for organism-level systems biology by comprehensively detecting cells in a whole organ or body.

  18. TDat: An Efficient Platform for Processing Petabyte-Scale Whole-Brain Volumetric Images.

    Science.gov (United States)

    Li, Yuxin; Gong, Hui; Yang, Xiaoquan; Yuan, Jing; Jiang, Tao; Li, Xiangning; Sun, Qingtao; Zhu, Dan; Wang, Zhenyu; Luo, Qingming; Li, Anan

    2017-01-01

    Three-dimensional imaging of whole mammalian brains at single-neuron resolution has generated terabyte (TB)- and even petabyte (PB)-sized datasets. Due to their size, processing these massive image datasets can be hindered by the computer hardware and software typically found in biological laboratories. To fill this gap, we have developed an efficient platform named TDat, which adopts a novel data reformatting strategy by reading cuboid data and employing parallel computing. In data reformatting, TDat is more efficient than any other software. In data accessing, we adopted parallelization to fully explore the capability for data transmission in computers. We applied TDat in large-volume data rigid registration and neuron tracing in whole-brain data with single-neuron resolution, which has never been demonstrated in other studies. We also showed its compatibility with various computing platforms, image processing software and imaging systems.

  19. Long-term effects of whole brain radiation on intellectual function in children with medulloblastoma

    International Nuclear Information System (INIS)

    Uozumi, Akimasa; Okimura, Yoshitaka; Ohsato, Katsunobu; Yamaura, Akira; Hasegawa, Keiko

    1992-01-01

    Neuropsychological tests were administered to four children 4 to 10 years after treatment of medulloblastoma with surgery, radiation, and natural alpha-interferon. The age at the time of treatment ranged from 2 years and 4 months to 11 years. The radiation doses were 26-34 Gy to the whole brain, 48-52 Gy to the posterior fossa and 26-34 Gy to the whole spine. Uneventful follow-up periods ranged from 4 years and 8 months to 10 years and 6 months. At present they attend regular classes at local schools. The neuropsychological tests used were: Wechsler Intelligence Scale for Children-Revised (WISC-R), Frostig developmental test of visual perception and Uchida-Kraepelin psychometric test. The WISC-R showed a marked decrease of full-scale IQ in two of the four children (scores of 72 and 73). Their performance IQ scores were significantly lower than their verbal scores. This may reflect less ability to manage visual and spatial information than verbal information. The other two patients had full-scale IQ scores of 91 and 92 (within the normal range). The test of visual perception showed decreased ability in the three patients who were younger than 8 years, of age at the time of treatment but normal ability in the child who had been treated at 11 years of age. The Uchida-Kraepelin test showed reduced amounts of work accomplished and poor learning ability in all four patients. These findings suggest that intellectual function in children with medulloblastoma is affected by the failure of visual perception to develop normally because of whole brain radiation at an early age and that their problem is aggravated by secondary learning difficulties. It is necessary to provide these patients with individual learning programs based on the results of neuropsychological evaluations. (author)

  20. The expression changes of inflammatory cytokines in the hippocampus following whole-brain irradiation in rats

    International Nuclear Information System (INIS)

    Yu De; Tian Ye; Ding Weijun; Zhu Yaqun; Liu Chunfeng

    2004-01-01

    To investigate the change pattern of some inflammatory cytokines in brain tissue at the acute phase after brain irradiated. The whole brain of SD rats was irradiated by the single dose of 2, 15 or 30 Gy of 4 MeV electron beam. The enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-1 β, IL-6, and TNF-α content in hippocampus tissue of rats at 1h, 6h, 12h, 1d, 2 and 1 week post-irradiation. The mRNA of IL-1 β, IL-6, and TNF-α were detected by reverse-transcription polymerase chain reaction (RT-PCR) in the same experimental groups. It was analyzed about the influence of dosage and post-irradiation duration with the cytokines expression. Compared with both the normal control and the anesthetized with chloral hydrate but sham-irradiation groups, there were no difference about the three inflammatory cytokines expression in rats with 2 Gy irradiated. At 6h after irradiation with 15 Gy, 6 and 12h with 30 Gy groups, the content of IL-1β and TNF-α in hippocampus tissue were significantly increased, and were returned to normal level after 12 to 24h. The same change tendency of their mRNA relational level was observed in 15 and 30 Gy groups, but it happened earlier in 1h after exposure. Although the content of IL-6 in hippocampus kept stable in all the groups, its mRNA level raised obviously in 12h group. After 15-30 Gy whole-brain irradiation, the expression of some inflammatory cytokines increased abruptly in the hippocampus of SD rat within 1 day, but the interplay between inflammatory cytokines changes and the pathogenesis of radiation injury was incompletely understood at present. (authors)

  1. Long-term effects of whole brain radiation on intellectual function in children with medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Uozumi, Akimasa; Okimura, Yoshitaka; Ohsato, Katsunobu; Yamaura, Akira; Hasegawa, Keiko (Chiba Univ. (Japan). School of Medicine)

    1992-10-01

    Neuropsychological tests were administered to four children 4 to 10 years after treatment of medulloblastoma with surgery, radiation, and natural alpha-interferon. The age at the time of treatment ranged from 2 years and 4 months to 11 years. The radiation doses were 26-34 Gy to the whole brain, 48-52 Gy to the posterior fossa and 26-34 Gy to the whole spine. Uneventful follow-up periods ranged from 4 years and 8 months to 10 years and 6 months. At present they attend regular classes at local schools. The neuropsychological tests used were: Wechsler Intelligence Scale for Children-Revised (WISC-R), Frostig developmental test of visual perception and Uchida-Kraepelin psychometric test. The WISC-R showed a marked decrease of full-scale IQ in two of the four children (scores of 72 and 73). Their performance IQ scores were significantly lower than their verbal scores. This may reflect less ability to manage visual and spatial information than verbal information. The other two patients had full-scale IQ scores of 91 and 92 (within the normal range). The test of visual perception showed decreased ability in the three patients who were younger than 8 years, of age at the time of treatment but normal ability in the child who had been treated at 11 years of age. The Uchida-Kraepelin test showed reduced amounts of work accomplished and poor learning ability in all four patients. These findings suggest that intellectual function in children with medulloblastoma is affected by the failure of visual perception to develop normally because of whole brain radiation at an early age and that their problem is aggravated by secondary learning difficulties. It is necessary to provide these patients with individual learning programs based on the results of neuropsychological evaluations. (author).

  2. The PPARα Agonist Fenofibrate Preserves Hippocampal Neurogenesis and Inhibits Microglial Activation After Whole-Brain Irradiation

    International Nuclear Information System (INIS)

    Ramanan, Sriram; Kooshki, Mitra; Zhao Weiling; Hsu, F.-C.; Riddle, David R.; Robbins, Mike E.

    2009-01-01

    Purpose: Whole-brain irradiation (WBI) leads to cognitive impairment months to years after radiation. Numerous studies suggest that decreased hippocampal neurogenesis and microglial activation are involved in the pathogenesis of WBI-induced brain injury. The goal of this study was to investigate whether administration of the peroxisomal proliferator-activated receptor (PPAR) α agonist fenofibrate would prevent the detrimental effect of WBI on hippocampal neurogenesis. Methods and Materials: For this study, 129S1/SvImJ wild-type and PPARα knockout mice that were fed either regular or 0.2% wt/wt fenofibrate-containing chow received either sham irradiation or WBI (10-Gy single dose of 137 Cs γ-rays). Mice were injected intraperitoneally with bromodeoxyuridine to label the surviving cells at 1 month after WBI, and the newborn neurons were counted at 2 months after WBI by use of bromodeoxyuridine/neuronal nuclei double immunofluorescence. Proliferation in the subgranular zone and microglial activation were measured at 1 week and 2 months after WBI by use of Ki-67 and CD68 immunohistochemistry, respectively. Results: Whole-brain irradiation led to a significant decrease in the number of newborn hippocampal neurons 2 months after it was performed. Fenofibrate prevented this decrease by promoting the survival of newborn cells in the dentate gyrus. In addition, fenofibrate treatment was associated with decreased microglial activation in the dentate gyrus after WBI. The neuroprotective effects of fenofibrate were abolished in the knockout mice, indicating a PPARα-dependent mechanism or mechanisms. Conclusions: These data highlight a novel role for PPARα ligands in improving neurogenesis after WBI and offer the promise of improving the quality of life for brain cancer patients receiving radiotherapy.

  3. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    International Nuclear Information System (INIS)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J.

    2011-01-01

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  4. Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping

    Energy Technology Data Exchange (ETDEWEB)

    Nishiyama, Yuichi; Mori, Hiroshi; Katsube, Takashi; Kitagaki, Hajime [Shimane University Faculty of Medicine, Department of Radiology, Izumo-shi, Shimane (Japan); Kanayama, Hidekazu; Tada, Keiji; Yamamoto, Yasushi [Shimane University Hospital, Department of Radiology, Izumo-shi, Shimane (Japan); Takeshita, Haruo [Shimane University Faculty of Medicine, Department of Legal Medicine, Izumo-shi, Shimane (Japan); Kawakami, Kazunori [Fujifilm RI Pharma, Co., Ltd., Tokyo (Japan)

    2017-06-15

    This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. (orig.)

  5. Early Expansion of the Intracranial CSF Volume After Palliative Whole-Brain Radiotherapy: Results of a Longitudinal CT Segmentation Analysis

    International Nuclear Information System (INIS)

    Sanghera, Paul; Gardner, Sandra L.; Scora, Daryl; Davey, Phillip

    2010-01-01

    Purpose: To assess cerebral atrophy after radiotherapy, we measured intracranial cerebrospinal fluid volume (ICSFV) over time after whole-brain radiotherapy (WBRT) and compared it with published normal-population data. Methods and Materials: We identified 9 patients receiving a single course of WBRT (30 Gy in 10 fractions over 2 weeks) for ipsilateral brain metastases with at least 3 years of computed tomography follow-up. Segmentation analysis was confined to the tumor-free hemi-cranium. The technique was semiautomated by use of thresholds based on scanned image intensity. The ICSFV percentage (ratio of ICSFV to brain volume) was used for modeling purposes. Published normal-population ICSFV percentages as a function of age were used as a control. A repeated-measures model with cross-sectional (between individuals) and longitudinal (within individuals) quadratic components was fitted to the collected data. The influence of clinical factors including the use of subependymal plate shielding was studied. Results: The median imaging follow-up was 6.25 years. There was an immediate increase (p < 0.0001) in ICSFV percentage, which decelerated over time. The clinical factors studied had no significant effect on the model. Conclusions: WBRT immediately accelerates the rate of brain atrophy. This longitudinal study in patients with brain metastases provides a baseline against which the potential benefits of more localized radiotherapeutic techniques such as radiosurgery may be compared.

  6. Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping

    International Nuclear Information System (INIS)

    Nishiyama, Yuichi; Mori, Hiroshi; Katsube, Takashi; Kitagaki, Hajime; Kanayama, Hidekazu; Tada, Keiji; Yamamoto, Yasushi; Takeshita, Haruo; Kawakami, Kazunori

    2017-01-01

    This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. (orig.)

  7. Increasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid

    Directory of Open Access Journals (Sweden)

    Ryan C. Bates

    2015-08-01

    Full Text Available Neural tissue exposure to valproic acid (VPA increases several pro-survival phospho-proteins that can be used as biomarkers for indicating a beneficial drug response (pAktSer473, pGSK3βSer9, pErk1/2Thr202/Tyr204. Unfortunately, targeting VPA to neural tissue is a problem due to severe asymmetrical distribution, wherein the drug tends to remain in peripheral blood rather than localizing within the brain. Intracerebral delivery of an amide-linked VPA–PEG conjugate could address these issues by enhancing retention and promoting cerebro-global increases in pro-survival phospho-proteins. It is necessary to assay for the retained bioactivity of a PEGylated valproic acid molecule, along with locating an intracranial cannula placement that optimizes the increase of a known downstream biomarker for chronic VPA exposure. Here we show an acute injection of VPA–PEG conjugate within brain tissue increased virtually all of the assayed phospho-proteins, including well-known pro-survival factors. In contrast, an acute injection of VPA expectedly decreased signaling throughout the hour. Needle penetration into whole brain tissue is the intentional cause of trauma in this procedure. The trauma to brain tissue was observed to overcome known phospho-protein increases for unmodified VPA in the injected solution, while VPA–PEG conjugate appeared to induce significant increases in pro-survival phospho-proteins, despite the procedural trauma.

  8. Do patients with a limited number of brain metastases need whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, D.; Schild, S.E.

    2012-01-01

    Background: About 40% of patients with brain metastases have a very limited number of lesions and may be candidates for radiosurgery. Radiosurgery alone is superior to whole-brain radiotherapy (WBRT) alone for control of treated and new brain metastases. In patients with a good performance status, radiosurgery also resulted in better survival. However, the question is whether the results of radiosurgery alone can be further improved with additional WBRT. Methods: Information for this review was compiled by searching the PubMed and MEDLINE databases. Very important published meeting abstracts were also considered. Results: Based on both retrospective and prospective studies, the addition of WBRT to radiosurgery improved control of treated and new brain metastases but not survival. However, because a recurrence within the brain has a negative impact on neurocognitive function, it is important to achieve long-term control of brain metastases. Conclusion: The addition of WBRT provides significant benefits. Further randomized studies including adequate assessment of neurocognitive function and a follow-up period of at least 2 years are needed to help customize the treatment for individual patients. (orig.)

  9. Novel MRI methodology to detect human whole-brain connectivity changes after ingestion of fructose or glucose

    Science.gov (United States)

    Tsao, Sinchai; Wilkins, Bryce; Page, Kathleen A.; Singh, Manbir

    2012-03-01

    A novel MRI protocol has been developed to investigate the differential effects of glucose or fructose consumption on whole-brain functional brain connectivity. A previous study has reported a decrease in the fMRI blood oxygen level dependent (BOLD) signal of the hypothalamus following glucose ingestion, but due to technical limitations, was restricted to a single slice covering the hypothalamus, and thus unable to detect whole-brain connectivity. In another previous study, a protocol was devised to acquire whole-brain fMRI data following food intake, but only after restricting image acquisition to an MR sampling or repetition time (TR) of 20s, making the protocol unsuitable to detect functional connectivity above 0.025Hz. We have successfully implemented a continuous 36-min, 40 contiguous slices, whole-brain BOLD acquisition protocol on a 3T scanner with TR=4.5s to ensure detection of up to 0.1Hz frequencies for whole-brain functional connectivity analysis. Human data were acquired first with ingestion of water only, followed by a glucose or fructose drink within the scanner, without interrupting the scanning. Whole-brain connectivity was analyzed using standard correlation methodology in the 0.01-0.1 Hz range. The correlation coefficient differences between fructose and glucose ingestion among targeted regions were converted to t-scores using the water-only correlation coefficients as a null condition. Results show a dramatic increase in the hypothalamic connectivity to the hippocampus, amygdala, insula, caudate and the nucleus accumben for fructose over glucose. As these regions are known to be key components of the feeding and reward brain circuits, these results suggest a preference for fructose ingestion.

  10. Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

    International Nuclear Information System (INIS)

    Prokic, Vesna; Wiedenmann, Nicole; Fels, Franziska; Schmucker, Marianne; Nieder, Carsten; Grosu, Anca-Ligia

    2013-01-01

    Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 ± 0.62 Gy and 6.29 ± 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 ± 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 ± 0.7 Gy and 32.7 ± 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 ± 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

  11. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-04-01

    This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

  12. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-01-01

    Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

  13. Prognosis of patients treated with whole brain radiation therapy for metastatic gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Schechter, Naomi R.; Mychalczak, Borys; Jones, Walter; Spriggs, David

    1996-01-01

    Purpose/Objective: To evaluate the effect of multiple treatment and disease related variables on the local control and survival of patients receiving whole brain radiation therapy for metastatic gestational trophoblastic disease. Materials and Methods: Between November 1967 and December 1994, 21 patients were treated at our institution for gestational trophoblastic disease metastatic to the brain. 29% ((6(21))) were diagnosed with their brain metastases before the onset of chemotherapy (early group). 79% ((15(21))) developed their brain metastases during or after the administration of first-line chemotherapy (late group). All patients were treated with whole brain radiation therapy. The total dose ranged from 200 cGy to 3600 cGy (median 2200 cGy). Sixteen patients (76%) received concurrent systemic chemotherapy. None of the patients received intrathecal chemotherapy as a component of their initial treatment. Survival and local control were calculated from the date of diagnosis of brain metastases. Follow-up ranged from 11 months to 170 months with a median of 77 months. Results: The median overall survival was 21 months, with 2- and 5-year actuarial survivals of 46% and 31%, respectively. Neither survival nor local control was significantly affected by age at diagnosis of brain metastases (<35 vs. ≥35 years), time of presentation of brain metastases (early vs. late), or use of concurrent chemotherapy. The total dose of radiation (<2200 cGy vs. ≥2200 cGy) significantly affected initial local control, but not survival. The 5-year actuarial local control of the initial brain metastases with ≥2200 cGy was 91%, as compared to 24% with <2200 cGy (p=0.05). Survival was significantly affected by control of disease at extracranial sites. The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100% and 83%, respectively, as compared to 8% and 0% for the 12 whose extracranial disease was not controlled (p=0

  14. Whole brain, high resolution spin-echo resting state fMRI using PINS multiplexing at 7 T

    NARCIS (Netherlands)

    Koopmans, P.J.; Boyacioglu, R.; Barth, M.; Norris, David Gordon

    2012-01-01

    This article demonstrates the application of spin-echo EPI for resting state fMRI at 7 T. A short repetition time of 1860 ms was made possible by the use of slice multiplexing which permitted whole brain coverage at high spatial resolution (84 slices of 1.6 mm thickness). Radiofrequency power

  15. The evaluation of lens absorbed dose according to the optimold for whole brain radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yong Mo; Park, Byoung Suk; Ahn, Jong Ho; Song, Ki Won [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    In the current whole brain Radiation Therapy, Optimold was used to immobilize the head. However, skin dose was increased about 22% due to the scattering radiation by the Optimold. Since the minimum dose causing cataracts was 2 Gy, it could be seen that the effects were large especially on the lens. Therefore, in the whole brain Radiation Therapy, it was to compare and to evaluate the lens absorbed dose according to the presence of Optimold in the eyeball part. In order to compare and to evaluate the lens absorbed dose according to the presence of Optimold in the eyeball part, the Optimold mask was made up to 5 mm bolus on the part of the eye lens in the human model phantom (Anderson Rando Phantom, USA). In the practice treatment, to measure the lens dose, the simulation therapy was processed by placing the GafChromic EBT3 film under bolus, and after the treatment plan was set up through the treatment planning system (Pinnacle, PHILIPS, USA), the treatments were measured repeatedly three times in the same way. After removing the Optimold mask in the eyeball part, it was measured in the same way as above. After scanning the film and measuring the dose by using the Digital Flatbed Scanner (Expression 10000XL, EPSON, USA), the doses were compared and evaluated according to the presence of Optimold mask in the eyeball part. When there was the Optimold mask in the eyeball part, it was measured at 10.2cGy ± 1.5 in the simulation therapy, and at 24.8cGy ± 2.7 in the treatment, and when the Optimold mask was removed in the eye part, it was measured at 12.9cGy ± 2.2 in the simulation therapy, and at 17.6cGy ± 1.5 in the treatment. In case of removing the Optimold mask in the eyeball part, the dose was increased approximately 3cGy in the simulation therapy and was reduced approximately 7cGy in the treatment in comparison to the case that the Optimold mask was not removed. During the whole treatment, since the lens absorbed dose was reduced about 27%, the chance to cause

  16. The evaluation of lens absorbed dose according to the optimold for whole brain radiation therapy

    International Nuclear Information System (INIS)

    Yang, Yong Mo; Park, Byoung Suk; Ahn, Jong Ho; Song, Ki Won

    2014-01-01

    In the current whole brain Radiation Therapy, Optimold was used to immobilize the head. However, skin dose was increased about 22% due to the scattering radiation by the Optimold. Since the minimum dose causing cataracts was 2 Gy, it could be seen that the effects were large especially on the lens. Therefore, in the whole brain Radiation Therapy, it was to compare and to evaluate the lens absorbed dose according to the presence of Optimold in the eyeball part. In order to compare and to evaluate the lens absorbed dose according to the presence of Optimold in the eyeball part, the Optimold mask was made up to 5 mm bolus on the part of the eye lens in the human model phantom (Anderson Rando Phantom, USA). In the practice treatment, to measure the lens dose, the simulation therapy was processed by placing the GafChromic EBT3 film under bolus, and after the treatment plan was set up through the treatment planning system (Pinnacle, PHILIPS, USA), the treatments were measured repeatedly three times in the same way. After removing the Optimold mask in the eyeball part, it was measured in the same way as above. After scanning the film and measuring the dose by using the Digital Flatbed Scanner (Expression 10000XL, EPSON, USA), the doses were compared and evaluated according to the presence of Optimold mask in the eyeball part. When there was the Optimold mask in the eyeball part, it was measured at 10.2cGy ± 1.5 in the simulation therapy, and at 24.8cGy ± 2.7 in the treatment, and when the Optimold mask was removed in the eye part, it was measured at 12.9cGy ± 2.2 in the simulation therapy, and at 17.6cGy ± 1.5 in the treatment. In case of removing the Optimold mask in the eyeball part, the dose was increased approximately 3cGy in the simulation therapy and was reduced approximately 7cGy in the treatment in comparison to the case that the Optimold mask was not removed. During the whole treatment, since the lens absorbed dose was reduced about 27%, the chance to cause

  17. Global cerebral blood flow changes measured by brain perfusion SPECT immediately after whole brain irradiation

    International Nuclear Information System (INIS)

    Ohtawa, Nobuyuki; Machida, Kikuo; Honda, Norinari; Hosono, Makoto; Takahashi, Takeo

    2003-01-01

    Whole brain irradiation (WBI) is still a major treatment option for patients with metastatic brain tumor despite recent advances in chemotherapy and newer techniques of radiation therapy. Cerebral blood flow (CBF) of changes induced by whole brain radiation is not fully investigated, and the aim of the study was to measure CBF changes non-invasively with brain perfusion SPECT to correlate with treatment effect or prognosis. Total of 106 patients underwent WBI during April 1998 to March 2002. Both brain MRI and brain perfusion SPECT could be performed before (less than 1 week before or less than 10 Gy of WBI) and immediately after (between 1 week before and 2 weeks after the completion of WBI) the therapy in 17 of these patients. They, 10 men and 7 women, all had metastatic brain tumor with age range of 45 to 87 (mean of 61.4) years. Tc-99m brain perfusion agent (HMPAO in 4, ECD in 13) was rapidly administered in a 740-MBq dose to measure global and regional CBF according to Matsuda's method, which based on both Patlak plot and Lassens' linearity correction. Brain MRI was used to measure therapeutic response according to World Health Organization (WHO) classification as complete remission (CR), partial response (PR), no change (NC), and progressive disease (PD). Survival period was measured from the completion of WBI. Mean global CBF was 40.6 and 41.5 ml/100 g/min before and immediately after the WBI, respectively. Four patients increased (greater than 10%) their global mean CBF, 10 unchanged (less than 10% increase or decrease), and 3 decreased after the WBI. The WBI achieved CR in none, PR in 8, NC in 6, and PD in 3 on brain MRI. Change in global mean CBF (mean±SD) was significantly larger in PR (4.3±2.0 ml/100 g/min, p=0.002) and in NC (-0.1±4.5) than in PD (-3.9±6.4, P=0.002, P=0.016, respectively). Survival was not significantly (p>0.05) different among the patients with CR (20 weeks), NC (48 weeks), and PD (21 weeks). Change in global CBF and survival was

  18. A study of whole brain perfusion CT and CT angiography in hyperacute and acute cerebral infarction

    International Nuclear Information System (INIS)

    Zhang Yonghai; Bai Junhu; Zhang Ming; Yang Guocai; Tang Guibo; Fang Jun; Shi Wei; Li Xinghua; Liu Suping; Lu Qing; Tang Jun

    2005-01-01

    Objective: To evaluate the diagnostic value of whole-brain perfusion blood volume-weighted CT imaging (PWCT) and simultaneous CT angiography (CTA) on early stage of cerebral ischemic infarction. Methods: Non-contrast CT (NCCT), CT perfusion-weighted imaging (PWCT) and delayed CT (DCT) were conducted on 20 cases of early ischemic infarction of whose onset time ranged from 2 to 24 hours. All cases were reexamined with CT or MRI one week to one month later. CT values and perfusion blood volume (PBV) of central and peripheral low perfusion areas as well as those of collateral side were measured. CTA was reconstructed with PWCT as source images to evaluate occlusion or stenosis of blood vessel, and DCT was used to detect the collateral circulation. Results: Of the 20 cases, NCCT, PWCT and CTA were negative in 10 cases in which 6 were confirmed as Transient Ischemic Attack (TIA) on reexamined CT and clinical features, and the other 4 were confirmed as lacunar infarction. For the remaining 10 cases, a comparison was made with ANOVA between low perfusion area (central, peripheral inside and outside) and collateral side. The difference was significant (P<0.01). However, no significant difference was revealed in the central, peripheral inside and outside areas. PBV values were significant in low perfusion area and collateral side (P<0.05). The area of the final infarction was larger than that of the low perfusion area, and the percentage of enlargement exhibited medium negative correlation to the time of ischemia. CTA indicated that 2 cases suffered from left middle cerebral artery occlusion, meanwhile anterior and middle branches of MCA in the other 3 cases were not identified. The sensitivity of NCCT, PWCT and CTA were 28.5%, 71.4% and 35.7% respectively. DCT indicated that 5 cases had asymmetrical blood vessels. Conclusion: The whole-brain perfusion-weighted CT imaging and simultaneous CT angiography (CTA) is p roved to be a simple, timesaving and effective method for the

  19. Repeat Whole Brain Radiation Therapy with a Simultaneous Infield Boost: A Novel Technique for Reirradiation

    International Nuclear Information System (INIS)

    Hall, W.A.; Prabhu, R.S.; Crocker, I.R.; Dhabban, A.; Ogunleye, T.; Kandula, Sh.; Jiang, X.; Curran, W.J.; Shu, H.G.

    2014-01-01

    The treatment of patients who experience intracranial progression after whole brain radiation therapy (WBRT) is a clinical challenge. Novel radiation therapy delivery technologies are being applied with the objective of improving tumor and symptom control in these patients. The purpose of this study is to describe the clinical outcomes of the application of a novel technology to deliver repeat WBRT with volume modulated arc therapy (VMAT) and a simultaneous infield boost (WB-SIB) to gross disease. A total of 16 patients were initially treated with WBRT between 2000 and 2008 and then experienced intracranial progression, were treated using repeat WB-SIB, and were analyzed. The median dose for the first course of WBRT was 35 Gy (range: 30–50.4 Gy). Median time between the initial course of WBRT and repeat WB-SIB was 11.3 months. The median dose at reirradiation was 20 Gy to the whole brain with a median boost dose of 30 Gy to gross disease. A total of 2 patients demonstrated radiographic disease progression after treatment. The median overall survival (OS) time from initial diagnosis of brain metastases was 18.9 months (range: 7.1–66.6 (95% CI: 0.8–36.9)). The median OS time after initiation of reirradiation for all patients was 2.7 months (range: 0.46–14.46 (95% CI: 1.3–8.7)). Only 3 patients experienced CTCAE grade 3 fatigue. No other patients experienced any ≥ CTCAE grade 3 toxicity. This analysis reports the result of a novel RT delivery technique for the treatment of patients with recurrent brain metastases. Side effects were manageable and comparable to other conventional repeat WBRT series. Repeat WB-SIB using the VMAT RT delivery technology is feasible and appears to have acceptable short-term acute toxicity. These results may provide a foundation for further exploration of the WB-SIB technique for repeat WBRT in future prospective clinical trials.

  20. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    Science.gov (United States)

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The whole-brain N-acetylaspartate correlates with education in normal adults.

    Science.gov (United States)

    Glodzik, Lidia; Wu, William E; Babb, James S; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U; Gass, Achim; Gonen, Oded

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. The Prospects of Whole Brain Emulation within the next Half- Century

    Science.gov (United States)

    Eth, Daniel; Foust, Juan-Carlos; Whale, Brandon

    2013-12-01

    Whole Brain Emulation (WBE), the theoretical technology of modeling a human brain in its entirety on a computer-thoughts, feelings, memories, and skills intact-is a staple of science fiction. Recently, proponents of WBE have suggested that it will be realized in the next few decades. In this paper, we investigate the plausibility of WBE being developed in the next 50 years (by 2063). We identify four essential requisite technologies: scanning the brain, translating the scan into a model, running the model on a computer, and simulating an environment and body. Additionally, we consider the cultural and social effects of WBE. We find the two most uncertain factors for WBE's future to be the development of advanced miniscule probes that can amass neural data in vivo and the degree to which the culture surrounding WBE becomes cooperative or competitive. We identify four plausible scenarios from these uncertainties and suggest the most likely scenario to be one in which WBE is realized, and the technology is used for moderately cooperative ends

  3. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    International Nuclear Information System (INIS)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio

    2001-01-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  4. Whole brain magnetization transfer histogram analysis of pediatric acute lymphoblastic leukemia patients receiving intrathecal methotrexate therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Akira [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: yakira@kuhp.kyoto-u.ac.jp; Miki, Yukio [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: mikiy@kuhp.kyoto-u.ac.jp; Adachi, Souichi [Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto-shi Kyoto 606-8507 (Japan)]. E-mail: sadachi@kuhp.kyoto-u.ac.jp (and others)

    2006-03-15

    Background and purpose: The purpose of this prospective study was to evaluate the hypothesis that magnetization transfer ratio (MTR) histogram analysis of the whole brain could detect early and subtle brain changes nonapparent on conventional magnetic resonance imaging (MRI) in children with acute lymphoblastic leukemia (ALL) receiving methotrexate (MTX) therapy. Materials and methods: Subjects in this prospective study comprised 10 children with ALL (mean age, 6 years; range, 0-16 years). In addition to conventional MRI, magnetization transfer images were obtained before and after intrathecal and intravenous MTX therapy. MTR values were calculated and plotted as a histogram, and peak height and location were calculated. Differences in peak height and location between pre- and post-MTX therapy scans were statistically analyzed. Conventional MRI was evaluated for abnormal signal area in white matter. Results: MTR peak height was significantly lower on post-MTX therapy scans than on pre-MTX therapy scans (p = 0.002). No significant differences in peak location were identified between pre- and post-chemotherapy imaging. No abnormal signals were noted in white matter on either pre- or post-MTX therapy conventional MRI. Conclusions: This study demonstrates that MTR histogram analysis allows better detection of early and subtle brain changes in ALL patients who receive MTX therapy than conventional MRI.

  5. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

    Directory of Open Access Journals (Sweden)

    Sagari Sarkar

    Full Text Available The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD have significantly increased fractional anisotropy (FA of the uncinate fasciculus (a white matter (WM tract that connects the amygdala to the frontal lobe compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear.We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history.The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1 the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2 right superior longitudinal fasciculus; and 3 left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone.Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

  6. Whole-brain serial-section electron microscopy in larval zebrafish.

    Science.gov (United States)

    Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

    2017-05-18

    High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

  7. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

    Science.gov (United States)

    Sarkar, Sagari; Dell'Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C; Deeley, Quinton; Murphy, Declan G M

    2016-01-01

    The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

  8. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    Science.gov (United States)

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Hippocampal Neuron Number Is Unchanged 1 Year After Fractionated Whole-Brain Irradiation at Middle Age

    International Nuclear Information System (INIS)

    Shi Lei; Molina, Doris P.; Robbins, Michael E.; Wheeler, Kenneth T.; Brunso-Bechtold, Judy K.

    2008-01-01

    Purpose: To determine whether hippocampal neurons are lost 12 months after middle-aged rats received a fractionated course of whole-brain irradiation (WBI) that is expected to be biologically equivalent to the regimens used clinically in the treatment of brain tumors. Methods and Materials: Twelve-month-old Fischer 344 X Brown Norway male rats were divided into WBI and control (CON) groups (n = 6 per group). Anesthetized WBI rats received 45 Gy of 137 Cs γ rays delivered as 9 5-Gy fractions twice per week for 4.5 weeks. Control rats were anesthetized but not irradiated. Twelve months after WBI completion, all rats were anesthetized and perfused with paraformaldehyde, and hippocampal sections were immunostained with the neuron-specific antibody NeuN. Using unbiased stereology, total neuron number and the volume of the neuronal and neuropil layers were determined in the dentate gyrus, CA3, and CA1 subregions of hippocampus. Results: No differences in tissue integrity or neuron distribution were observed between the WBI and CON groups. Moreover, quantitative analysis demonstrated that neither total neuron number nor the volume of neuronal or neuropil layers differed between the two groups for any subregion. Conclusions: Impairment on a hippocampal-dependent learning and memory test occurs 1 year after fractionated WBI at middle age. The same WBI regimen, however, does not lead to a loss of neurons or a reduction in the volume of hippocampus

  10. Whole-brain functional magnetic resonance imaging of cerebral arteriovenous malformations involving the motor pathways

    International Nuclear Information System (INIS)

    Ozdoba, C.; Remonda, L.; Loevblad, K.O.; Schroth, G.; Nirkko, A.C.

    2002-01-01

    To investigate cortical, basal ganglia and cerebellar activation in patients with arteriovenous malformations (AVMs) involving the motor pathways, we studied ten patients (six male, four female, mean age 30.3 years, range 7.4-44.1) by whole-brain functional magnetic resonance imaging (fMRI) in a 1.5-T scanner with the EPI-BOLD-technique. In seven cases multiple fMRI studies were available, acquired in the course of the multi-session endovascular interventional treatment. Self-paced right- and left-handed finger-tapping tasks were used to invoke activation. In six patients a super-selective amytal test (Wada test) was performed during diagnostic pre-interventional angiography studies. Abnormal cortical activation patterns, with activation of the primary sensorimotor area, the supplementary motor area and/or the cerebellum shifted to unphysiological locations, were found in four patients. In all cases, localization of the AVM could account for the changes from the normal. After endovascular procedures, fMRI demonstrated shifts in the activation pattern in three patients. In the six patients that had undergone fMRI studies and the Wada test, both methods yielded comparable results. The fact that AVMs are structural anomalies for which the brain can partly compensate ('plasticity') was underlined by these results. fMRI is a valuable tool in the pre-therapeutic evaluation and post-interventional follow-up of patients with cerebral AVMs in whom an operation or an endovascular procedure is planned. (orig.)

  11. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    Directory of Open Access Journals (Sweden)

    Tallet Agnes V

    2012-05-01

    Full Text Available Abstract Whole brain radiation therapy (WBRT is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more, insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation.

  12. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment

    International Nuclear Information System (INIS)

    Tallet, Agnes V; Azria, David; Barlesi, Fabrice; Spano, Jean-Philippe; Carpentier, Antoine F; Gonçalves, Antony; Metellus, Philippe

    2012-01-01

    Whole brain radiation therapy (WBRT) is an effective treatment in brain metastases and, when combined with local treatments such as surgery and stereotactic radiosurgery, gives the best brain control. Nonetheless, WBRT is often omitted after local treatment due to its potential late neurocognitive effects. Publications on radiation-induced neurotoxicity have used different assessment methods, time to assessment, and definition of impairment, thus making it difficult to accurately assess the rate and magnitude of the neurocognitive decline that can be expected. In this context, and to help therapeutic decision making, we have conducted this literature review, with the aim of providing an average incidence, magnitude and time to occurrence of radio-induced neurocognitive decline. We reviewed all English language published articles on neurocognitive effects of WBRT for newly diagnosed brain metastases or with a preventive goal in adult patients, with any methodology (MMSE, battery of neurcognitive tests) with which baseline status was provided. We concluded that neurocognitive decline is predominant at 4 months, strongly dependant on brain metastases control, partially solved at later time, graded 1 on a SOMA-LENT scale (only 8% of grade 2 and more), insufficiently assessed in long-term survivors, thus justifying all efforts to reduce it through irradiation modulation

  13. Stereotactic irradiation without whole-brain irradiation for single brain metastasis

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Takamura, Akio; Tomita, Masayoshi; Suzuki, Keishiro; Nishioka, Takashi; Isu, Toyohiko; Kato, Tsutomu; Sawamura, Yutaka; Miyamachi, Keikichi; Abe, Hiroshi; Miyasaka, Kazuo

    1997-01-01

    Purpose: The effectiveness of stereotactic irradiation (STI) alone without whole-brain irradiation (WBI) for a single metastatic brain tumor was analyzed retrospectively. Methods and Materials: Forty-four patients with this condition were treated using radiosurgery (RS) alone or fractionated stereotactic radiotherapy (FSR) without WBI. Results: The initial response rate was 92% and the overall local control rate was 84% (37 of 44 patients). A total of 39% (18 of 44) of patients experienced intracranial relapse outside the initial target area. Forty-eight percent (21 of 44) of patients required salvage treatment for intracranial relapse. All 7 patients who received WBI as salvage treatment required no further salvage treatment, but 5 of the 14 patients who received salvage STI without WBI required three to four treatments for brain metastasis. Late radiation damage was not seen with initial treatment but was observed with retreatment. The overall median survival time was 261 days, with a standard error of 64 days. Actuarial survival at 12 and 24 months was 34% and 9%, respectively. The actuarial survival rate was significantly affected by the existence of active extracranial disease (p = 0.041). Conclusion: The high response rate and short treatment period of STI alone are advantageous in the treatment of single brain metastasis in patients with active extracranial disease with WBI reserved for relapse. Because of the low complication rate, STI alone may be also useful in patients with good prognosis, without extracranial disease

  14. Support vector machine-based classification of Alzheimer's disease from whole-brain anatomical MRI

    International Nuclear Information System (INIS)

    Magnin, Benoit; Mesrob, Lilia; Kinkingnehun, Serge; Pelegrini-Issac, Melanie; Colliot, Olivier; Sarazin, Marie; Dubois, Bruno; Lehericy, Stephane; Benali, Habib

    2009-01-01

    We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with Alzheimer's disease (AD) and elderly control subjects. We studied 16 patients with AD [mean age ± standard deviation (SD)=74.1 ±5.2 years, mini-mental score examination (MMSE) = 23.1 ± 2.9] and 22 elderly controls (72.3±5.0 years, MMSE=28.5± 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results. We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%). Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD. (orig.)

  15. Outcome after whole brain radiotherapy alone in intracranial leptomeningeal carcinomatosis from solid tumors

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    Gani, C.; Mueller, A.C.; Eckert, F.; Schroeder, C.; Bamberg, M.; Berger, B. [Univ. of Tuebingen (Germany). Dept. of Radiation Oncology; Bender, B. [Univ. of Tuebingen (Germany). Dept. of Diagnostics and Interventional Neuroradiology; Pantazis, G. [Univ. of Tuebingen (Germany). Dept. of Neuropathology

    2012-02-15

    The purpose of the present study was to investigate outcome after whole brain radiotherapy (WBRT) alone as a palliative treatment without concomitant chemotherapy for intracranial leptomeningeal carcinomatosis (LMC). Overall survival and treatment response were retrospectively analyzed in 27 consecutive patients with LMC from breast and lung cancer. All patients had evidence of intracranial manifestations of LMC. Seven potential prognostic factors were evaluated. Median overall survival (OS) for the entire group was 8.1 weeks. OS rates after 6 and 12 months were 26% and 15%, respectively. Improvement of neurological deficits was observed in 3 patients. In 3 of 4 patients with follow-up MRI studies, a decreased size of contrast-enhanced lesions was observed. Prognostic factors for improved OS on univariate analysis were absence of cranial nerve dysfunction, Karnofsky Performance Score (KPS) > 60%, and time interval > 35 months between the initial diagnosis of malignant disease and development of LMC. On multivariate analysis, absence of cranial nerve dysfunction remained the only significant prognosticator for OS (median 3.7 vs. 19.4 weeks, p < 0.001). WBRT alone is an effective palliative treatment for patients unfit/unsuitable for chemotherapy and low performance status suffering from intracranial LMC. However, prognostic factors should be considered in order to identify patients who are likely to benefit from WBRT. (orig.)

  16. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Whole-brain structural connectivity in dyskinetic cerebral palsy and its association with motor and cognitive function.

    Science.gov (United States)

    Ballester-Plané, Júlia; Schmidt, Ruben; Laporta-Hoyos, Olga; Junqué, Carme; Vázquez, Élida; Delgado, Ignacio; Zubiaurre-Elorza, Leire; Macaya, Alfons; Póo, Pilar; Toro, Esther; de Reus, Marcel A; van den Heuvel, Martijn P; Pueyo, Roser

    2017-09-01

    Dyskinetic cerebral palsy (CP) has long been associated with basal ganglia and thalamus lesions. Recent evidence further points at white matter (WM) damage. This study aims to identify altered WM pathways in dyskinetic CP from a standardized, connectome-based approach, and to assess structure-function relationship in WM pathways for clinical outcomes. Individual connectome maps of 25 subjects with dyskinetic CP and 24 healthy controls were obtained combining a structural parcellation scheme with whole-brain deterministic tractography. Graph theoretical metrics and the network-based statistic were applied to compare groups and to correlate WM state with motor and cognitive performance. Results showed a widespread reduction of WM volume in CP subjects compared to controls and a more localized decrease in degree (number of links per node) and fractional anisotropy (FA), comprising parieto-occipital regions and the hippocampus. However, supramarginal gyrus showed a significantly higher degree. At the network level, CP subjects showed a bilateral pathway with reduced FA, comprising sensorimotor, intraparietal and fronto-parietal connections. Gross and fine motor functions correlated with FA in a pathway comprising the sensorimotor system, but gross motor also correlated with prefrontal, temporal and occipital connections. Intelligence correlated with FA in a network with fronto-striatal and parieto-frontal connections, and visuoperception was related to right occipital connections. These findings demonstrate a disruption in structural brain connectivity in dyskinetic CP, revealing general involvement of posterior brain regions with relative preservation of prefrontal areas. We identified pathways in which WM integrity is related to clinical features, including but not limited to the sensorimotor system. Hum Brain Mapp 38:4594-4612, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  19. Diagnostic performance of whole brain volume perfusion CT in intra-axial brain tumors: Preoperative classification accuracy and histopathologic correlation

    International Nuclear Information System (INIS)

    Xyda, Argyro; Haberland, Ulrike; Klotz, Ernst; Jung, Klaus; Bock, Hans Christoph; Schramm, Ramona; Knauth, Michael; Schramm, Peter

    2012-01-01

    Background: To evaluate the preoperative diagnostic power and classification accuracy of perfusion parameters derived from whole brain volume perfusion CT (VPCT) in patients with cerebral tumors. Methods: Sixty-three patients (31 male, 32 female; mean age 55.6 ± 13.9 years), with MRI findings suspected of cerebral lesions, underwent VPCT. Two readers independently evaluated VPCT data. Volumes of interest (VOIs) were marked circumscript around the tumor according to maximum intensity projection volumes, and then mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability Ktrans perfusion datasets. A second VOI was placed in the contra lateral cortex, as control. Correlations among perfusion values, tumor grade, cerebral hemisphere and VOIs were evaluated. Moreover, the diagnostic power of VPCT parameters, by means of positive and negative predictive value, was analyzed. Results: Our cohort included 32 high-grade gliomas WHO III/IV, 18 low-grade I/II, 6 primary cerebral lymphomas, 4 metastases and 3 tumor-like lesions. Ktrans demonstrated the highest sensitivity, specificity and positive predictive value, with a cut-off point of 2.21 mL/100 mL/min, for both the comparisons between high-grade versus low-grade and low-grade versus primary cerebral lymphomas. However, for the differentiation between high-grade and primary cerebral lymphomas, CBF and CBV proved to have 100% specificity and 100% positive predictive value, identifying preoperatively all the histopathologically proven high-grade gliomas. Conclusion: Volumetric perfusion data enable the hemodynamic assessment of the entire tumor extent and provide a method of preoperative differentiation among intra-axial cerebral tumors with promising diagnostic accuracy.

  20. Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

    International Nuclear Information System (INIS)

    Addeo, Raffaele; Caraglia, Michele; Faiola, Vincenzo; Capasso, Elena; Vincenzi, Bruno; Montella, Liliana; Guarrasi, Rosario; Caserta, Luigi; Del Prete, Salvatore

    2007-01-01

    Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions

  1. Treatment of small cell carcinoma of lung with combined high dose mediastinal irradiation, whole brain prophylaxis and chemotherapy

    International Nuclear Information System (INIS)

    Shank, B.; Natale, R.B.; Hilaris, B.S.; Wittes, R.E.

    1981-01-01

    Survival of patients with small cell carcinoma of lung, treated on a new combined radiotherapy-chemotherapy protocol, compares favorably with other regimens in the literature and our own previous combined approaches. Radiation, given after induction chemotherapy, consisted of whole brain prophylaxis in all 44 evaluable patients. Patients with limited disease were also treated to the primary and mediastinum to a high dose (5000 rad equivalent) using multiple fields. The new chemotherapy regimen consisted of induction with cyclophosphamide, doxorubicin, and vincristine alternated with cis-platinum and VP-16 (an epipodophyllotoxin) for two cycles, followed by consolidation with low dose cyclophosphamide and vincristine concurrent with irradiation. Patients with limited disease who achieved less than complete response, and all patients with extensive disease were not continued on maintenance chemotherapy. Out of 24 evaluable patients with limited disease, there was 73% survival at 1 year by life-table analysis, measured from treatment initiation. After induction, 16/24 of these limited disease patients were CR (complete responders): 20/24 were CR at completion of their irradiation. Out of 20 evaluable patients with extensive disease, there was 59% survival at 1 year by life-table analysis. Only 4/44 (9%) brain parenchymal relapses occurred, one at 3 months and one at 6 months after local failure and two in patients who did not become CRs, implicating a possible re-seeding mechanism. Five patients had central nervous system relapses outside of brain parenchyma (spinal epidural and leptomeningeal); in three patients this was the initial site of failure. Significant complications included leukopenia (50%) and thrombocytopenia (24%) primarily during induction, and chronic pulmonary fibrosis (25%), possibly contributing to two deaths

  2. High-speed imaging at 3 tesla. A technical and clinical review with an emphasis on whole-brain 3D imaging

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Kawai, Hisashi; Fukatsu, Hiroshi; Ishigaki, Takeo; Komada, Tomomi

    2005-01-01

    Improvements to the inherently high specific-absorption rate (SAR) of high-speed imaging at 3T are necessary in order to render this method clinically feasible. Various efforts have been undertaken to improve the associated hardware and software. In this review, we focus on whole-brain isotropic 3D imaging with a turbo spin-echo sequence with variable flip-angle echo trains (3D-TSE-VFL) and present its technical and clinical features. This sequence can be used to acquire images of various contrasts including T 2 -weighted, fat-suppressed T 2 -weighted, fluid-attenuated inversion recovery (FLAIR), fat-suppressed FLAIR, and STIR (short tau inversion recovery). Various aspects of 3D-TSE-VFL are discussed, including CSF (cerebrospinal fluid) and metal artifacts, STIR contrast, small-part visualization other than brain, and the possibility of serial subtraction. Some images from clinical cases are presented. (author)

  3. Whole brain resting-state analysis reveals decreased functional connectivity in major depression

    Directory of Open Access Journals (Sweden)

    Ilya M. Veer

    2010-09-01

    Full Text Available Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within six months before inclusion and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxelwise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: 1 decreased bilateral amygdala and left anterior insula connectivity in an affective network, 2 reduced connectivity of the left frontal pole in a network associated with attention and working memory, and 3 decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or grey matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

  4. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

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    Hauswald Henrik

    2012-08-01

    Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

  5. Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

    International Nuclear Information System (INIS)

    Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won

    2011-01-01

    Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

  6. Fast 3D magnetic resonance fingerprinting for a whole-brain coverage.

    Science.gov (United States)

    Ma, Dan; Jiang, Yun; Chen, Yong; McGivney, Debra; Mehta, Bhairav; Gulani, Vikas; Griswold, Mark

    2018-04-01

    The purpose of this study was to accelerate the acquisition and reconstruction time of 3D magnetic resonance fingerprinting scans. A 3D magnetic resonance fingerprinting scan was accelerated by using a single-shot spiral trajectory with an undersampling factor of 48 in the x-y plane, and an interleaved sampling pattern with an undersampling factor of 3 through plane. Further acceleration came from reducing the waiting time between neighboring partitions. The reconstruction time was accelerated by applying singular value decomposition compression in k-space. Finally, a 3D premeasured B 1 map was used to correct for the B 1 inhomogeneity. The T 1 and T 2 values of the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI phantom showed a good agreement with the standard values, with an average concordance correlation coefficient of 0.99, and coefficient of variation of 7% in the repeatability scans. The results from in vivo scans also showed high image quality in both transverse and coronal views. This study applied a fast acquisition scheme for a fully quantitative 3D magnetic resonance fingerprinting scan with a total acceleration factor of 144 as compared with the Nyquist rate, such that 3D T 1 , T 2 , and proton density maps can be acquired with whole-brain coverage at clinical resolution in less than 5 min. Magn Reson Med 79:2190-2197, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  7. Evaluating the morphological changes of intracranial arteries and whole-brain perfusion in undetermined isolated vertigo.

    Science.gov (United States)

    Li, Wenxian; Feng, Youzhen; Lu, Weibiao; Xie, Xie; Xiong, Zhilin; Jing, Zhen; Cai, Xiangran; Huang, Li'an

    2016-11-15

    To determine the morphological changes of intracranial arteries and whole-brain perfusion in undetermined isolated vertigo (UIV) patients using 320-detector row computed tomography (CT). A total of 150 patients who underwent CT angiography (CTA) and CT perfusion (CTP) imaging were divided into UIV group and benign paroxysmal positional vertigo (BPPV) group. Sixty individuals with sex- and age-matched without vertigo and cerebral diseases served as the control. The morphological changes of intracranial arteries, perfusion parameters and vascular risk factors (VRFs) were analyzed, calculated and compared. In UIV patients, hypertension (HT), hyperlipidemia and number of VRFs≥3 occurred more commonly (P<0.0125, respectively). The incidence of vertebral artery dominance (VAD), vertebral artery stenosis (VAS) and basilar artery curvature (BAC) were significantly higher (P<0.0125, respectively). HT was an independent risk predictor of non-VAD (OR: 5.411, 95%CI: 1.401; 20.900, P=0.014). HT and VAD associated with BAC served as risk predictors (OR: 4.081, 95%CI: 1.056;15.775, P=0.041 and OR: 6.284, 95%CI: 1.848; 21.365, P=0.003, respectively). The absolute difference in relative values of CTP parameters from cerebellum and brainstem were significantly different (P<0.05), and hypoperfusion was found in the territories of the non-VAD side and the BAC cohort (P<0.05, respectively). On the basis of multiple VRFs, morphological changes of vertebrobasilar artery (VBA) and the unilateral hypoperfusion of the cerebellum and brainstem, that acts as a herald for IV occurrence, which should be paid cautious attention to UIV patients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. SU-E-QI-12: Morphometry Based Measurements of the Structural Response to Whole Brain Radiation

    International Nuclear Information System (INIS)

    Fuentes, D; Castillo, R; Castillo, E; Guerrero, T

    2014-01-01

    Purpose: Although state of the art radiation therapy techniques for treating intracranial malignancies have eliminated acute brain injury, cognitive impairment occurs in 50–90% of patients who survive >6mo post irradiation. Quantitative characterization of therapy response is needed to facilitate therapeutic strategies to minimize radiation induced cognitive impairment [1]. Deformation based morphometry techniques [2, 3] are presented as a quantitative imaging biomarker of therapy response in patients receiving whole brain radiation for treating medulloblastoma. Methods: Post-irradiation magnetic resonance imaging (MRI) data sets were retrospectively analyzed in N=15 patients, >60 MR image datasets. As seen in Fig 1(a), volume changes at multiple time points post-irradiation were quantitatively measured in the cerebrum and ventricles with respect to pre-irradiation MRI. A high resolution image Template, was registered to the pre-irradiation MRI of each patient to create a brain atlas for the cerebrum, cerebellum, and ventricles. Skull stripped images for each patient were registered to the initial pre-treatment scan. Average volume changes in the labeled regions were measured using the determinant of the displacement field Jacobian. Results: Longitudinal measurements, Fig 1(b-c), show a negative correlation p=.06, of the cerebral volume change with the time interval from irradiation. A corresponding positive correlation, p=.01, between ventricular volume change and time interval from irradiation is seen. One sample t-test for correlations were computed using a Spearman method. An average decrease in cerebral volume, p=.08, and increase in ventricular volume, p<.001, was observed. The radiation dose was seen directly proportional to the induced volume changes in the cerebrum, r=−.44, p<.001, Fig 1(d). Conclusion: Results indicate that morphometric monitoring of brain tissue volume changes may potentially be used to quantitatively assess toxicity and response to

  9. Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

    International Nuclear Information System (INIS)

    Welzel, Grit; Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

    2008-01-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects

  10. Clustering of Whole-Brain White Matter Short Association Bundles Using HARDI Data

    Directory of Open Access Journals (Sweden)

    Claudio Román

    2017-12-01

    Full Text Available Human brain connectivity is extremely complex and variable across subjects. While long association and projection bundles are stable and have been deeply studied, short association bundles present higher intersubject variability, and few studies have been carried out to adequately describe the structure, shape, and reproducibility of these bundles. However, their analysis is crucial to understand brain function and better characterize the human connectome. In this study, we propose an automatic method to identify reproducible short association bundles of the superficial white matter, based on intersubject hierarchical clustering. The method is applied to the whole brain and finds representative clusters of similar fibers belonging to a group of subjects, according to a distance metric between fibers. We experimented with both affine and non-linear registrations and, due to better reproducibility, chose the results obtained from non-linear registration. Once the clusters are calculated, our method performs automatic labeling of the most stable connections based on individual cortical parcellations. We compare results between two independent groups of subjects from a HARDI database to generate reproducible connections for the creation of an atlas. To perform a better validation of the results, we used a bagging strategy that uses pairs of groups of 27 subjects from a database of 74 subjects. The result is an atlas with 44 bundles in the left hemisphere and 49 in the right hemisphere, of which 33 bundles are found in both hemispheres. Finally, we use the atlas to automatically segment 78 new subjects from a different HARDI database and to analyze stability and lateralization results.

  11. SU-E-QI-12: Morphometry Based Measurements of the Structural Response to Whole Brain Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes, D; Castillo, R; Castillo, E; Guerrero, T [UT MD Anderson Cancer Center, Houston, TX (United States)

    2014-06-15

    Purpose: Although state of the art radiation therapy techniques for treating intracranial malignancies have eliminated acute brain injury, cognitive impairment occurs in 50–90% of patients who survive >6mo post irradiation. Quantitative characterization of therapy response is needed to facilitate therapeutic strategies to minimize radiation induced cognitive impairment [1]. Deformation based morphometry techniques [2, 3] are presented as a quantitative imaging biomarker of therapy response in patients receiving whole brain radiation for treating medulloblastoma. Methods: Post-irradiation magnetic resonance imaging (MRI) data sets were retrospectively analyzed in N=15 patients, >60 MR image datasets. As seen in Fig 1(a), volume changes at multiple time points post-irradiation were quantitatively measured in the cerebrum and ventricles with respect to pre-irradiation MRI. A high resolution image Template, was registered to the pre-irradiation MRI of each patient to create a brain atlas for the cerebrum, cerebellum, and ventricles. Skull stripped images for each patient were registered to the initial pre-treatment scan. Average volume changes in the labeled regions were measured using the determinant of the displacement field Jacobian. Results: Longitudinal measurements, Fig 1(b-c), show a negative correlation p=.06, of the cerebral volume change with the time interval from irradiation. A corresponding positive correlation, p=.01, between ventricular volume change and time interval from irradiation is seen. One sample t-test for correlations were computed using a Spearman method. An average decrease in cerebral volume, p=.08, and increase in ventricular volume, p<.001, was observed. The radiation dose was seen directly proportional to the induced volume changes in the cerebrum, r=−.44, p<.001, Fig 1(d). Conclusion: Results indicate that morphometric monitoring of brain tissue volume changes may potentially be used to quantitatively assess toxicity and response to

  12. The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma

    International Nuclear Information System (INIS)

    Goyal, Lav K.; Suh, John H.; Reddy, Chandana A.; Barnett, Gene H.

    2000-01-01

    Purpose: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). Methods and Materials: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. Results: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). Conclusion: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion

  13. Late vascular effects of whole brain X-irradiation in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Yoshii, Y [Tsukuba Univ., Sakma, Ibaraki (Japan). Inst. of Clinical Medicine; Phillips, T L [California Univ., San Francisco (USA). Dept. of Radiation Oncology

    1982-01-01

    The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min/sup -1/ (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

  14. Late vascular effects of whole brain X-irradiation in the mouse

    International Nuclear Information System (INIS)

    Yoshii, Y.; Phillips, T.L.

    1982-01-01

    The whole brains of mice were irradiated with 250kVp X-rays at 120 rads min -1 (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain section. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectactic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis. (Author)

  15. Scalp Dose Evaluation According Radiation Therapy Technique of Whole Brain Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Joon Yung; Park, Soo Yun; Kim, Jong Sik; Choi, Byeong Gi; Song, Gi Won [Dept. of Radiation Oncology, Samsung Medical Center, Seoul (Korea, Republic of)

    2011-09-15

    Opposing portal irradiation with helmet field shape that has been given to a patient with brain metastasis can cause excess dose in patient's scalp, resulting in hair loss. For this reason, this study is to quantitatively analyze scalp dose for effective prevention of hair loss by comparing opposing portal irradiation with scalp-shielding shape and tomotherapy designed to protect patient's scalp with conventional radiation therapy. Scalp dose was measured by using three therapies (HELMET, MLC, TOMO) after five thermo-luminescence dosimeters were positioned along center line of frontal lobe by using RANDO Phantom. Scalp dose and change in dose distribution were compared and analyzed with DVH after radiation therapy plan was made by using Radiation Treatment Planning System (Pinnacle3, Philips Medical System, USA) and 6 MV X-ray (Clinac 6EX, VARIAN, USA). When surface dose of scalp by using thermo-luminescence dosimeters was measured, it was revealed that scalp dose decreased by average 87.44% at each point in MLC technique and that scalp dose decreased by average 88.03% at each point in TOMO compared with HELMET field therapy. In addition, when percentage of volume (V95%, V100%, V105% of prescribed dose) was calculated by using Dose Volume Histogram (DVH) in order to evaluate the existence or nonexistence of hotspot in scalp as to three therapies (HELMET, MLC, TOMO), it was revealed that MLC technique and TOMO plan had good dose coverage and did not have hot spot. Reducing hair loss of a patient who receives whole brain radiotherapy treatment can make a contribution to improve life quality of the patient. It is expected that making good use of opposing portal irradiation with scalp-shielding shape and tomotherapy to protect scalp of a patient based on this study will reduce hair loss of a patient.

  16. A computational study of whole-brain connectivity in resting state and task fMRI

    Science.gov (United States)

    Goparaju, Balaji; Rana, Kunjan D.; Calabro, Finnegan J.; Vaina, Lucia Maria

    2014-01-01

    Background We compared the functional brain connectivity produced during resting-state in which subjects were not actively engaged in a task with that produced while they actively performed a visual motion task (task-state). Material/Methods In this paper we employed graph-theoretical measures and network statistics in novel ways to compare, in the same group of human subjects, functional brain connectivity during resting-state fMRI with brain connectivity during performance of a high level visual task. We performed a whole-brain connectivity analysis to compare network statistics in resting and task states among anatomically defined Brodmann areas to investigate how brain networks spanning the cortex changed when subjects were engaged in task performance. Results In the resting state, we found strong connectivity among the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral parietal cortex, and hippocampal formation, consistent with previous reports of the default mode network (DMN). The connections among these areas were strengthened while subjects actively performed an event-related visual motion task, indicating a continued and strong engagement of the DMN during task processing. Regional measures such as degree (number of connections) and betweenness centrality (number of shortest paths), showed that task performance induces stronger inter-regional connections, leading to a denser processing network, but that this does not imply a more efficient system as shown by the integration measures such as path length and global efficiency, and from global measures such as small-worldness. Conclusions In spite of the maintenance of connectivity and the “hub-like” behavior of areas, our results suggest that the network paths may be rerouted when performing the task condition. PMID:24947491

  17. Accumulation of neuronal DNA damage as an early covariate of determinant of death after whole-brain irradiaton

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Weinstein, R.E.

    1979-01-01

    The state of the DNA from cerebellar neurons of male Sprague-Dawley rats after whole-brain irradiation with 2000 rad of x rays was determined at various times by obtaining DNA sedimentation profiles using alkaline sucrose gradients in slow reorienting zonal rotors. It took more than 4 weeks after irradiation for the neuronal DNA distributions to return to those obtained from the unirradiated controls. At 7 weeks, the DNA from irradiated neurons sedimented more rapidly than that from unirradiated neurons. Accumulation of the neuronal DNA damage (degradation.) which led to slower sedimenting DNA species began by Week 10 and continued until the majority of the irradiated rats began to die at Week 20. We propose as a working hypothesis that the accumulation of neuronal DNA damage initially observed 10 weeks after 2000 rad of whole-brain irradiation may reflect or cause changes in the central nervous system that later result in the death of the animal

  18. Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone

    International Nuclear Information System (INIS)

    Rowe, John D. del; Bello, Jacqueline; Mitnick, Robin; Sood, Brij; Filippi, Christopher; Moran, Justin Ph.D.; Freeman, Katherine; Mendez, Frances; Bases, Robert

    1999-01-01

    Purpose: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. Methods and Materials: The organ distribution of 3 H lucanthone in mice and 125 I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. Results: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. Conclusion: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536

  19. Analysis and evalaution in the production process and equipment area of the low-cost solar array project. [including modifying gaseous diffusion and using ion implantation

    Science.gov (United States)

    Goldman, H.; Wolf, M.

    1979-01-01

    The manufacturing methods for photovoltaic solar energy utilization are assessed. Economic and technical data on the current front junction formation processes of gaseous diffusion and ion implantation are presented. Future proposals, including modifying gaseous diffusion and using ion implantation, to decrease the cost of junction formation are studied. Technology developments in current processes and an economic evaluation of the processes are included.

  20. Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

    Science.gov (United States)

    Başar, Erol

    2005-01-01

    According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

  1. Full scale IQ (FSIQ) changes in children treated with whole brain and partial brain irradiation. A review and analysis

    International Nuclear Information System (INIS)

    Fuss, M.; Poljanc, K.; Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA

    2000-01-01

    The purpose of this analysis was to assess current knowledge, with focus on correlation with radiation dose, irradiated volume and age. Method: Full Scale IQ (FSIQ) data, representing 1,938 children, were derived from 36 publications and analyzed as to radiation dose, irradiated volume, and age. Results: FSIQ after whole brain irradiation showed a non-linear decline as dosage increased. The dose-effect relationship was age-related, with more pronounced FSIQ decline at younger age. FSIQ test results below the normal level ( 50 Gy. Conclusion: The collected data suggest that whole brain irradiation doses of 18 and 24 Gy have no major impact on intellectual outcome in children older than age 6, but may cause impairment in younger children. Doses >24 Gy comprise a substantial risk for FSIQ decline, even in older children. At equal dose levels, partial brain irradiation is less damaging than whole brain irradiation. The authors are well aware of limitations in the interpretation of data collected for the current review. (orig.) [de

  2. Appearance and impact of post-operative intracranial clips and coils on whole-brain CT angiography and perfusion

    International Nuclear Information System (INIS)

    Roach, Cayce J.; Russell, Cheryl L.; Hanson, Eric H.; Bluett, Brent; Orrison, William W.

    2012-01-01

    Background: To evaluate the effect of vascular clips and endovascular coils placed for intracranial aneurysms and arteriovenous malformations on whole-brain computed tomography (CT) angiography and perfusion. Methods: A 320-detector row dynamic volume CT system imaged 11 patients following surgical placement of vascular clips or endovascular coils. The extent of clip and coil subtraction by automated software was evaluated using CT digital subtraction angiography and CT perfusion. Impact on CT perfusion values by retained intracranial devices was compared to age- and gender-matched controls. Results: Clip and coil subtraction on CT angiography was graded as good in 8 and moderate in 3 cases. A residual neck and additional aneurysm were noted in 1 of 11 patients. Post-procedural axial slice level CT perfusion values decreased in reliability with increasing proximity to the metallic devices secondary to beam hardening. However, the intracranial devices did not affect axial slice level CTP values of cerebral blood volume, cerebral blood flow and mean transit time outside of the level of the device. Time to peak values was globally decreased outside of the immediate vascular intervention region. Conclusions: Advances in CT technology have provided clinically useful subtraction of intracranial clips and coils. While CT perfusion values were altered in device subtraction areas and within beam hardening artifact areas; they can provide valuable postoperative information on whole-brain hemodynamics. In selected cases, the combination of CT angiography and whole-brain CT perfusion can offer an alternative to conventional angiography that is a more invasive option.

  3. Mean field diffusion models for precipitation in crystalline GaAs including surface tension and bulk stresses

    Energy Technology Data Exchange (ETDEWEB)

    Dreyer, Wolfgang [Weierstrass-Institut fuer Angewandte Analysis und Stochastik (WIAS) im Forschungsverbund Berlin e.V. (Germany); Kimmerle, Sven-Joachim [Humboldt-Univ. Berlin (Germany). Dept. of Mathematics

    2009-07-01

    Based on a thermodynamically consistent model for precipitation in gallium arsenide crystals including surface tension and bulk stresses by Dreyer and Duderstadt, we propose different mathematical models to describe the size evolution of liquid droplets in a crystalline solid. The first class of models treats the diffusion-controlled regime of interface motion, while the second class is concerned with the interface-controlled regime of interface motion. Our models take care of conservation of mass and substance. We consider homogenised models, where different length scales of the experimental situation have been exploited in order to simplify the equations. These homogenised models generalise the well-known Lifshitz-Slyozov-Wagner model for Ostwald ripening. Mean field models capture the main properties of our system and are well adapted for numerics and further analysis. Numerical evidence suggests in which case which one of the two regimes might be appropriate to the experimental situation. (orig.)

  4. Focal Pancreatitis Mimicking Pancreatic Mass: Magnetic Resonance Imaging (MRI)/Magnetic Resonance Cholangiopancreatography (MRCP) Findings Including Diffusion-Weighted MRI

    International Nuclear Information System (INIS)

    Momtahen, A.J.; Balci, N.C.; Alkaade, S.; Akduman, E.I.; Burton, F.R.

    2008-01-01

    Background: Focal pancreatitis (FP) is a confined inflammation that mimics a pancreatic mass. Its imaging diagnosis is important to avoid unnecessary procedures. Purpose: To describe the spectrum of magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and diffusion-weighted MRI (DWI) findings of focal pancreatitis mimicking pancreatic masses. Material and Methods: Findings of MRI/MRCP including DWI with a b value of 0 and 600 s/mm2 in 14 patients with pancreatic masses on MRI were retrospectively reviewed and compared to normal pancreas in 14 patients as a control group. Results: FP revealed hypointense signal intensity (SI) (3/14), hypo- to isointense SI (7/14), or isointense SI (4/14) on T1-weighted images, and hypointense SI (1/14), isointense SI (5/14), iso- to hyperintense SI (7/14), or hyperintense SI (1/14) on T2-weighted images compared to remaining pancreas (RP). MRCP images revealed dilatation of the common bile duct (CBD) and main pancreatic duct (MPD) (5/14), dilatation of the MPD only (3/14), dilatation of the CBD only (3/14), and normal MPD and CBD (3/14). Both FP and RP revealed three types of time-signal intensity curves: 1) rapid rise to a peak, with a rapid decline (FP=2, RP=4), 2) slow rise to a peak, followed by a slow decline (FP=5, RP=4), and 3) slower rise to a peak, with a slow decline or plateau (FP=7, RP=6). Mean apparent diffusion coefficient (ADC) values for FP and RP were 2.09±0.18 and 2.03±0.2x10 -3 mm 2 /s, respectively. ADC values of FP and RP revealed no significant difference. Conclusion: The spectrum of imaging findings of focal pancreatitis on MRI/MRCP including DWI was described. Findings of FP were not distinctive as compared to the remaining pancreas

  5. Craniospinal versus whole brain irradiation in Medulloblastoma patients, with introduction of utilizing a simple immobilization device

    Directory of Open Access Journals (Sweden)

    Haddad P

    2001-05-01

    Full Text Available Craniospinal irradiation plus posterior fossa boost (CS1 is the standard modality of post-operative treatment of patient with medulloblastoma, but considering the technical difficulties and limited facilities, often whole- brain irradiation plus posterior fossa boost (WBI had been used in our institution until 1991. Tust a retrospective study was undertaken to compare the patients treated by By WBI and CSI for recurrences and disease-free survival (DFS. Files of all medullobalstoma patients treated post-operatively in our department in the 10 – year period of 1986-1996 were reviewed. To obtain the best possible follow- up, a formal inquiry letter was mailed to all patients’ addresses.Total of 72 patients had been treated, with a mean age of 14.7 years and male-to-female ratio of 1.5:1 Thirty –seven patients had been treated by WBI and 35 by CS. A simple wooden device designed and made in our department was used for CSI patients’ set-up and immobilization. Mean radiation dose to posterior fossa was 4, 765 cGy in WBT and 5, 071 cGY in CSI (180-200 cGy fractions. Sixty-two patients (85% came back for follow-up, with 24 recurrences. Only 24% of CSI patients had recurrences, versus 51% in WBI Nearly all Wbi recurrences versus half of the CSI recurrences were spinal. DFS was 39 months in CSI and 26 months in WBI (P<0.001 . in multi-factorial analysis, only the extent of radiation (CSI versus WBI, P<0.001 was statistically significant. Mean age in our patients was higher than what is commonly reported in literature. The immobilization device introduce was a simple and useful accessory to CSI. Considering DFS, CSI in our department was acceptabley comparable to literature results and significantly superior to WBI. With regard to relatively high spinal recurrence rate even in CSI, the importance of suitable spinal cytological and imaging evaluation is again emphasized.

  6. Minocycline ameliorates cognitive impairment induced by whole-brain irradiation: an animal study

    International Nuclear Information System (INIS)

    Zhang, Liyuan; Li, Kun; Sun, Rui; Zhang, Yuan; Ji, JianFeng; Huang, Peigeng; Yang, Hongying; Tian, Ye

    2014-01-01

    It has been long recognized that cranial irradiation used for the treatment of primary and metastatic brain tumor often causes neurological side-effects such as intellectual impairment, memory loss and dementia, especially in children patients. Our previous study has demonstrated that whole-brain irradiation (WBI) can cause cognitive decline in rats. Minocycline is an antibiotic that has shown neuroprotective properties in a variety of experimental models of neurological diseases. However, whether minocycline can ameliorate cognitive impairment induced by ionizing radiation (IR) has not been tested. Thus this study aimed to demonstrate the potential implication of minocycline in the treatment of WBI-induced cognitive deficits by using a rat model. Sprague Dawley rats were cranial irradiated with electron beams delivered by a linear accelerator with a single dose of 20 Gy. Minocycline was administered via oral gavages directly into the stomach before and after irradiation. The open field test was used to assess the anxiety level of rats. The Morris water maze (MWM) was used to assess the spatial learning and memory of rats. The level of apoptosis in hippocampal neurons was measured using immunohistochemistry for caspase-3 and relative markers for mature neurons (NeuN) or for newborn neurons (Doublecortin (DCX)). Neurogenesis was determined by BrdU incorporation method. Neither WBI nor minocycline affected the locomotor activity and anxiety level of rats. However, compared with the sham-irradiated controls, WBI caused a significant loss of learning and memory manifest as longer latency to reach the hidden platform in the MWM task. Minocycline intervention significantly improved the memory retention of irradiated rats. Although minocycline did not rescue neurogenesis deficit caused by WBI 2 months post-IR, it did significantly decreased WBI-induced apoptosis in the DCX positive neurons, thereby resulting in less newborn neuron depletion 12 h after irradiation

  7. Model brain based learning (BBL and whole brain teaching (WBT in learning

    Directory of Open Access Journals (Sweden)

    Baiq Sri Handayani

    2017-08-01

    Full Text Available The learning process is a process of change in behavior as a form of the result of learning. The learning model is a crucial component of the success of the learning process. The learning model is growing fastly, and each model has different characteristics. Teachers are required to be able to understand each model to teach the students optimally by matching the materials and the learning model. The best of the learning model is the model that based on the brain system in learning that are the model of Brain Based Learning (BBL and the model of Whole Brain Teaching (WBT. The purposes of this article are to obtain information related to (1 the brain’s natural learning system, (2 analyze the characteristics of the model BBL and WBT based on theory, brain sections that play a role associated with syntax, similarities, and differences, (3 explain the distinctive characteristics of both models in comparison to other models. The results of this study are: (1 the brain’s natural learning system are: (a the nerves in each hemisphere do not work independently, (b doing more activities can connect more brain nerves, (c the right hemisphere controls the left side motoric sensor of the body, and vice versa; (2 the characteristics of BBL and WBT are: (a BBL is based on the brain’s structure and function, while the model WBT is based on the instructional approach, neurolinguistic, and body language, (b the parts of the brain that work in BBL are: cerebellum, cerebral cortex, frontal lobe, limbic system, and prefrontal cortex; whereas the parts that work WBT are: prefrontal cortex, visual cortex, motor cortex, limbic system, and amygdala, (c the similarities between them are that they both rely on the brain’s system and they both promote gesture in learning, whereas the differences are on the view of the purposes of gestures and the learning theory that they rely on. BBL relies on cognitive theory while WBT relies on social theory; (3 the typical

  8. Comparison of proton therapy techniques for treatment of the whole brain as a component of craniospinal radiation.

    Science.gov (United States)

    Dinh, Jeffrey; Stoker, Joshua; Georges, Rola H; Sahoo, Narayan; Zhu, X Ronald; Rath, Smruti; Mahajan, Anita; Grosshans, David R

    2013-12-17

    For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT. Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36 Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student's t-test with Bonferroni corrections to account for multiple comparisons. Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 ± 14 vs. 97.4 ± 5, p left; 24.8 ± 0.8 vs. 22.2 ± 0.7, p right; 25.2 ± 0.8 vs. 22.8 ± 0.7, p vs. PSWO (mean cochlea dose Gy(RBE): 36.4 ± 0.2 vs. 36.7 ± 0.1, p = NS). Moreover, dose homogeneity was inferior in PSW plans in comparison to PSWO plans as reflected by significant alterations in both whole brain and brainstem homogeneity index (HI) and inhomogeneity coefficient (IC). In comparison to both PSPT techniques, multi-field optimized intensity modulated (MFO-IMPT) spot scanning treatment plans displayed superior sparing of both lens and cochlea (max lens: 12.5 ± 0.6 and 12.9 ± 0.7 right and left respectively; mean cochlea 28.6

  9. Comparison of proton therapy techniques for treatment of the whole brain as a component of craniospinal radiation

    International Nuclear Information System (INIS)

    Dinh, Jeffrey; Stoker, Joshua; Georges, Rola H; Sahoo, Narayan; Zhu, X Ronald; Rath, Smruti; Mahajan, Anita; Grosshans, David R

    2013-01-01

    For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT. Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36 Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student’s t-test with Bonferroni corrections to account for multiple comparisons. Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 ± 14 vs. 97.4 ± 5, p < 0.05). As predicted, PSWO plans had significantly higher lens exposure in comparison to PSW plans (max lens dose Gy(RBE): left; 24.8 ± 0.8 vs. 22.2 ± 0.7, p < 0.05, right; 25.2 ± 0.8 vs. 22.8 ± 0.7, p < 0.05). However, PSW plans demonstrated no significant cochlear sparing vs. PSWO (mean cochlea dose Gy(RBE): 36.4 ± 0.2 vs. 36.7 ± 0.1, p = NS). Moreover, dose homogeneity was inferior in PSW plans in comparison to PSWO plans as reflected by significant alterations in both whole brain and brainstem homogeneity index (HI) and inhomogeneity coefficient (IC). In comparison to both PSPT techniques, multi-field optimized intensity modulated (MFO-IMPT) spot

  10. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole 1

    Science.gov (United States)

    Tucker, Joseph E.; Mauzerall, David; Tucker, Edward B.

    1989-01-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water. PMID:16666864

  11. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole.

    Science.gov (United States)

    Tucker, J E; Mauzerall, D; Tucker, E B

    1989-07-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water.

  12. A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Caravatta, Luciana; Deodato, Francesco; Ferro, Marica [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Massaccesi, Mariangela [Department of Radiation Oncology, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Cilla, Savino [Medical Physics Unit, Fondazione di Ricerca e Cura ' Giovanni Paolo II,' Universita Cattolica del S. Cuore, Campobasso (Italy); Padula, Gilbert D.A. [Department of Radiation Oncology, The Lacks Cancer Center Saint Mary' s Health Care, Grand Rapids, Michigan (United States); Mignogna, Samantha; Tambaro, Rosa [Department of Palliative Therapies, Fondazione di Ricerca e Cura ' Giovanni Paolo II' , Universita Cattolica del S. Cuore, Campobasso (Italy); Carrozza, Francesco [Department of Oncology, A. Cardarelli Hospital, Campobasso (Italy); Flocco, Mariano [Madre Teresa di Calcutta Hospice, Larino (Italy); Cantore, Giampaolo [Department of Neurological Sciences, Istituto Neurologico Mediterraneo Neuromed, Istituto di Ricovero e Cura a Carattere Scientifico, Pozzilli (Italy); Scapati, Andrea [Department of Radiation Oncology, ' San Francesco' Hospital, Nuoro (Italy); Buwenge, Milly [Department of Radiotherapy, Mulago Hospital, Kampala (Uganda); and others

    2012-11-15

    Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

  13. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial

    International Nuclear Information System (INIS)

    Fogarty, Gerald; Shivalingam, Brindha; Dhillon, Haryana; Thompson, John F; Morton, Rachael L; Vardy, Janette; Nowak, Anna K; Mandel, Catherine; Forder, Peta M; Hong, Angela; Hruby, George; Burmeister, Bryan

    2011-01-01

    Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete. This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function. Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain

  14. Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique.

    Science.gov (United States)

    Borghetti, Paolo; Pedretti, Sara; Spiazzi, Luigi; Avitabile, Rossella; Urpis, Mauro; Foscarini, Federica; Tesini, Giulia; Trevisan, Francesca; Ghirardelli, Paolo; Pandini, Sara Angela; Triggiani, Luca; Magrini, Stefano Maria; Buglione, Michela

    2016-04-19

    To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients. Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 "treatment plans" (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis. Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the "target coverage" was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5-2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS. This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature's preliminary data are confirming also a

  15. Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study

    International Nuclear Information System (INIS)

    Tsai, Ping-Fang; Yang, Chi-Cheng; Chuang, Chi-Cheng; Huang, Ting-Yi; Wu, Yi-Ming; Pai, Ping-Ching; Tseng, Chen-Kan; Wu, Tung-Ho; Shen, Yi-Liang; Lin, Shinn-Yn

    2015-01-01

    Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis might occur after WBRT. It is reported that conformal hippocampal sparing would provide the preservation of NCFs. Our study aims to investigate the hippocampal dosimetry and to demonstrate the correlation between hippocampal dosimetry and neurocognitive outcomes in patients receiving hippocampal sparing during WBRT (HS-WBRT). Forty prospectively recruited cancer patients underwent HS-WBRT for therapeutic or prophylactic purposes. Before receiving HS-WBRT, all participants received a battery of baseline neurocognitive assessment, including memory, executive functions and psychomotor speed. The follow-up neurocognitive assessment at 4 months after HS-WBRT was also performed. For the delivery of HS-WBRT, Volumetric Modulated Arc Therapy (VMAT) with two full arcs and two non-coplanar partial arcs was employed. For each treatment planning, dose volume histograms were generated for left hippocampus, right hippocampus, and the composite hippocampal structure respectively. Biologically equivalent doses in 2-Gy fractions (EQD 2 ) assuming an alpha/beta ratio of 2 Gy were computed. To perform analyses addressing the correlation between hippocampal dosimetry and the change in scores of NCFs, pre- and post-HS-WBRT neurocognitive assessments were available in 24 patients in this study. Scores of NCFs were quite stable before and after HS-WBRT in terms of hippocampus-dependent memory. Regarding verbal memory, the corresponding EQD 2 values of 0, 10, 50, 80 % irradiating the composite hippocampal structure with <12.60 Gy, <8.81, <7.45 Gy and <5.83 Gy respectively were significantly associated with neurocognitive preservation indicated by the immediate recall of Word List Test of Wechsler Memory Scale-III. According to logistic regression analyses, it was noted that

  16. Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique

    International Nuclear Information System (INIS)

    Borghetti, Paolo; Pedretti, Sara; Spiazzi, Luigi; Avitabile, Rossella; Urpis, Mauro; Foscarini, Federica; Tesini, Giulia; Trevisan, Francesca; Ghirardelli, Paolo; Pandini, Sara Angela; Triggiani, Luca; Magrini, Stefano Maria; Buglione, Michela

    2016-01-01

    To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients. Ten patients were treated with helical IMRT, 5 of them with SRS after whole brain radiotherapy (WBRT) and 5 with SIB. MRI co-registration with planning CT was mandatory and prescribed doses were 30 Gy in 10 fractions (fr) for WBRT and 15Gy/1fr or 45Gy/10fr in SRS or SIB, respectively. For each patient, 4 “treatment plans” (VMAT SRS and SIB, helical IMRT SRS and SIB) were calculated and accepted if PTV boost was included in 95 % isodose and dose constraints of the main organs at risk were respected without major deviations. Homogeneity Index (HI), Conformal Index (CI) and Conformal Number (CN) were considered to compare the different plans. Moreover, time of treatment delivery was calculated and considered in the analysis. Volume of brain metastasis ranged between 1.43 and 51.01 cc (mean 12.89 ± 6.37 ml) and 3 patients had double lesions. V95% resulted over 95 % in the average for each kind of technique, but the “target coverage” was inadequate for VMAT planning with two sites. The HI resulted close to the ideal value of zero in all cases; VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS showed mean CI of 2.15, 2.10, 2.44 and 1.66, respectively (optimal range: 1.5–2.0). Helical IMRT-SRS was related to the best and reliable finding of CN (0.66). The mean of treatment time was 210 s, 467 s, 440 s, 1598 s, respectively, for VMAT-SIB, VMAT-SRS, Helical IMRT-SIB and Helical IMRT-SRS. This dosimetric comparison show that helical IMRT obtain better target coverage and respect of CI and CN; VMAT could be acceptable in solitary metastasis. SIB modality can be considered as a good choice for clinical and logistic compliance; literature’s preliminary data are confirming

  17. Image quality, radiation dose and diagnostic accuracy of 70 kVp whole brain volumetric CT perfusion imaging: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Xiao Kun; Ni, Qian Qian; Zhou, Chang Sheng; Chen, Guo Zhong; Luo, Song; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Schoepf, U.J. [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Medical University of South Carolina, Ashley River Tower, Division of Cardiovascular Imaging, Charleston, SC (United States); Fuller, Stephen R.; De Cecco, Carlo N. [Medical University of South Carolina, Ashley River Tower, Division of Cardiovascular Imaging, Charleston, SC (United States)

    2016-11-15

    To evaluate image quality and diagnostic accuracy for acute infarct detection and radiation dose of 70 kVp whole brain CT perfusion (CTP) and CT angiography (CTA) reconstructed from CTP source data. Patients were divided into three groups (n = 50 each): group A, 80 kVp, 21 scanning time points; groups B, 70 kVp, 21 scanning time points; group C, 70 kVp, 17 scanning time points. Objective and subjective image quality of CTP and CTA were compared. Diagnostic accuracy for detecting acute infarct and cerebral artery stenosis ≥ 50 % was calculated for CTP and CTA with diffusion weighted imaging and digital subtraction angiography as reference standards. Effective radiation dose was compared. There were no differences in any perfusion parameter value between three groups (P > 0.05). No difference was found in subjective image quality between three groups (P > 0.05). Diagnostic accuracy for detecting acute infarct and vascular stenosis showed no difference between three groups (P > 0.05). Compared with group A, radiation doses of groups B and C were decreased by 28 % and 37 % (both P < 0.001), respectively. Compared with 80 kVp protocol, 70 kVp brain CTP allows comparable vascular and perfusion assessment and lower radiation dose while maintaining high diagnostic accuracy in detecting acute infarct. (orig.)

  18. Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?

    Science.gov (United States)

    Karlsson, Hanna; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

    2011-02-01

    Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

  19. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg

    International Nuclear Information System (INIS)

    Hintz, Mandy

    2017-01-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  20. Measurements of T1 and T2 over time in formalin-fixed human whole-brain specimens

    International Nuclear Information System (INIS)

    Tovi, M.; Ericsson, A.

    1992-01-01

    T1 and T2 were measured in 5 formalin-fixed human whole-brain specimens as a function of time. Gray matter/white matter contrast reversal was observed around the 4th day and was considered to be due to the greater decrease in T1 in gray than in white matter. A possible explanation for this is that the decomposition of the myelin phospholipid structure by formalin somewhat counteracts the general reductive effect of the fixation procedure on relaxation times. (orig.)

  1. Whole body MRI, including diffusion-weighted imaging in follow-up of patients with testicular cancer.

    Science.gov (United States)

    Mosavi, Firas; Laurell, Anna; Ahlström, Håkan

    2015-11-01

    Whole body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet the clinical utility of these techniques in follow-up of testicular cancer patients has not been evaluated. The purpose of this study was to evaluate the feasibility of WB MRI with continuous table movement (CTM) technique, including multistep DWI in follow-up of patients with testicular cancer. WB MRI including DWI was performed in follow-up of 71 consecutive patients (median age, 37 years; range 19-84) with histologically confirmed testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences using CTM technique. Furthermore, multi-step DWI was performed using b-value 50 and 1000 s/mm(2). One criterion for feasibility was patient tolerance and satisfactory image quality. Another criterion was the accuracy in detection of any pathological mass, compared to standard of reference. Signal intensity in DWI was used for evaluation of residual mass activity. Clinical, laboratory and imaging follow-up were applied as standard of reference for the evaluation of WB MRI. WB MRI was tolerated in nearly all patients (69/71 patients, 97%) and the image quality was satisfactory. Metal artifacts deteriorated the image quality in six patients, but it did not influence the overall results. No case of clinical relapse was observed during the follow-up time. There was a good agreement between conventional WB MRI and standard of reference in all patients. Three patients showed residual masses and DWI signal was not restricted in these patients. Furthermore, DWI showed abnormally high signal intensity in a normal-sized retroperitoneal lymph node indicating metastasis. The subsequent (18)F-FDG PET/CT could verify the finding. WB MRI with CTM technique including multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI may contribute to important added-value data to conventional MRI sequences

  2. Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation.

    Science.gov (United States)

    Li, Jin-Rui; Zhang, Ye; Zheng, Jia-Lian

    2016-07-01

    The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT.

  3. Parotid gland sparing effect by computed tomography-based modified lower field margin in whole brain radiotherapy

    International Nuclear Information System (INIS)

    Cho, Oyeon; Chun, Mi Son; Oh, Young Taek; Kim, Mi Hwa; Park, Hae Jin; Nam, Sang Soo; Heo, Jae Sung; Noh, O Kyu; Park, Sung Ho

    2013-01-01

    Parotid gland can be considered as a risk organ in whole brain radiotherapy (WBRT). The purpose of this study is to evaluate the parotid gland sparing effect of computed tomography (CT)-based WBRT compared to 2-dimensional plan with conventional field margin. From January 2008 to April 2011, 53 patients underwent WBRT using CT-based simulation. Bilateral two-field arrangement was used and the prescribed dose was 30 Gy in 10 fractions. We compared the parotid dose between 2 radiotherapy plans using different lower field margins: conventional field to the lower level of the atlas (CF) and modified field fitted to the brain tissue (MF). Averages of mean parotid dose of the 2 protocols with CF and MF were 17.4 Gy and 8.7 Gy, respectively (p 98% of prescribed dose were 99.7% for CF and 99.5% for MF. Compared to WBRT with CF, CT-based lower field margin modification is a simple and effective technique for sparing the parotid gland, while providing similar dose coverage of the whole brain.

  4. High-resolution whole-brain DCE-MRI using constrained reconstruction: Prospective clinical evaluation in brain tumor patients

    International Nuclear Information System (INIS)

    Guo, Yi; Zhu, Yinghua; Lingala, Sajan Goud; Nayak, Krishna; Lebel, R. Marc; Shiroishi, Mark S.; Law, Meng

    2016-01-01

    Purpose: To clinically evaluate a highly accelerated T1-weighted dynamic contrast-enhanced (DCE) MRI technique that provides high spatial resolution and whole-brain coverage via undersampling and constrained reconstruction with multiple sparsity constraints. Methods: Conventional (rate-2 SENSE) and experimental DCE-MRI (rate-30) scans were performed 20 minutes apart in 15 brain tumor patients. The conventional clinical DCE-MRI had voxel dimensions 0.9 × 1.3 × 7.0 mm 3 , FOV 22 × 22 × 4.2 cm 3 , and the experimental DCE-MRI had voxel dimensions 0.9 × 0.9 × 1.9 mm 3 , and broader coverage 22 × 22 × 19 cm 3 . Temporal resolution was 5 s for both protocols. Time-resolved images and blood–brain barrier permeability maps were qualitatively evaluated by two radiologists. Results: The experimental DCE-MRI scans showed no loss of qualitative information in any of the cases, while achieving substantially higher spatial resolution and whole-brain spatial coverage. Average qualitative scores (from 0 to 3) were 2.1 for the experimental scans and 1.1 for the conventional clinical scans. Conclusions: The proposed DCE-MRI approach provides clinically superior image quality with higher spatial resolution and coverage than currently available approaches. These advantages may allow comprehensive permeability mapping in the brain, which is especially valuable in the setting of large lesions or multiple lesions spread throughout the brain.

  5. Rapid whole brain myelin water content mapping without an external water standard at 1.5T.

    Science.gov (United States)

    Nguyen, Thanh D; Spincemaille, Pascal; Gauthier, Susan A; Wang, Yi

    2017-06-01

    The objective of this study is to develop rapid whole brain mapping of myelin water content (MWC) at 1.5T. The Fast Acquisition with Spiral Trajectory and T2prep (FAST-T2) pulse sequence originally developed for myelin water fraction (MWF) mapping was modified to obtain fast mapping of T1 and receiver coil sensitivity needed for MWC computation. The accuracy of the proposed T1 mapping was evaluated by comparing with the standard IR-FSE method. Numerical simulations were performed to assess the accuracy and reliability of the proposed MWC mapping. We also compared MWC values obtained with either cerebrospinal fluid (CSF) or an external water tube attached to the subject's head as the water reference. Our results from healthy volunteers show that whole brain MWC mapping is feasible in 7min and provides accurate brain T1 values. Regional brain WC and MWC measurements obtained with the internal CSF-based water standard showed excellent correlation (R>0.99) and negligible bias within narrow limits of agreement compared to those obtained with an external water standard. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 1H-MR spectroscopy of the rat hippocampus after whole brain irradiation: an in vivo study

    International Nuclear Information System (INIS)

    Ding Weijun; Yang Haihua; Wang Xufeng; Hu Wei; Lei Hao; Li Chunxia; Fang Fang; Fang Zhouxi

    2008-01-01

    Objective: To study the relationships between dynamic changes of the hippocampus metabolites, cognitive impairment and ultrastructural changes of hippocampus in rats during the initial 4 weeks after 6 MV X-ray whole-brain irradiation. Methods: 65 rats were randomly divided into foul groups as sham control (n=5), 10 Gy, 20 Gy and 30 Gy groups (n=20). The learning and memory ability was measured with the Y maze test 4, 8 weeks, 2, 6 months after irradiation. 1 H-MRS was performed after 2 or 4 weeks' brain irradiation. The ultrastructural changes of the hippocampus were observed by electronic microscope. Results: The learning and memorizing ability of irradiation groups was significantly different from that of control group. Compared with control group, the NAA/Ct and Cho/Cr ratio in the left hippocampus in 10 Gy, 20 Gy and 30 Gy groups at 2 weeks and 4 weeks decreased significantly. Neuronal mitochondria edema, endothelial cells swelling and lamina dissociation in myelin sheath were demonstrated in various degrees by electromicroscope at 4 weeks following whole brain irradiation. Conclusions: 1 H-MRS can be used to non-invasively monitor the metabolic changes, both quantitatively and dynamically, of the irradiated rat brain, 1 H-MRS is superior to MRI in detecting early abnormality of the brain. The NAA/Cr and Cho/Cr ratio in irradiated hippocampus could reflect the severity of the brain injury to some extent. (authors)

  7. Whole-brain functional magnetic resonance imaging of human brain during voluntary movements of dominant and subdominant hands

    International Nuclear Information System (INIS)

    Yu Wei; Yan Zixu; Ma Xiaohai; Zhang Zhaoqi; Lin Chongyu; Zang Yufeng; Weng Xuchu

    2003-01-01

    Objective: To identify the neural substrates of voluntary movements of dominant and subdominant hands by using the whole-brain functional magnetic resonance imaging. Methods: Seven right-handed healthy volunteers were scanned at a Sonata 1.5 Tesla magnetic resonance imaging scanner (Siemens) while they were performing the visually instructive movement tasks with their right and left index fingers. Image data were co-registered to correct head motion, spatially normalized according to the standard coordinates, and spatially smoothed with isotopic Guassian Kernel. Statistical parametric maps (activation maps) for right and left hands were generated respectively by cross-correlation analysis. Results: Voluntary movements of the right/dominant hand mainly activated contralateral primary motor cortex (MI), bilateral supplementary motor area (SMA), bilateral second motor area (MII), and ipsilateral cerebellum, whereas movements of the left/subdominant hand additionally elicited activation in contralateral premotor area (PMC). Moreover, activation volumes in SMA and MII during movements of the subdominant hand were significantly larger than those during movements of the dominant hand. Conclusion: A large set of structures in the cerebral cortex and cerebellum is involved in voluntary movements, as revealed by whole brain-based fMRI. Movements of the subdominant hand are more dependent on higher control areas, such as SMA and PMC, comparing to movements of the dominant hand

  8. Detection of whole-brain abnormalities in temporal lobe epilepsy using tensor-based morphometry with DARTEL

    Science.gov (United States)

    Li, Wenjing; He, Huiguang; Lu, Jingjing; Lv, Bin; Li, Meng; Jin, Zhengyu

    2009-10-01

    Tensor-based morphometry (TBM) is an automated technique for detecting the anatomical differences between populations by examining the gradients of the deformation fields used to nonlinearly warp MR images. The purpose of this study was to investigate the whole-brain volume changes between the patients with unilateral temporal lobe epilepsy (TLE) and the controls using TBM with DARTEL, which could achieve more accurate inter-subject registration of brain images. T1-weighted images were acquired from 21 left-TLE patients, 21 right-TLE patients and 21 healthy controls, which were matched in age and gender. The determinants of the gradient of deformation fields at voxel level were obtained to quantify the expansion or contraction for individual images relative to the template, and then logarithmical transformation was applied on it. A whole brain analysis was performed using general lineal model (GLM), and the multiple comparison was corrected by false discovery rate (FDR) with pleft-TLE patients, significant volume reductions were found in hippocampus, cingulate gyrus, precentral gyrus, right temporal lobe and cerebellum. These results potentially support the utility of TBM with DARTEL to study the structural changes between groups.

  9. Topological Alterations and Symptom-Relevant Modules in the Whole-Brain Structural Network in Semantic Dementia.

    Science.gov (United States)

    Ding, Junhua; Chen, Keliang; Zhang, Weibin; Li, Ming; Chen, Yan; Yang, Qing; Lv, Yingru; Guo, Qihao; Han, Zaizhu

    2017-01-01

    Semantic dementia (SD) is characterized by a selective decline in semantic processing. Although the neuropsychological pattern of this disease has been identified, its topological global alterations and symptom-relevant modules in the whole-brain anatomical network have not been fully elucidated. This study aims to explore the topological alteration of anatomical network in SD and reveal the modules associated with semantic deficits in this disease. We first constructed the whole-brain white-matter networks of 20 healthy controls and 19 patients with SD. Then, the network metrics of graph theory were compared between these two groups. Finally, we separated the network of SD patients into different modules and correlated the structural integrity of each module with the severity of the semantic deficits across patients. The network of the SD patients presented a significantly reduced global efficiency, indicating that the long-distance connections were damaged. The network was divided into the following four distinctive modules: the left temporal/occipital/parietal, frontal, right temporal/occipital, and frontal/parietal modules. The first two modules were associated with the semantic deficits of SD. These findings illustrate the skeleton of the neuroanatomical network of SD patients and highlight the key role of the left temporal/occipital/parietal module and the left frontal module in semantic processing.

  10. Connectomic markers of symptom severity in sport-related concussion: Whole-brain analysis of resting-state fMRI

    Directory of Open Access Journals (Sweden)

    Nathan W. Churchill

    Full Text Available Concussion is associated with significant adverse effects within the first week post-injury, including physical complaints and altered cognition, sleep and mood. It is currently unknown whether these subjective disturbances have reliable functional brain correlates. Resting-state functional magnetic resonance imaging (rs-fMRI has been used to measure functional connectivity of individuals after traumatic brain injury, but less is known about the relationship between functional connectivity and symptom assessments after a sport concussion. In this study, rs-fMRI was used to evaluate whole-brain functional connectivity for seventy (70 university-level athletes, including 35 with acute concussion and 35 healthy matched controls. Univariate analyses showed that greater symptom severity was mainly associated with lower pairwise connectivity in frontal, temporal and insular regions, along with higher connectivity in a sparser set of cerebellar regions. A novel multivariate approach also extracted two components that showed reliable covariation with symptom severity: (1 a network of frontal, temporal and insular regions where connectivity was negatively correlated with symptom severity (replicating the univariate findings; and (2 a network with anti-correlated elements of the default-mode network and sensorimotor system, where connectivity was positively correlated with symptom severity. These findings support the presence of connectomic signatures of symptom complaints following a sport-related concussion, including both increased and decreased functional connectivity within distinct functional brain networks. Keywords: fMRI, Functional connectivity, Concussion, Brain injury, Symptoms

  11. Connectomic markers of symptom severity in sport-related concussion: Whole-brain analysis of resting-state fMRI.

    Science.gov (United States)

    Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

    2018-01-01

    Concussion is associated with significant adverse effects within the first week post-injury, including physical complaints and altered cognition, sleep and mood. It is currently unknown whether these subjective disturbances have reliable functional brain correlates. Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to measure functional connectivity of individuals after traumatic brain injury, but less is known about the relationship between functional connectivity and symptom assessments after a sport concussion. In this study, rs-fMRI was used to evaluate whole-brain functional connectivity for seventy (70) university-level athletes, including 35 with acute concussion and 35 healthy matched controls. Univariate analyses showed that greater symptom severity was mainly associated with lower pairwise connectivity in frontal, temporal and insular regions, along with higher connectivity in a sparser set of cerebellar regions. A novel multivariate approach also extracted two components that showed reliable covariation with symptom severity: (1) a network of frontal, temporal and insular regions where connectivity was negatively correlated with symptom severity (replicating the univariate findings); and (2) a network with anti-correlated elements of the default-mode network and sensorimotor system, where connectivity was positively correlated with symptom severity. These findings support the presence of connectomic signatures of symptom complaints following a sport-related concussion, including both increased and decreased functional connectivity within distinct functional brain networks.

  12. Voxel-based comparison of whole brain gray matter of patients with mild Alzheimer's disease with normal aging volunteers

    International Nuclear Information System (INIS)

    Xie Sheng; Wu Hongkun; Xiao Jiangxi; Wang Yinhua; Jiang Xuexiang

    2006-01-01

    Objective: To detect gray matter abnormalities of whole brain in patients with mild Alzheimer's disease (AD) by voxel-based morphometry (VBM). Methods: Thirteen patients with mild Alzheimer's disease and sixteen normal aging volunteers underwent 3D SPGR scanning. For every subject, data was transferred to PC to be normalized, segmented and smoothed using SPM99. Non-dependent samples T-tests were conducted to compare gray matter' density voxel to voxel between the two groups. Results Significant reductions in gray matter density were found in the bilateral hippocampi and nucleus amygdalae, bilateral insulae, bilateral medial thalami, bilateral rectus gyri, right superior temporal gyms, right caudate nucleus, fight prefrontal lobe, right basal forebrain and portions of right occipital lobe. Conclusion: VBM reveals significant gray matter' reductions of numeral cortices in mild Alzheimer's disease. It can be a useful method to evaluate the anatomical changes in the progress of the disease. (authors)

  13. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  14. Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T.

    Science.gov (United States)

    Hagberg, G E; Bause, J; Ethofer, T; Ehses, P; Dresler, T; Herbert, C; Pohmann, R; Shajan, G; Fallgatter, A; Pavlova, M A; Scheffler, K

    2017-01-01

    Mapping of the longitudinal relaxation time (T 1 ) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T 1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T 2 -dependent variation of the adiabatic inversion efficiency were investigated by single slice T 1 mapping with inversion recovery EPI measurements, quantitative T 2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T 1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T 1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T 1 estimates at high field, the proposed correction methods resulted in an improved precision, with test-retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Treatment planning and 3D dose verification of whole brain radiation therapy with hippocampal avoidance in rats

    International Nuclear Information System (INIS)

    Yoon, S W; Miles, D; Reinsvold, M; Kirsch, D; Oldham, M; Cramer, C

    2017-01-01

    Despite increasing use of stereotactic radiosurgery, whole brain radiotherapy (WBRT) continues to have a therapeutic role in a selected subset of patients. Selectively avoiding the hippocampus during such treatment (HA-WBRT) emerged as a strategy to reduce the cognitive morbidity associated with WBRT and gave rise to a recently published the phase II trial (RTOG 0933) and now multiple ongoing clinical trials. While conceptually hippocampal avoidance is supported by pre-clinical evidence showing that the hippocampus plays a vital role in memory, there is minimal pre-clinic data showing that selectively avoiding the hippocampus will reduce radiation-induced cognitive decline. Largely the lack of pre-clinical evidence can be attributed to the technical hurdles associated with delivering precise conformal treatment the rat brain. In this work we develop a novel conformal HA-WBRT technique for Wistar rats, utilizing a 225kVp micro-irradiator with precise 3D-printed radiation blocks designed to spare hippocampus while delivering whole brain dose. The technique was verified on rodent-morphic Presage ® 3D dosimeters created from micro-CT scans of Wistar rats with Duke Large Field-of-View Optical Scanner (DLOS) at 1mm isotropic voxel resolution. A 4-field box with parallel opposed AP-PA and two lateral opposed fields was explored with conformal hippocampal sparing aided by 3D-printed radiation blocks. The measured DVH aligned reasonably well with that calculated from SmART Plan Monte Carlo simulations with simulated blocks for 4-field HA-WBRT with both demonstrating hippocampal sparing of 20% volume receiving less than 30% the prescription dose. (paper)

  16. Visualizing whole-brain DTI tractography with GPU-based Tuboids and LoD management.

    Science.gov (United States)

    Petrovic, Vid; Fallon, James; Kuester, Falko

    2007-01-01

    Diffusion Tensor Imaging (DTI) of the human brain, coupled with tractography techniques, enable the extraction of large-collections of three-dimensional tract pathways per subject. These pathways and pathway bundles represent the connectivity between different brain regions and are critical for the understanding of brain related diseases. A flexible and efficient GPU-based rendering technique for DTI tractography data is presented that addresses common performance bottlenecks and image-quality issues, allowing interactive render rates to be achieved on commodity hardware. An occlusion query-based pathway LoD management system for streamlines/streamtubes/tuboids is introduced that optimizes input geometry, vertex processing, and fragment processing loads, and helps reduce overdraw. The tuboid, a fully-shaded streamtube impostor constructed entirely on the GPU from streamline vertices, is also introduced. Unlike full streamtubes and other impostor constructs, tuboids require little to no preprocessing or extra space over the original streamline data. The supported fragment processing levels of detail range from texture-based draft shading to full raycast normal computation, Phong shading, environment mapping, and curvature-correct text labeling. The presented text labeling technique for tuboids provides adaptive, aesthetically pleasing labels that appear attached to the surface of the tubes. Furthermore, an occlusion query aggregating and scheduling scheme for tuboids is described that reduces the query overhead. Results for a tractography dataset are presented, and demonstrate that LoD-managed tuboids offer benefits over traditional streamtubes both in performance and appearance.

  17. Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

    2017-09-15

    To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

  18. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases : Research protocol CAR-study B

    NARCIS (Netherlands)

    Schimmel, W.C.M.; Verhaak, E.; Hanssens, Patrick E. J.; Gehring, K.; Sitskoorn, M.M.

    2018-01-01

    Background Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is

  19. Experimental Study Comparing a Traditional Approach to Performance Appraisal Training to a Whole-Brain Training Method at C.B. Fleet Laboratories

    Science.gov (United States)

    Selden, Sally; Sherrier, Tom; Wooters, Robert

    2012-01-01

    The purpose of this study is to examine the effects of a new approach to performance appraisal training. Motivated by split-brain theory and existing studies of cognitive information processing and performance appraisals, this exploratory study examined the effects of a whole-brain approach to training managers for implementing performance…

  20. A functional genomics screen in planarians reveals regulators of whole-brain regeneration

    Science.gov (United States)

    Roberts-Galbraith, Rachel H; Brubacher, John L; Newmark, Phillip A

    2016-01-01

    Planarians regenerate all body parts after injury, including the central nervous system (CNS). We capitalized on this distinctive trait and completed a gene expression-guided functional screen to identify factors that regulate diverse aspects of neural regeneration in Schmidtea mediterranea. Our screen revealed molecules that influence neural cell fates, support the formation of a major connective hub, and promote reestablishment of chemosensory behavior. We also identified genes that encode signaling molecules with roles in head regeneration, including some that are produced in a previously uncharacterized parenchymal population of cells. Finally, we explored genes downregulated during planarian regeneration and characterized, for the first time, glial cells in the planarian CNS that respond to injury by repressing several transcripts. Collectively, our studies revealed diverse molecules and cell types that underlie an animal’s ability to regenerate its brain. DOI: http://dx.doi.org/10.7554/eLife.17002.001 PMID:27612384

  1. Improved plan quality with automated radiotherapy planning for whole brain with hippocampus sparing: a comparison to the RTOG 0933 trial.

    Science.gov (United States)

    Krayenbuehl, J; Di Martino, M; Guckenberger, M; Andratschke, N

    2017-10-02

    Whole-brain radiation therapy (WBRT) with hippocampus sparing (HS) has been investigated by the radiation oncology working group (RTOG) 0933 trial for patients with multiple brain metastases. They showed a decrease of adverse neurocognitive effects with HS WBRT compared to WBRT alone. With the development of automated treatment planning system (aTPS) in the last years, a standardization of the plan quality at a high level was achieved. The goal of this study was to evaluate the feasibility of using an aTPS for the treatment of HS WBRT and see if the RTOG 0933 dose constraints could be achieved and improved. Ten consecutive patients treated with HS WBRT were enrolled in this study. 10 × 3 Gy was prescribed according to the RTOG 0933 protocol to 92% of the target volume (whole-brain excluding the hippocampus expanded by 5 mm in 3-dimensions). In contrast to RTOG 0933, the maximum allowed point dose to normal brain was significantly lowered and restricted to 36.5 Gy. All patients were planned with volumetric modulated arc therapy (VMAT) technique using four arcs. Plans were optimized using Auto-Planning (AP) (Philips Radiation Oncology Systems) with one single AP template and optimization. All the constraints from the RTOG 0933 trial were achieved. A significant improvement for the maximal dose to 2% of the brain with a reduction of 4 Gy was achieved (33.5 Gy vs. RTOG 37.5 Gy) and the minimum hippocampus dose was reduced by 10% (8.1 Gy vs. RTOG 9 Gy). A steep dose gradient around the hippocampus was achieved with a mean dose of 27.3 Gy at a distance between 0.5 cm and 1 cm from the hippocampus. The effective working time to optimize a plan was kept below 6'. Automated treatment planning for HS WBRT was able to fulfil all the recommendations from the RTOG 0933 study while significantly improving dose homogeneity and decreasing unnecessary hot spot in the normal brain. With this approach, a standardization of plan quality was achieved and the effective

  2. Evaluation of usability of the shielding effect for thyroid shield for peripheral dose during whole brain radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Myung Sic; Park, Ju Kyeong; Lee, Seung Hun; Kim, Yang Su; Lee, Sun Young; Cha, Seok Yong [Dept. of Radiation Oncology, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-12-15

    To reduce the radiation dose to the thyroid that is affected to scattered radiation, the shield was used. And we evaluated the shielding effect for the thyroid during whole brain radiation therapy. To measure the dose of the thyroid, 300cGy were delivered to the phantom using a linear accelerator(Clinac iX VARIAN, USA.)in the way of the 6MV X-ray in bilateral. To measure the entrance surface dose of the thyroid, five glass dosimeters were placed in the 10th slice's surface of the phantom with a 1.5 cm interval. The average values were calculated by measured values in five times each, using bismuth shield, 0.5 mmPb shield, self-made 1.0 mmPb shield and unshield. In the same location, to measure the depth dose of the thyroid, five glass dosimeters were placed in the 10th slice by 2.5 cm depth of the phantom with a 1.5 cm interval. The average values were calculated by measured values in five times each, using bismuth shield, 0.5 mmPb shield, self-made 1.0 mmPb shield and unshield. Entrance surface dose of the thyroid were respectively 44.89 mGy at the unshield, 36.03 mGy at the bismuth shield, 31.03 mGy at the 0.5 mmPb shield and 23.21 mGy at a self-made 1.0 mmPb shield. In addition, the depth dose of the thyroid were respectively 36.10 mGy at the unshield, 34.52 mGy at the bismuth shield, 32.28 mGy at the 0.5 mmPb shield and 25.50 mGy at a self-made 1.0 mmPb shield. The thyroid was affected by the secondary scattering dose and leakage dose outside of the radiation field during whole brain radiation therapy. When using a shield in the thyroid, the depth dose of thyroid showed 11-30% reduction effect and the surface dose of thyroid showed 20-48% reduction effect. Therefore, by using the thyroid shield, it is considered to effectively protect the thyroid and can perform the treatment.

  3. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  4. Three-dimensional true FISP for high-resolution imaging of the whole brain

    International Nuclear Information System (INIS)

    Schmitz, B.; Hagen, T.; Reith, W.

    2003-01-01

    While high-resolution T1-weighted sequences, such as three-dimensional magnetization-prepared rapid gradient-echo imaging, are widely available, there is a lack of an equivalent fast high-resolution sequence providing T2 contrast. Using fast high-performance gradient systems we show the feasibility of three-dimensional true fast imaging with steady-state precession (FISP) to fill this gap. We applied a three-dimensional true-FISP protocol with voxel sizes down to 0.5 x 0.5 x 0.5 mm and acquisition times of approximately 8 min on a 1.5-T Sonata (Siemens, Erlangen, Germany) magnetic resonance scanner. The sequence was included into routine brain imaging protocols for patients with cerebrospinal-fluid-related intracranial pathology. Images from 20 patients and 20 healthy volunteers were evaluated by two neuroradiologists with respect to diagnostic image quality and artifacts. All true-FISP scans showed excellent imaging quality free of artifacts in patients and volunteers. They were valuable for the assessment of anatomical and pathologic aspects of the included patients. High-resolution true-FISP imaging is a valuable adjunct for the exploration and neuronavigation of intracranial pathologies especially if cerebrospinal fluid is involved. (orig.)

  5. Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs.

    Science.gov (United States)

    Demuru, M; Gouw, A A; Hillebrand, A; Stam, C J; van Dijk, B W; Scheltens, P; Tijms, B M; Konijnenberg, E; Ten Kate, M; den Braber, A; Smit, D J A; Boomsma, D I; Visser, P J

    2017-08-29

    Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.

  6. Medical Image Processing for Fully Integrated Subject Specific Whole Brain Mesh Generation

    Directory of Open Access Journals (Sweden)

    Chih-Yang Hsu

    2015-05-01

    Full Text Available Currently, anatomically consistent segmentation of vascular trees acquired with magnetic resonance imaging requires the use of multiple image processing steps, which, in turn, depend on manual intervention. In effect, segmentation of vascular trees from medical images is time consuming and error prone due to the tortuous geometry and weak signal in small blood vessels. To overcome errors and accelerate the image processing time, we introduce an automatic image processing pipeline for constructing subject specific computational meshes for entire cerebral vasculature, including segmentation of ancillary structures; the grey and white matter, cerebrospinal fluid space, skull, and scalp. To demonstrate the validity of the new pipeline, we segmented the entire intracranial compartment with special attention of the angioarchitecture from magnetic resonance imaging acquired for two healthy volunteers. The raw images were processed through our pipeline for automatic segmentation and mesh generation. Due to partial volume effect and finite resolution, the computational meshes intersect with each other at respective interfaces. To eliminate anatomically inconsistent overlap, we utilized morphological operations to separate the structures with a physiologically sound gap spaces. The resulting meshes exhibit anatomically correct spatial extent and relative positions without intersections. For validation, we computed critical biometrics of the angioarchitecture, the cortical surfaces, ventricular system, and cerebrospinal fluid (CSF spaces and compared against literature values. Volumina and surface areas of the computational mesh were found to be in physiological ranges. In conclusion, we present an automatic image processing pipeline to automate the segmentation of the main intracranial compartments including a subject-specific vascular trees. These computational meshes can be used in 3D immersive visualization for diagnosis, surgery planning with haptics

  7. Hair-sparing whole brain radiotherapy with volumetric arc therapy in patients treated for brain metastases: dosimetric and clinical results of a phase II trial

    International Nuclear Information System (INIS)

    De Puysseleyr, Annemieke; Ost, Piet; Van De Velde, Joris; Speleers, Bruno; Vercauteren, Tom; Goedgebeur, Anneleen; Van Hoof, Tom; Boterberg, Tom; De Neve, Wilfried; De Wagter, Carlos

    2014-01-01

    To report the dosimetric results and impact of volumetric arc therapy (VMAT) on temporary alopecia and hair-loss related quality of life (QOL) in whole brain radiotherapy (WBRT). The potential of VMAT-WBRT to reduce the dose to the hair follicles was assessed. A human cadaver was treated with both VMAT-WBRT and conventional opposed field (OF) WBRT, while the subcutaneously absorbed dose was measured by radiochromic films and calculated by the planning system. The impact of these dose reductions on temporary alopecia was examined in a prospective phase II trial, with the mean score of hair loss at 1 month after VMAT-WBRT (EORTC-QOL BN20) as a primary endpoint and delivering a dose of 20 Gy in 5 fractions. An interim analysis was planned after including 10 patients to rule out futility, defined as a mean score of hair loss exceeding 56.7. A secondary endpoint was the global alopecia areata severity score measured with the “Severity of Alopecia Tool” (SALT) with a scale of 0 (no hair loss) to 100 (complete alopecia). For VMAT-WBRT, the cadaver measurements demonstrated a dose reduction to the hair follicle volume of 20.5% on average and of 41.8% on the frontal-vertex-occipital medial axis as compared to OF-WBRT. In the phase II trial, a total of 10 patients were included before the trial was halted due to futility. The EORTC BN20 hair loss score following WBRT was 95 (SD 12.6). The average median dose to the hair follicle volume was 12.6 Gy (SD 0.9), corresponding to a 37% dose reduction compared to the prescribed dose. This resulted in a mean SALT-score of 75. Compared to OF-WBRT, VMAT-WBRT substantially reduces hair follicle dose. These dose reductions could not be related to an improved QOL or SALT score

  8. A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases: research protocol CAR-study B.

    Science.gov (United States)

    Schimmel, Wietske C M; Verhaak, Eline; Hanssens, Patrick E J; Gehring, Karin; Sitskoorn, Margriet M

    2018-02-21

    Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups. The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717

  9. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

    Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

  10. A case of lung adenocarcinoma with multiple intracranial hemorrhages of brain metastases after whole-brain radiation therapy

    International Nuclear Information System (INIS)

    Nakamichi, Shinji; Hirano, Satoshi; Asao, Tetsuhiko; Takeda, Yuichiro; Sugiyama, Haruhito; Kobayashi, Nobuyuki

    2011-01-01

    Whole-brain radiation therapy (WBRT) is widely applied in cases of brain metastases of non-small cell lung cancer (NSCLC). However, there are few case reports on hemorrhages of brain metastases occurring after WBRT. A 63-year-old woman was given a diagnosis of stage IV (T4N0M1b) lung adenocarcinoma about 4 years previously, and received chemotherapy regimens and gamma knife radiosurgery. However, her brain metastases exacerbated and she received WBRT in November 2010 and docetaxel monotherapy in December 2010. Two weeks after completing WBRT, she experienced dysarthria and an MRI showed multiple hemorrhages within brain metastases. Over a period of careful observation, these hemorrhages repeatedly alternated between improvement and exacerbation. Radiotherapy for metastatic brain tumors is considered to suppress hemorrhagic events of brain metastases. However, multiple intracranial hemorrhages of brain metastases occurred after WBRT in the present case. The accumulation of further studies of similar cases is necessary to identify the exact mechanism of these hemorrhages. (author)

  11. Potential risk for healthy siblings to develop schizophrenia: evidence from pattern classification with whole-brain connectivity.

    Science.gov (United States)

    Liu, Meijie; Zeng, Ling-Li; Shen, Hui; Liu, Zhening; Hu, Dewen

    2012-03-28

    Recent resting-state functional connectivity MRI studies using group-level statistical analysis have demonstrated the inheritable characters of schizophrenia. The objective of the present study was to use pattern classification as a means to investigate schizophrenia inheritance based on the whole-brain resting-state functional connectivity at the individual subject level. One-against-one pattern classifications were made amongst three groups (i.e. patients diagnosed with schizophrenia, healthy siblings, and healthy controls after preprocessing), resulting in an 80.4% separation between patients with schizophrenia and healthy controls, a 77.6% separation between schizophrenia patients and their healthy siblings, and a 78.7% separation between healthy siblings and healthy controls, respectively. These results suggest that the healthy siblings of schizophrenia patients have an altered resting-state functional connectivity pattern compared with healthy controls. Thus, healthy siblings may have a potential higher risk for developing schizophrenia compared with the general population. Moreover, this pattern differed from that of schizophrenia patients and may contribute to the normal behavior exhibition of healthy siblings in daily life.

  12. Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

    International Nuclear Information System (INIS)

    Gondi, Vinai; Tome, Wolfgang A.; Marsh, James; Struck, Aaron; Ghia, Amol; Turian, Julius V.; Bentzen, Soren M.; Kuo, John S.; Khuntia, Deepak; Mehta, Minesh P.

    2010-01-01

    Background and purpose: RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin). Materials/methods: Patients with ≤10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p 3 increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis. Conclusion: With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.

  13. Comparison of NREM sleep and intravenous sedation through local information processing and whole brain network to explore the mechanism of general anesthesia.

    Science.gov (United States)

    Li, Yun; Wang, Shengpei; Pan, Chuxiong; Xue, Fushan; Xian, Junfang; Huang, Yaqi; Wang, Xiaoyi; Li, Tianzuo; He, Huiguang

    2018-01-01

    The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. Institutional Review Board (IRB) ChiCTR-IOC-15007454.

  14. Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases

    Directory of Open Access Journals (Sweden)

    Daniel eGorovets

    2015-05-01

    Full Text Available Purpose: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT in patients with brain metastases treated with stereotactic radiosurgery (SRS as their initial radiotherapy approach. Material and Methods: Patients with brain metastases treated with SRS from 2001-2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky Performance Status ≥70, and life expectancy ≥3 mo. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-yr WBRT-free survival (N=104, and those who died or required salvage WBRT within 3 mo of SRS (N=56. Differences between these groups were assessed by univariate and multivariate analyses.Results: Median survival for all patients was 11 mo. Among patients with ≥1-yr WBRT-free survival, median survival was 33 mo [12-107 mo] with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p<0.05 included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions. After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival.Conclusions: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.

  15. Aberrant Functional Connectivity Architecture in Participants with Chronic Insomnia Disorder Accompanying Cognitive Dysfunction: A Whole-Brain, Data-Driven Analysis

    Directory of Open Access Journals (Sweden)

    Ran Pang

    2017-05-01

    Full Text Available Objectives: Although it is widely observed that chronic insomnia disorder (CID is associated with cognitive impairment, the neurobiological mechanisms underlying this remain unclear. Prior neuroimaging studies have confirmed that a close correlation exists between functional connectivity and cognitive impairment. Based on this observation, in this study we used resting-state functional magnetic resonance imaging (rs-fMRI to study the relationship between whole brain functional connectivity and cognitive function in CID.Methods: We included 39 patients with CID and 28 age-, gender-, and education-matched healthy controls (HC. Abnormalities in functional connectivity were identified by comparing the correlation coefficients for each pair of 116 brain regions between CID and HC.Results: Cognitive impairment was associated with reduced subjective insomnia scores after controlling for age, gender, and educational effects. Compared with HC, patients with CID had larger negative correlations within the task-negative network [medial prefrontal cortex (mPFC, precuneus, inferior temporal gyrus, cerebellum, and superior parietal gyrus], and between two intrinsic anti-correlation networks (mPFC and middle temporal gyrus; supplementary motor area and cerebellum. Patients with CID also had decreased positive correlations within the default mode network (DMN, and between the cerebellum and DMN, which mainly comprises the mPFC and posterior cingulated cortex. There were positive correlations of decreased positive connectivity with subjective sleep scores and MMSE scores, and increased negative correlations between the task-negative-network and MMSE scores in CID.Conclusions: Using rs-fMRI, our results support previous observations of cortical disconnection in CID in the prefrontal and DMN networks. Moreover, abnormal correlations within the task-negative network, and between two intrinsically anti-correlation networks, might be important neurobiological

  16. The role of stereotactic radiation therapy and whole-brain radiotherapy in the treatment of multiple brain metastases

    International Nuclear Information System (INIS)

    Chen Xiujun; Xiao Jianping; Li Xiangpan; Jiang Xuesong; Zhang Ye; Xu Yingjie; Dai Jianrong; Li Yexiong

    2012-01-01

    Objective: To summarize the results of stereotactic radiation therapy (SRT) with or without whole-brain radiotherapy (WBRT) in the treatment of multiple brain metastasis. Methods: From May 1995 to April 2010, totally 98 newly diagnosed multiple (2 - 13 lesions) brain metastases patients were treated in our centre. Forty-four patients were treated with SRT alone and 54 with SRT + WBRT. Dose fractionation schemes were 15 -26 Gy in 1 fraction or 24.0 -52.5 Gy in 2 - 15 fractions with 3.5 - 12.0 Gy per fraction, depending on the tumor volume, location, and history of prior irradiation. Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis. The median age of the whole group was 55 years. The survival time was calculated from the date of radiation treatment to the day of death by any cause. Results: The median follow-up time for the whole group was 12 months, and the follow-up rate was 100%. The median overall survival time was 13.5 months for the whole group, there was no difference between SRT alone group and SRT + WBRT group (13.0 months vs. 13.5 months, χ 2 =0.31, P =0.578). The Karnofsky Performance Score (KPS) at the time of treatment (χ 2 =6.25, P =0.012), the interval between the diagnosis of the primary tumor and brain metastases (χ 2 =7.34, P =0.025) and the status of extracranial metastases (χ 2 =4.20, P =0.040) were independent prognosis factors for survival in multivariate analyses. Conclusions: Stereotactic radiation therapy is an effective and alternative treatment choice for multiple brain metastases. (authors)

  17. Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

    Energy Technology Data Exchange (ETDEWEB)

    Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya; Von Eyben, Rie; Gibbs, Iris C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Choi, Clara Y.H. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Department of Radiation Oncology, Santa Clara Valley Medical Center, San Jose, California (United States); Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Adler, John R. [Department of Neurosurgery, Stanford University School of Medicine, Stanford, California (United States); Hancock, Steven L. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Soltys, Scott G., E-mail: sgsoltys@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-08-01

    Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  18. Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

    International Nuclear Information System (INIS)

    Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Rhodes, C. Harker; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

    2013-01-01

    Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

  19. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  20. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  1. Neurocognitive Function of Patients with Brain Metastasis Who Received Either Whole Brain Radiotherapy Plus Stereotactic Radiosurgery or Radiosurgery Alone

    International Nuclear Information System (INIS)

    Aoyama, Hidefumi; Tago, Masao; Kato, Norio; Toyoda, Tatsuya; Kenjyo, Masahiro; Hirota, Saeko; Shioura, Hiroki; Inomata, Taisuke; Kunieda, Etsuo; Hayakawa, Kazushige; Nakagawa, Keiichi; Kobashi, Gen; Shirato, Hiroki

    2007-01-01

    Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. Results: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of ≤27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of ≥3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of ≥27 or whose baseline MMSE score was ≤26 but had improved to ≥27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). Conclusion: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible

  2. Time efficient whole-brain coverage with MR Fingerprinting using slice-interleaved echo-planar-imaging.

    Science.gov (United States)

    Rieger, Benedikt; Akçakaya, Mehmet; Pariente, José C; Llufriu, Sara; Martinez-Heras, Eloy; Weingärtner, Sebastian; Schad, Lothar R

    2018-04-27

    Magnetic resonance fingerprinting (MRF) is a promising method for fast simultaneous quantification of multiple tissue parameters. The objective of this study is to improve the coverage of MRF based on echo-planar imaging (MRF-EPI) by using a slice-interleaved acquisition scheme. For this, the MRF-EPI is modified to acquire several slices in a randomized interleaved manner, increasing the effective repetition time of the spoiled gradient echo readout acquisition in each slice. Per-slice matching of the signal-trace to a precomputed dictionary allows the generation of T 1 and T 2 * maps with integrated B 1 + correction. Subsequent compensation for the coil sensitivity profile and normalization to the cerebrospinal fluid additionally allows for quantitative proton density (PD) mapping. Numerical simulations are performed to optimize the number of interleaved slices. Quantification accuracy is validated in phantom scans and feasibility is demonstrated in-vivo. Numerical simulations suggest the acquisition of four slices as a trade-off between quantification precision and scan-time. Phantom results indicate good agreement with reference measurements (Difference T 1 : -2.4 ± 1.1%, T 2 *: -0.5 ± 2.5%, PD: -0.5 ± 7.2%). In-vivo whole-brain coverage of T 1 , T 2 * and PD with 32 slices was acquired within 3:36 minutes, resulting in parameter maps of high visual quality and comparable performance with single-slice MRF-EPI at 4-fold scan-time reduction.

  3. A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

    Science.gov (United States)

    Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

    2014-01-01

    Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

  4. Cost-effectiveness Analysis of Stereotactic Radiosurgery Alone Versus Stereotactic Radiosurgery with Upfront Whole Brain Radiation Therapy for Brain Metastases.

    Science.gov (United States)

    Kim, H; Rajagopalan, M S; Beriwal, S; Smith, K J

    2017-10-01

    Stereotactic radiosurgery (SRS) alone or upfront whole brain radiation therapy (WBRT) plus SRS are the most commonly used treatment options for one to three brain oligometastases. The most recent randomised clinical trial result comparing SRS alone with upfront WBRT plus SRS (NCCTG N0574) has favoured SRS alone for neurocognitive function, whereas treatment options remain controversial in terms of cognitive decline and local control. The aim of this study was to conduct a cost-effectiveness analysis of these two competing treatments. A Markov model was constructed for patients treated with SRS alone or SRS plus upfront WBRT based on largely randomised clinical trials. Costs were based on 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) and effectiveness was measured in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were carried out. Strategies were evaluated from the healthcare payer's perspective with a willingness-to-pay threshold of $100 000 per QALY gained. In the base case analysis, the median survival was 9 months for both arms. SRS alone resulted in an ICER of $9917 per QALY gained. In one-way sensitivity analyses, results were most sensitive to variation in cognitive decline rates for both groups and median survival rates, but the SRS alone remained cost-effective for most parameter ranges. Based on the current available evidence, SRS alone was found to be cost-effective for patients with one to three brain metastases compared with upfront WBRT plus SRS. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  5. Accelerated whole brain intracranial vessel wall imaging using black blood fast spin echo with compressed sensing (CS-SPACE).

    Science.gov (United States)

    Zhu, Chengcheng; Tian, Bing; Chen, Luguang; Eisenmenger, Laura; Raithel, Esther; Forman, Christoph; Ahn, Sinyeob; Laub, Gerhard; Liu, Qi; Lu, Jianping; Liu, Jing; Hess, Christopher; Saloner, David

    2018-06-01

    Develop and optimize an accelerated, high-resolution (0.5 mm isotropic) 3D black blood MRI technique to reduce scan time for whole-brain intracranial vessel wall imaging. A 3D accelerated T 1 -weighted fast-spin-echo prototype sequence using compressed sensing (CS-SPACE) was developed at 3T. Both the acquisition [echo train length (ETL), under-sampling factor] and reconstruction parameters (regularization parameter, number of iterations) were first optimized in 5 healthy volunteers. Ten patients with a variety of intracranial vascular disease presentations (aneurysm, atherosclerosis, dissection, vasculitis) were imaged with SPACE and optimized CS-SPACE, pre and post Gd contrast. Lumen/wall area, wall-to-lumen contrast ratio (CR), enhancement ratio (ER), sharpness, and qualitative scores (1-4) by two radiologists were recorded. The optimized CS-SPACE protocol has ETL 60, 20% k-space under-sampling, 0.002 regularization factor with 20 iterations. In patient studies, CS-SPACE and conventional SPACE had comparable image scores both pre- (3.35 ± 0.85 vs. 3.54 ± 0.65, p = 0.13) and post-contrast (3.72 ± 0.58 vs. 3.53 ± 0.57, p = 0.15), but the CS-SPACE acquisition was 37% faster (6:48 vs. 10:50). CS-SPACE agreed with SPACE for lumen/wall area, ER measurements and sharpness, but marginally reduced the CR. In the evaluation of intracranial vascular disease, CS-SPACE provides a substantial reduction in scan time compared to conventional T 1 -weighted SPACE while maintaining good image quality.

  6. CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

    International Nuclear Information System (INIS)

    Laack, Nadia N.; O'Neill, Brian Patrick; Ballman, Karla V.; O'Fallon, Judith Rich; Carrero, Xiomara W.; Kurtin, Paul J.; Scheithauer, Bernd W.; Brown, Paul D.; Habermann, Thomas M.; Colgan, Joseph P.; Gilbert, Mark R.; Hawkins, Roland B.; Morton, Roscoe F.; Windschitl, Harry E.; Fitch, Tom R.; Pajon, Eduardo R.

    2011-01-01

    Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

  7. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia.

    Directory of Open Access Journals (Sweden)

    Junie P Warrington

    Full Text Available Whole brain radiation therapy (WBRT is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40-50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia or 21% oxygen (normoxia for 28 days, initiated 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.

  8. Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

    International Nuclear Information System (INIS)

    Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

    2017-01-01

    Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

  9. Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

    2017-02-01

    Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

  10. Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Sundaresan, P.; Yeghiaian, R.; Gebski, V.

    2010-01-01

    Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

  11. Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers.

    Science.gov (United States)

    Stening, Eva; Persson, Jonas; Eriksson, Elias; Wahlund, Lars-Olof; Zetterberg, Henrik; Söderlund, Hedvig

    2017-05-30

    Apolipoprotein E (APOE) ε4 has been associated with smaller hippocampal volumes in healthy aging, while findings in young adults are inconclusive. Previous studies have mostly used univariate methods, and without considering potential anterior/posterior differences. Here, we used a multivariate method, partial least squares, and assessed whole-brain structural covariance of the anterior (aHC) and posterior (pHC) hippocampus in young adults (n=97) as a function of APOE ε4 status and sex. Two significant patterns emerged: (1) specific structural covariance of the aHC with frontal regions, temporal and occipital areas in APOE ε4 women, whereas the volume of both the aHC and pHC in all other groups co-varied with frontal, parietal and cerebellar areas; and (2) opposite structural covariance of the pHC in ε4 carriers compared to the aHC in non-carriers, with the pHC of ε4 carriers covarying with parietal and frontal areas, and the aHC of ε4 non-carriers covarying with motor areas and the middle frontal gyrus. APOE ε4 has in young adults been associated with better episodic and spatial memory, functions involving the aHC and pHC, respectively. We found no associations between structural covariance and performance, suggesting that other factors underlie the performance differences seen between carriers and non-carriers. Our findings indicate that APOE ε4 carriers and non-carriers differ in hippocampal organization and that there are differences as a function of sex and hippocampal segment. They stress the need to consider the hippocampus as a heterogeneous structure, and highlight the benefits of multivariate methods in assessing group differences in the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: a dosimetric study using helical tomotherapy

    International Nuclear Information System (INIS)

    Marsh, J.C.; Gielda, B.T.; Herskovic, A.M.; Turian, J.V.

    2010-01-01

    Full text: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with VlOO ∼ 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V 100. Results: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/ 14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean VlOO for the rest of the brain (PTV) were 94.7% (PCl) and 95.1 % (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). Conclusions: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.

  13. Comparison of volumetric modulated arc therapy and intensity modulated radiation therapy for whole brain hippocampal sparing treatment plans based on radiobiological modeling

    Directory of Open Access Journals (Sweden)

    Ethan Kendall

    2018-01-01

    Full Text Available Introduction: In this article, we report the results of our investigation on comparison of radiobiological aspects of treatment plans with linear accelerator-based intensity-modulated radiation therapy and volumetric-modulated arc therapy for patients having hippocampal avoidance whole-brain radiation therapy. Materials and Methods: In this retrospective study using the dose-volume histogram, we calculated and compared biophysical indices of equivalent uniform dose, tumor control probability, and normal tissue complication probability (NTCP for 15 whole-brain radiotherapy patients. Results and Discussions: Dose-response models for tumors and critical structures were separated into two groups: mechanistic and empirical. Mechanistic models formulate mathematically with describable relationships while empirical models fit data through empirical observations to appropriately determine parameters giving results agreeable to those given by mechanistic models. Conclusions: Techniques applied in this manuscript could be applied to any other organs or types of cancer to evaluate treatment plans based on radiobiological modeling.

  14. Whole brain CT perfusion deficits using 320-detector-row CT scanner in TIA patients are associated with ABCD2 score.

    Science.gov (United States)

    Mehta, Bijal K; Mustafa, Ghulam; McMurtray, Aaron; Masud, Mohammed W; Gunukula, Sameer K; Kamal, Haris; Kandel, Amit; Beltagy, Abdelrahman; Li, Ping

    2014-01-01

    Transient ischemic attacks (TIA) are cerebral ischemic events without infarction. The uses of CT perfusion (CTP) techniques such as cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and cerebral blood flow (CBF) provide real time data about ischemia. It has been shown that CTP changes occur in less sensitive CTP scanners in patients with TIA. Larger detector row CTP (whole brain perfusion studies) may show that CTP abnormalities are more prevalent than previously noted. It is also unclear if these changes are associated with TIA severity. To demonstrate that TIA patients are associated with perfusion deficits using whole brain 320-detector-row CT perfusion, and to determine an association between ABCD2 score and perfusion deficit using whole brain perfusion. We retrospectively reviewed all TIA patients for CTP deficits from 2008-2010. Perfusion imaging was reviewed at admission; and it was determined if a perfusion deficit was present along with vascular territory involved. Of 364 TIA patients, 62 patients had CTP deficits. The largest group of patients had MCA territory involved with 48 of 62 patients (77.42%). The most common perfusion abnormality was increased TTP with 46 patients (74.19%). The ABCD2 score was reviewed in association with perfusion deficit. Increased age >60, severe hypertension (>180/100 mmHg), patients with speech abnormalities, and duration of symptoms >10 min were associated with a perfusion deficit but history of diabetes or minimal/moderate hypertension (140/90-179/99 mmHg) was not. There was no association between motor deficit and perfusion abnormality. Perfusion deficits are found in TIA patients using whole brain CTP and associated with components of the ABCD2 score.

  15. Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering

    OpenAIRE

    Sitek, Kevin R.; Cai, Shanqing; Beal, Deryk S.; Perkell, Joseph S.; Guenther, Frank H.; Ghosh, Satrajit S.

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had st...

  16. Decreased cerebellar-orbitofrontal connectivity correlates with stuttering severity: Whole-brain functional and structural connectivity associations with persistent developmental stuttering

    OpenAIRE

    Kevin Richard Sitek; Kevin Richard Sitek; Shanqing eCai; Shanqing eCai; Deryk Scott Beal; Deryk Scott Beal; Deryk Scott Beal; Deryk Scott Beal; Deryk Scott Beal; Joseph S Perkell; Joseph S Perkell; Frank eGuenther; Satrajit S Ghosh; Satrajit S Ghosh

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here, we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had ...

  17. Aberrant Functional Connectivity Architecture in Participants with Chronic Insomnia Disorder Accompanying Cognitive Dysfunction: A Whole-Brain, Data-Driven Analysis

    OpenAIRE

    Pang, Ran; Zhan, Yafeng; Zhang, Yunling; Guo, Rongjuan; Wang, Jialin; Guo, Xiao; Liu, Yong; Wang, Zhiqun; Li, Kuncheng

    2017-01-01

    Objectives: Although it is widely observed that chronic insomnia disorder (CID) is associated with cognitive impairment, the neurobiological mechanisms underlying this remain unclear. Prior neuroimaging studies have confirmed that a close correlation exists between functional connectivity and cognitive impairment. Based on this observation, in this study we used resting-state functional magnetic resonance imaging (rs-fMRI) to study the relationship between whole brain functional connectivity ...

  18. Disrupted Topological Organization in Whole-Brain Functional Networks of Heroin-Dependent Individuals: A Resting-State fMRI Study

    OpenAIRE

    Jiang, Guihua; Wen, Xue; Qiu, Yingwei; Zhang, Ruibin; Wang, Junjing; Li, Meng; Ma, Xiaofen; Tian, Junzhang; Huang, Ruiwang

    2013-01-01

    Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subj...

  19. A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Murat Demirtaş

    2017-01-01

    Full Text Available Alzheimer's disease (AD is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC of the subjects with preclinical Alzheimer's disease (PAD, mild cognitive impairment due to AD (MCI and mild dementia due to Alzheimer's disease (AD, the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1−42 total tau (t-tau and phosphorylated tau (p-tau. CSF Aβ1−42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1−42. APOE4 carriership showed no significant correlations with the connectivity measures.

  20. Whole Brain Radiotherapy With Hippocampal Avoidance and Simultaneous Integrated Boost for 1-3 Brain Metastases: A Feasibility Study Using Volumetric Modulated Arc Therapy

    International Nuclear Information System (INIS)

    Hsu, Fred; Carolan, Hannah; Nichol, Alan; Cao, Fred; Nuraney, Nimet; Lee, Richard; Gete, Ermias; Wong, Frances; Schmuland, Moira; Heran, Manraj; Otto, Karl

    2010-01-01

    Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) to deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) for one to three brain metastases. Methods and Materials: Ten patients previously treated with stereotactic radiosurgery for one to three brain metastases underwent repeat planning using VMAT. The whole brain prescription dose was 32.25 Gy in 15 fractions, and SIB doses to brain metastases were 63 Gy to lesions ≥2.0 cm and 70.8 Gy to lesions 2 . Plans were optimized for conformity and target coverage while minimizing hippocampal and ocular doses. Plans were evaluated on target coverage, prescription isodose to target volume ratio, conformity number, homogeneity index, and maximum dose to prescription dose ratio. Results: Ten patients had 18 metastases. Mean values for the brain metastases were as follows: conformity number = 0.73 ± 0.10, target coverage = 0.98 ± 0.01, prescription isodose to target volume = 1.34 ± 0.19, maximum dose to prescription dose ratio = 1.09 ± 0.02, and homogeneity index = 0.07 ± 0.02. For the whole brain, the mean target coverage and homogeneity index were 0.960 ± 0.002 and 0.39 ± 0.06, respectively. The mean hippocampal dose was 5.23 ± 0.39 Gy 2 . The mean treatment delivery time was 3.6 min (range, 3.3-4.1 min). Conclusions: VMAT was able to achieve adequate whole brain coverage with conformal hippocampal avoidance and radiosurgical quality dose distributions for one to three brain metastases. The mean delivery time was under 4 min.

  1. Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects

    International Nuclear Information System (INIS)

    Eusebio, Alexandre; Azulay, Jean-Philippe; Ceccaldi, Mathieu; Girard, Nadine; Mundler, Olivier; Guedj, Eric

    2012-01-01

    Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [ 123 I]FP-CIT SPECT in healthy subjects. We performed a whole-brain [ 123 I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p < 0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79 years. We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices. This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders. (orig.)

  2. Voxel-based analysis of whole-brain effects of age and gender on dopamine transporter SPECT imaging in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Eusebio, Alexandre; Azulay, Jean-Philippe [APHM, Hopital de la Timone, Service de Neurologie et Pathologie du Mouvement, Marseille (France); CNRS, Aix-Marseille Univ, Institut de Neurosciences de la Timone, Marseille (France); Ceccaldi, Mathieu [APHM, Hopital de la Timone, Service de Neurologie et de Neuropsychologie, Marseille (France); Aix-Marseille Univ, UMR Inserm 1106, Institut de Neurosciences des Systemes, Marseille (France); Girard, Nadine [APHM, Hopital de la Timone, Service de Neuroradiologie diagnostique et interventionnelle, Marseille (France); Mundler, Olivier [APHM, Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Aix-Marseille Univ, CERIMED, Marseille (France); Guedj, Eric [CNRS, Aix-Marseille Univ, Institut de Neurosciences de la Timone, Marseille (France); APHM, Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France); Aix-Marseille Univ, CERIMED, Marseille (France)

    2012-11-15

    Several studies have shown age- and gender-related differences in striatal dopamine transporter (DaT) binding. These studies were based on a striatal region on interest approach that may have underestimated these effects and could not evaluate extrastriatal regions. Our aim was to determine the effects at the voxel level of age and gender on whole-brain DaT distribution using [{sup 123}I]FP-CIT SPECT in healthy subjects. We performed a whole-brain [{sup 123}I]FP-CIT SPECT voxel-based analysis using SPM8 and a standardized normalization template (p < 0.05, corrected using the false discovery rate method) in 51 healthy subjects aged from 21 to 79 years. We found an age-related DaT binding decrease in the striatum, anterior cingulate/medial frontal cortices and insulo-opercular cortices. Also DaT binding ratios were higher in women than men in the striatum and opercular cortices. This study showed both striatal and extrastriatal age-related and gender-related differences in DaT binding in healthy subjects using a whole-brain voxel-based non-a priori approach. These differences highlight the need for careful age and gender matching in DaT analyses of neuropsychiatric disorders. (orig.)

  3. The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients

    International Nuclear Information System (INIS)

    Zhang, Bo; Gu, Guo-jun; Jiang, Hong; Guo, Yi; Shen, Xing; Li, Bo; Zhang, Wei

    2017-01-01

    To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. (orig.)

  4. The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Gu, Guo-jun; Jiang, Hong; Guo, Yi [Medical School of Tongji University, Department of Medical Imaging, Tongji Hospital, Shanghai (China); Shen, Xing [Traditional Chinese Hospital, Department of Radiology, Kun Shan, Jiangsu Province (China); Li, Bo; Zhang, Wei [Medical School of Jiaotong University, Department of Medical Imaging, Renji Hospital, Shanghai (China)

    2017-11-15

    To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. (orig.)

  5. Hybrid [{sup 18}F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): Preliminary results in non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Heusch, Philipp [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, D-45147 Essen (Germany); Köhler, Jens [Univ Duisburg-Essen, Medical Faculty, Department of Medical Oncology, D-45147 Essen (Germany); Wittsack, Hans-Joerg [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Heusner, Till A., E-mail: Heusner@med.uni-duesseldorf.de [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Buchbender, Christian [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany); Poeppel, Thorsten D. [Univ Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, D-45147 Essen (Germany); Nensa, Felix; Wetter, Axel [Univ Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, D-45147 Essen (Germany); Gauler, Thomas [Univ Duisburg-Essen, Medical Faculty, Department of Medical Oncology, D-45147 Essen (Germany); Hartung, Verena [Univ Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, D-45147 Essen (Germany); Lanzman, Rotem S. [Univ Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, D-40225 Dusseldorf (Germany)

    2013-11-01

    Purpose: To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer. Material and methods: 15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm{sup 2}) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV{sub max}; SUV{sub mean}). A region of interest (ROI) was manually drawn around the tumor on b = 0 images and then transferred to the corresponding parameter maps to assess ADC{sub mono}, D{sub app} and K{sub app}. To assess the goodness of the mathematical fit R{sup 2} was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R{sup 2}). Results: T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC{sub mono} was 2.11 ± 1.24 × 10{sup −3} mm{sup 2}/s, D{sub app} was 2.46 ± 1.29 × 10{sup −3} mm{sup 2}/s and mean K{sub app} was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R{sup 2} = 0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R{sup 2} = 0.96) (p < 0.001). SUV{sub max} and SUV{sub mean} of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC{sub mono} as well as D{sub app} exhibited a significant inverse correlation with the SUV{sub max} (ADC{sub mono}: R = −0.67; p < 0.01; D{sub app}: R = −0.69; p < 0.01) as well as with SUV{sub mean} assessed by FDG-PET/MRI (ADC{sub mono}: R

  6. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  7. Volume changes of whole brain gray matter in pediatric patients with Tourette syndrome: evidence from voxel-based morphometry

    International Nuclear Information System (INIS)

    Liu Yue; Peng Yun; Gao Peiyi; Nie Binbin; Lu Chuankai; Zhang Liping; Ji Zhiying; Yin Guangheng; Yu Tong; Shan Baoci

    2012-01-01

    Objectives: To identify the related abnormalities of gray matter in pediatric patients with Tourette syndrome (TS) by using the optimized voxel-based morphometry (VBM). Methods: Three dimensional T 1 WI was acquired in 31 TS children (28 boys, 3 girts, mean age 8 years, range 4-15 years) and 50 age- and sex-matched controls on a 1.5 Tesla Philips scanner. Images were pre-processed and analyzed using a version of VBM 2 in SPM 2. The whole brain gray matter volume was compared between the study and control group by using t-test. Multivariate linear regression analysis was used for analyzing the correlation between the change of grey matter volume within each brain region (mm 3 ) and YGTSS score and course of disease of TS patients. Statistical analyses were performed by using SPSS 13.0. Results: Using VBM, significant increases in gray matter volumes in left superior parietal lobule, right cerebellar hemisphere and left parahippocampal gyrus were detected in TS patients, and the volume changes were 4059, 2126 and 84 mm 3 (t=3.93, 3.71, 3.58, P<0.05) respectively. Compared to the control group, decreased grey matter volumes were found in medulla and left pons, and the volume changes were 213 and 117 mm 3 (t=3.53, 3.48, P<0.05)respectively. Tic severity was not correlated with any volume changes of gray matter in brain (P>0.05, a small volume correction, KE ≥ 10 voxel). Tic course was negatively correlated with the gray matter volume of left parahippocampal gyrus (Beta =-0.391, P=0.039). Conclusions: Using VBM technique, the gray matter abnormalities can be revealed in TS patients without obvious lesions on conventional MR imaging. The increasing volume of temporal and parietal lobes and cerebellar may be an adaptive anatomical change in response to experiential demand. The gray matter volume of the parahippocampal gyrus may be used as one potential objective index for evaluating the prognosis of TS. (authors)

  8. Whole-brain background-suppressed pCASL MRI with 1D-accelerated 3D RARE Stack-Of-Spirals readout.

    Directory of Open Access Journals (Sweden)

    Marta Vidorreta

    Full Text Available Arterial Spin Labeled (ASL perfusion MRI enables non-invasive, quantitative measurements of tissue perfusion, and has a broad range of applications including brain functional imaging. However, ASL suffers from low signal-to-noise ratio (SNR, limiting image resolution. Acquisitions using 3D readouts are optimal for background-suppression of static signals, but can be SAR intensive and typically suffer from through-plane blurring. In this study, we investigated the use of accelerated 3D readouts to obtain whole-brain, high-SNR ASL perfusion maps and reduce SAR deposition. Parallel imaging was implemented along the partition-encoding direction in a pseudo-continuous ASL sequence with background-suppression and 3D RARE Stack-Of-Spirals readout, and its performance was evaluated in three small cohorts. First, both non-accelerated and two-fold accelerated single-shot versions of the sequence were evaluated in healthy volunteers during a motor-photic task, and the performance was compared in terms of temporal SNR, GM-WM contrast, and statistical significance of the detected activation. Secondly, single-shot 1D-accelerated imaging was compared to a two-shot accelerated version to assess benefits of SNR and spatial resolution for applications in which temporal resolution is not paramount. Third, the efficacy of this approach in clinical populations was assessed by applying the single-shot 1D-accelerated version to a larger cohort of elderly volunteers. Accelerated data demonstrated the ability to detect functional activation at the subject level, including cerebellar activity, without loss in the perfusion signal temporal stability and the statistical power of the activations. The use of acceleration also resulted in increased GM-WM contrast, likely due to reduced through-plane partial volume effects, that were further attenuated with the use of two-shot readouts. In a clinical cohort, image quality remained excellent, and expected effects of age and sex

  9. Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

    Energy Technology Data Exchange (ETDEWEB)

    Farris, Michael, E-mail: mfarris@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); McTyre, Emory R.; Cramer, Christina K.; Hughes, Ryan; Randolph, David M.; Ayala-Peacock, Diandra N.; Bourland, J. Daniel [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Ruiz, Jimmy [Department of Medicine - Hematology & Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Watabe, Kounosuke [Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Laxton, Adrian W.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Zhou, Xiaobo [Center for Bioinformatics & Systems Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States)

    2017-05-01

    Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

  10. Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

    International Nuclear Information System (INIS)

    Farris, Michael; McTyre, Emory R.; Cramer, Christina K.; Hughes, Ryan; Randolph, David M.; Ayala-Peacock, Diandra N.; Bourland, J. Daniel; Ruiz, Jimmy; Watabe, Kounosuke; Laxton, Adrian W.; Tatter, Stephen B.; Zhou, Xiaobo; Chan, Michael D.

    2017-01-01

    Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

  11. Is whole brain radiation therapy needed for all patients with newly diagnosed brain metastases undergoing stereotactic radiosurgery?

    International Nuclear Information System (INIS)

    Suh, John H.; Barnett, Gene H.; Miller, David W.; Kupelian, Patrick A.; Cohen, Bruce H.

    1997-01-01

    PURPOSE: Since whole brain radiation therapy (WBRT) carries risks for long term survivors of brain metastases, some have advocated the use of stereotactic radiosurgery (SRS) alone for patients with brain metastases. We retrospectively reviewed our results of stereotactic radiosurgery (SRS) with immediate or delayed WBRT. MATERIALS/METHODS: From March 1990 to December 1996, linear accelerator-based SRS was performed on patients with Karnofsky score ≥ 70 and asymptomatic or mildly symptomatic brain metastases < 4 cm diameter. After excluding those patients with recurrent disease, 87 patients with 106 metastatic lesions (72 pts- single or solitary lesion, 13 pts- 2 lesions, 1 pt- 3 lesions, and 1 pt- 5 lesions) remained for analysis. The use of WBRT was dependent on physician preference but was given to all patients who developed local or regional failure after SRS. Survival was measured from the date of SRS until death or last follow-up using Kaplan-Meier method. Freedom from progression (FFP) was defined as no local or regional brain failure on follow-up radiographs and was measured from the date of SRS. RESULTS: Prognostic variables (age, sex, initial KPS, systemic disease, and extent of surgical resection) were similar for the 40 patients in the immediate WBRT group (iWBRT) and for the 47 patients in the delayed WBRT group (dWBRT). With a median follow-up of 5.8 months, no significant difference in median survival (6.9 months for both groups) was noted. On multivariate analysis, absence of systemic disease (p=0.008) and KPS 90-100 (p=0.001) were the only significant predictors for survival. For the 29 patients with a minimum KPS of 90 and no systemic disease, the median survival was 17.8 months. For those patients with a solitary lesion (no systemic disease), there was a trend for better median survival for the iWBRT group (22.8 months) versus the dWBRT group (9.3 months), p=0.06. FFP data was available on 78 patients (97 lesions). A significant difference was

  12. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  13. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg; Ganzhirnbestrahlung bei Hirnmetastasen von 2005 bis 2011 in der Klinik fuer Strahlenheilkunde des Universitaetsklinikums Freiburg

    Energy Technology Data Exchange (ETDEWEB)

    Hintz, Mandy

    2017-10-01

    Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

  14. Endometrial Stromal Sarcoma of the Uterus: Magnetic Resonance Imaging Findings Including Apparent Diffusion Coefficient Value and Its Correlation With Ki-67 Expression.

    Science.gov (United States)

    Li, Hai Ming; Liu, Jia; Qiang, Jin Wei; Gu, Wei Yong; Zhang, Guo Fu; Ma, Feng Hua

    2017-11-01

    This study aimed to investigate the conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) features of endometrial stromal sarcoma (ESS) including a preliminary investigation of the correlation between the apparent diffusion coefficient (ADC) value and Ki-67 expression. The clinical and MRI data of 15 patients with ESS confirmed by surgery and pathology were analyzed retrospectively. The conventional MR morphological features, signal intensity on DWI, ADC value (n = 14), and clinicopathological marker Ki-67 (n = 13) were evaluated. Of 15 patients with ESS, 13 tumors were low-grade ESS (LGESS), and the remaining 2 were high-grade ESS (HGESS); 9 tumors were located in the myometrium, 5 were located in the endometrium and/or cervical canal, and 1 was located in extrauterine. Thirteen (87%) of 15 tumors showed a homo- or heterogeneous isointensity on T1-weighted imaging and a heterogeneous hyperintensity on T2-weighted imaging. The hypointense bands were observed in 11 tumors (73%) on T2-weighted imaging. The degenerations (cystic/necrosis/hemorrhage) were observed in 7 LGESS tumors and 2 HGESS tumors. The DWI hyperintensity was observed in 13 tumors (93%) and isointensity in remaining 1. The mean ADC value of the solid components in 14 ESSs was (1.05 ± 0.20) × 10mm/s. The contrast-enhanced MRI showed an obvious enhancement in 14 tumors (93%) (heterogeneous in 7 LGESSs and 2 HGESSs; homogeneous in 5 LGESSs). The ADC value was inversely correlated with the Ki-67 expression (r = -0.613, P = 0.026). Patients with ESS showed some characteristics on conventional MRI and DWI, and there was an inverse correlation between the ADC value and Ki-67 expression.

  15. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2012-06-15

    To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

  16. Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.; Tewatia, Dinesh; Rowley, Howard; Kuo, John S.; Khuntia, Deepak; Tome, Wolfgang A.

    2010-01-01

    Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume was 3.3 cm 3 , occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy 2 using helical tomotherapy and by 81% to 0.73 Gy 2 using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

  17. Field in field technique in two-dimensional planning for whole brain irradiation; Tecnica field in field em planejamentos bidimensionais para irradiacao de cerebro total

    Energy Technology Data Exchange (ETDEWEB)

    Castro, A.L.S.; Campos, T.P.R., E-mail: radioterapia.andre@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Departamento de Engenharia Nuclear

    2016-11-01

    Radiotherapy is the most used clinical method used for brain metastases treatment, the most frequent secondary tumors provided by breast, lung and melanomas as primary origin. The protocols often use high daily doses and, depending on the irradiation technique there is high probability of complications in health tissues. In order to minimize adverse effects, it is important the dosimetric analysis of three-dimensional radiotherapy planning through tomographic images or, concerning to the 2D simulations, by the application of techniques that optimize dose distribution by increasing the homogeneity. The study aimed to compare the 2D and 3D conformal planning for total brain irradiation in a individual equivalent situation and evaluate the progress of these planning applying the field in field technique. The methodology consisted of simulating a two-dimensional planning, reproduce it on a set of tomographic images and compare it with the conformal plan for two fields and four fields (field in field). The results showed no significant difference between 2D and 3D planning for whole brain irradiation, and the field in field technique significantly improved the dose distribution in brain volume compared with two fields for the proposal situation. As conclusion, the two-dimensional plane for the four fields described was viable for whole brain irradiation in the treatment of brain metastases at the proposal situation. (author)

  18. Effects of intravenous administration of bone marrow stromal stem cells on cognitive impairment of the whole-brain irradiated rat models

    International Nuclear Information System (INIS)

    Ding Weijun; Wang Jianhua; Zhu Min; Chen Baoguo; Wang Yang

    2007-01-01

    Objective: To explore the effect of intravenous infusion of bone marrow stromal stem cells(MSCs) on cognitive function of rats after whole brain irradiation. Methods: MSCs were isolated and cultured from adult rats. After Sprague-Dawly female rats were anaesthetized with chloral hydrate, their whole cerebrum was irradiated with a single dose of 20 Gy by 6 MV X-ray. Seven days after irradiation, 4 x 106 Hoechst33342-1abelled MSCs were intravenously injected into the tail vein of these rats. Four and 8 weeks after transplantation, the learning and memorizing ability was measured with the Y maze test. Immunohistochemical method was used to identify MSCs or ceils derived from MSCs in the brain. Results: The learning and memorizing ability of irradiation groups were significantly different from that of normal control group (P < 0.01). Significant improvement of cognitive impairment was observed in rats treated with MSCs at 4 and 8 weeks after transplantation as compared with the controll groups (P<0.05). This showed that the MSCs survived and were localized to the brain tissue. The number of Hoechst33342 immunohistofluorescence positive cells and double-immunostaining cells significantly decreased in 8 weeks group as compared with the 4 weeks group. Conclusion: Marrow stromal stem cells delivered to the irradiation brain tissue through intravenous route improve the cognitive impairment after whole brain irradiation. These cells may survive and differentiate in the brain tissue of irradiated rats. (authors)

  19. Optimization of multiple coils immersed in a conducting liquid for half-hemisphere or whole-brain deep transcranial magnetic stimulation: a simulation study.

    Science.gov (United States)

    Sousa, Sónia C P; Almeida, Jorge; Cavaleiro Miranda, Pedro; Salvador, Ricardo; Silvestre, João; Simões, Hugo; Crespo, Paulo

    2014-01-01

    Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its wider use in the treatment of several neurologic diseases has been hindered by its inability to stimulate deep-brain regions. This is mainly due to the physical limiting effect arising from the presence of surface discontinuities, particularly between the scalp and air. Here, we present the optimization of a system of large multiple coils for whole-brain and half-hemisphere deep TMS, termed orthogonal configuration. COMSOL(®)-based simulations show that the system is capable of reaching the very center of a spherical brain phantom with 58% induction relative to surface maximum. Such penetration capability surpasses to the best of our knowledge that of existing state of the art TMS systems. This induction capability strongly relies on the immersion of the stimulating coils and part of the head of the patient in a conducting liquid (e.g. simple saline solution). We show the impact of the presence of this surrounding conducting liquid by comparing the performance of our system with and without such liquid. In addition, we also compare the performance of the proposed coil with that of a circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its whole-brain stimulation capability (e.g. potentially useful for prophylaxis of epileptic patients) the system is also able to stimulate mainly one brain hemisphere, which may be useful in stroke rehabilitation, among other applications.

  20. Large-Scale Network Analysis of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury: A Comparative Study.

    Science.gov (United States)

    Kaushal, Mayank; Oni-Orisan, Akinwunmi; Chen, Gang; Li, Wenjun; Leschke, Jack; Ward, Doug; Kalinosky, Benjamin; Budde, Matthew; Schmit, Brian; Li, Shi-Jiang; Muqeet, Vaishnavi; Kurpad, Shekar

    2017-09-01

    Network analysis based on graph theory depicts the brain as a complex network that allows inspection of overall brain connectivity pattern and calculation of quantifiable network metrics. To date, large-scale network analysis has not been applied to resting-state functional networks in complete spinal cord injury (SCI) patients. To characterize modular reorganization of whole brain into constituent nodes and compare network metrics between SCI and control subjects, fifteen subjects with chronic complete cervical SCI and 15 neurologically intact controls were scanned. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI). Correlation analysis was performed between every ROI pair to construct connectivity matrices and ROIs were categorized into distinct modules. Subsequently, local efficiency (LE) and global efficiency (GE) network metrics were calculated at incremental cost thresholds. The application of a modularity algorithm organized the whole-brain resting-state functional network of the SCI and the control subjects into nine and seven modules, respectively. The individual modules differed across groups in terms of the number and the composition of constituent nodes. LE demonstrated statistically significant decrease at multiple cost levels in SCI subjects. GE did not differ significantly between the two groups. The demonstration of modular architecture in both groups highlights the applicability of large-scale network analysis in studying complex brain networks. Comparing modules across groups revealed differences in number and membership of constituent nodes, indicating modular reorganization due to neural plasticity.

  1. A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

    Science.gov (United States)

    Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

    2010-09-01

    Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

  2. [Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

    Science.gov (United States)

    Zhang, Lingling; Liu, Bin; Xu, Yangwen; Yang, Ming; Feng, Yuan; Huang, Yaqing; Huan, Zhichun; Hou, Zhaorui

    2015-02-03

    To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

  3. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases

    Science.gov (United States)

    Brown, Paul D.; Jaeckle, Kurt; Ballman, Karla V.; Farace, Elana; Cerhan, Jane H.; Anderson, S. Keith; Carrero, Xiomara W.; Barker, Fred G.; Deming, Richard; Burri, Stuart H.; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W.; Pollock, Bruce E.; Galanis, Evanthia; Buckner, Jan C.; Asher, Anthony L.

    2017-01-01

    IMPORTANCE Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, −0.1 vs −12.0 points; mean difference, 11.9; 95% CI, 4.8–19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2–5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, −1.5 points for SRS alone vs −4

  4. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.

    Science.gov (United States)

    Brown, Paul D; Jaeckle, Kurt; Ballman, Karla V; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Barker, Fred G; Deming, Richard; Burri, Stuart H; Ménard, Cynthia; Chung, Caroline; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2016-07-26

    Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median

  5. Predictive value of diffusion-weighted imaging without and with including contrast-enhanced magnetic resonance imaging in image analysis of head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Noij, Daniel P., E-mail: d.noij@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Pouwels, Petra J.W., E-mail: pjw.pouwels@vumc.nl [Department of Physics and Medical Technology, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Ljumanovic, Redina, E-mail: rljumanovic@adventh.org [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Knol, Dirk L., E-mail: dirklknol@gmail.com [Department of Epidemiology and Biostatistics, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Doornaert, Patricia, E-mail: p.doornaert@vumc.nl [Department of Radiation Oncology, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Bree, Remco de, E-mail: r.debree@vumc.nl [Department of Otolaryngology – Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Castelijns, Jonas A., E-mail: j.castelijns@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands); Graaf, Pim de, E-mail: p.degraaf@vumc.nl [Department of Radiology and Nuclear Medicine, VU University Medical Center, De Boelelaan 1117, Amsterdam, Noord-Holland (Netherlands)

    2015-01-15

    Highlights: • Primary tumor volume and lymph node ADC1000 are predictors of survival. • CE-T1WI does not improve the prognostic capacity of DWI. • Using CE-T1WI for ROI placement results in lower interobserver agreement. - Abstract: Objectives: To assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT). Methods: Pretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0–750 s/mm{sup 2} (ADC{sub 750}) and 0–1000 s/mm{sup 2} (ADC{sub 1000}). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC{sub 750} and ADC{sub 1000}. Lesion volumes and ADC-values were related to DFS using Cox regression analysis. Results: Median follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75–0.83, respectively; lymph node: 0.81–0.83 and 0.61–0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P < 0.001). Tumor volume (sensitivity: 73%; specificity: 57%) and lymph node ADC{sub 1000} (sensitivity: 71–79%; specificity: 77–79%) were independent significant predictors of DFS without and with including CE-T1WI (P < 0.05). Conclusions: Pretreatment primary tumor volume and lymph node ADC{sub 1000} were significant independent predictors of DFS in HNSCC treated with (C)RT. DFS could be predicted from ADC-values acquired without and with including CE-T1WI in image analysis. The inclusion of CE-T1WI did not result in significant improvements in the predictive value of

  6. Switches for multiple behavioral states and a viral-based approach to non-invasive whole-brain cargo delivery (Conference Presentation)

    Science.gov (United States)

    Gradinaru, Viviana

    2017-05-01

    Over the past years we have worked on: (1) Viral-based approaches to non-invasive whole-brain cargo delivery: Genetically-encoded tools that can be used to visualize, monitor, and modulate mammalian neurons are revolutionizing neuroscience. These tools are particularly powerful in rodents and invertebrate models where intersectional transgenic strategies are available to restrict their expression to defined cell populations. However, use of genetic tools in non-transgenic animals is often hindered by the lack of vectors capable of safe, efficient, and specific delivery to the desired cellular targets. To begin to address these challenges, we have developed an in vivo Cre-based selection platform (CREATE) for identifying adeno-associated viruses (AAVs) that more efficiently transduce genetically defined cell populations. Our platform's novelty and power arises from the additional selective pressure imparted by a recovery step that amplifies only those capsid variants that have functionally transduced a genetically-defined, Cre-expressing target cell population. The Cre-dependent capsid recovery works within heterogeneous tissue samples without the need for additional steps such as selective capsid recovery approaches that require cell sorting or secondary adenovirus infection. As a first test of the CREATE platform, we selected for viruses that transduced the brain after intravascular delivery and found a novel vector, AAV-PHP.B, that is 40- to 90-fold more efficient at transducing the brain than the current standard, AAV9. AAV-PHP.B transduces most neuronal types and glia across the brain. We also demonstrate here how whole-body tissue clearing can facilitate transduction maps of systemically delivered genes. Since CNS disorders are notoriously challenging due to the restrictive nature of the blood brain barrier our discovery that recombinant vectors can be engineered to overcome this barrier is enabling for the whole field. With the exciting advances in gene

  7. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

    2013-01-01

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  8. Mathematical modeling of synthesis gas fueled electrochemistry and transport including H2/CO co-oxidation and surface diffusion in solid oxide fuel cell

    Science.gov (United States)

    Bao, Cheng; Jiang, Zeyi; Zhang, Xinxin

    2015-10-01

    Fuel flexibility is a significant advantage of solid oxide fuel cell (SOFC). A comprehensive macroscopic framework is proposed for synthesis gas (syngas) fueled electrochemistry and transport in SOFC anode with two main novelties, i.e. analytical H2/CO electrochemical co-oxidation, and correction of gas species concentration at triple phase boundary considering competitive absorption and surface diffusion. Staring from analytical approximation of the decoupled charge and mass transfer, we present analytical solutions of two defined variables, i.e. hydrogen current fraction and enhancement factor. Giving explicit answer (rather than case-by-case numerical calculation) on how many percent of the current output contributed by H2 or CO and on how great the water gas shift reaction plays role on, this approach establishes at the first time an adaptive superposition mechanism of H2-fuel and CO-fuel electrochemistry for syngas fuel. Based on the diffusion equivalent circuit model, assuming series-connected resistances of surface diffusion and bulk diffusion, the model predicts well at high fuel utilization by keeping fixed porosity/tortuosity ratio. The model has been validated by experimental polarization behaviors in a wide range of operation on a button cell for H2-H2O-CO-CO2-N2 fuel systems. The framework could be helpful to narrow the gap between macro-scale and meso-scale SOFC modeling.

  9. Unusual acute and delayed skin reactions during and after whole-brain radiotherapy in combination with the BRAF inhibitor vemurafenib. Two case reports

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, B.; Roedel, C.; Weiss, C. [Johann Wolfgang Goethe-University Hospital, Department of Radiation Oncology, Frankfurt am Main (Germany); Meissner, M.; Wolter, M. [Johann Wolfgang Goethe-University Hospital, Department of Dermatology, Frankfurt am Main (Germany)

    2014-02-15

    Besides radiotherapy (RT) and surgery, the introduction of BRAF inhibitors like vemurafenib has provided new opportunities for treatment of patients with metastasized malignant melanomas. RT and vemurafenib are being increasingly used concurrently, although little is known about the potential side effects of this combination. Vemurafenib is known to cause severe cutaneous skin reactions such as phototoxicity and evidence is accumulating that RT may further enhance these side effects. We report two cases of unusual skin reactions occurring during and after treatment with a combination of vemurafenib and whole-brain irradiation in patients with cerebral metastases arising from malignant melanomas. One case report describes excessive acute radiodermatitis which arose during whole-brain irradiation in combination with vemurafenib. The second describes a late skin reaction occurring approximately 30 days after completion of RT. These two case reports show that combination of both treatment modalities is possible, but requires close monitoring of patients and good interdisciplinary collaboration. (orig.) [German] Neben der Strahlentherapie und Chirurgie stellt die Einfuehrung von BRAF-Inhibitoren wie Vemurafenib eine neue Moeglichkeit zur Behandlung von metastasierten malignen Melanomen dar und immer haeufiger kommt eine Kombination aus Strahlentherapie und Vemurafenib zum Einsatz. Bislang ist wenig bekannt ueber potentielle Nebenwirkungen, die sich aus einer Kombination beider Therapieoptionen ergeben koennen. Vemurafenib kann zu schweren kutanen Nebenwirkungen wie z. B. Phototoxizitaet fuehren und es haeufen sich Hinweise, dass die Strahlentherapie diese Nebenwirkungen verstaerken kann. Wir berichten ueber zwei Faelle ungewoehnlicher Hautreaktionen waehrend und nach einer Ganzhirnbestrahlung in Kombination mit Vemurafenib. Ein Fall beschreibt eine akute und ueberschiessende Radiodermatitis unter fortlaufender Radiotherapie und der andere Fall beschreibt eine spaete

  10. Generation of Individual Whole-Brain Atlases With Resting-State fMRI Data Using Simultaneous Graph Computation and Parcellation.

    Science.gov (United States)

    Wang, J; Hao, Z; Wang, H

    2018-01-01

    The human brain can be characterized as functional networks. Therefore, it is important to subdivide the brain appropriately in order to construct reliable networks. Resting-state functional connectivity-based parcellation is a commonly used technique to fulfill this goal. Here we propose a novel individual subject-level parcellation approach based on whole-brain resting-state functional magnetic resonance imaging (fMRI) data. We first used a supervoxel method known as simple linear iterative clustering directly on resting-state fMRI time series to generate supervoxels, and then combined similar supervoxels to generate clusters using a clustering method known as graph-without-cut (GWC). The GWC approach incorporates spatial information and multiple features of the supervoxels by energy minimization, simultaneously yielding an optimal graph and brain parcellation. Meanwhile, it theoretically guarantees that the actual cluster number is exactly equal to the initialized cluster number. By comparing the results of the GWC approach and those of the random GWC approach, we demonstrated that GWC does not rely heavily on spatial structures, thus avoiding the challenges encountered in some previous whole-brain parcellation approaches. In addition, by comparing the GWC approach to two competing approaches, we showed that GWC achieved better parcellation performances in terms of different evaluation metrics. The proposed approach can be used to generate individualized brain atlases for applications related to cognition, development, aging, disease, personalized medicine, etc. The major source codes of this study have been made publicly available at https://github.com/yuzhounh/GWC.

  11. Whole-brain intracranial vessel wall imaging at 3 Tesla using cerebrospinal fluid-attenuated T1-weighted 3D turbo spin echo.

    Science.gov (United States)

    Fan, Zhaoyang; Yang, Qi; Deng, Zixin; Li, Yuxia; Bi, Xiaoming; Song, Shlee; Li, Debiao

    2017-03-01

    Although three-dimensional (3D) turbo spin echo (TSE) with variable flip angles has proven to be useful for intracranial vessel wall imaging, it is associated with inadequate suppression of cerebrospinal fluid (CSF) signals and limited spatial coverage at 3 Tesla (T). This work aimed to modify the sequence and develop a protocol to achieve whole-brain, CSF-attenuated T 1 -weighted vessel wall imaging. Nonselective excitation and a flip-down radiofrequency pulse module were incorporated into a commercial 3D TSE sequence. A protocol based on the sequence was designed to achieve T 1 -weighted vessel wall imaging with whole-brain spatial coverage, enhanced CSF-signal suppression, and isotropic 0.5-mm resolution. Human volunteer and pilot patient studies were performed to qualitatively and quantitatively demonstrate the advantages of the sequence. Compared with the original sequence, the modified sequence significantly improved the T 1 -weighted image contrast score (2.07 ± 0.19 versus 3.00 ± 0.00, P = 0.011), vessel wall-to-CSF contrast ratio (0.14 ± 0.16 versus 0.52 ± 0.30, P = 0.007) and contrast-to-noise ratio (1.69 ± 2.18 versus 4.26 ± 2.30, P = 0.022). Significant improvement in vessel wall outer boundary sharpness was observed in several major arterial segments. The new 3D TSE sequence allows for high-quality T 1 -weighted intracranial vessel wall imaging at 3 T. It may potentially aid in depicting small arteries and revealing T 1 -mediated high-signal wall abnormalities. Magn Reson Med 77:1142-1150, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Prognostic factors for survival and radiation necrosis after stereotactic radiosurgery alone or in combination with whole brain radiation therapy for 1–3 cerebral metastases

    International Nuclear Information System (INIS)

    Schüttrumpf, Lars Hendrik; Niyazi, Maximilian; Nachbichler, Silke Birgit; Manapov, Farkhad; Jansen, Nathalie; Siefert, Axel; Belka, Claus

    2014-01-01

    In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. 340 patients with 1–3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS ≤ 70: 122 days; KPS > 70: 342 days), for RPA (recursive partitioning analysis) class (RPA class I: 1800 days; RPA class II: 281 days; RPA class III: 130 days), irradiated volume (≤2.5 ml: 354 days; > 2.5 ml: 234 days), prescribed dose (≤18 Gy: 235 days; > 18 Gy: 351 days), gender (male: 235 days; female: 327 days) and whole brain radiotherapy (+WBRT: 341 days/-WBRT: 231 days). In multivariate analysis significance was confirmed for KPS, RPA class and gender. MRI and clinical symptoms suggested radiation necrosis in 21 patients after SRS +/− whole brain radiotherapy (WBRT). In five patients clinically relevant radiation necrosis was confirmed by PET imaging. SRS alone or in combination with WBRT represents a feasible option as initial treatment for patients with brain metastases; however a significant subset of patients may develop neurological complications. Performance status, RPA class and gender were identified to predict improved survival in cerebral metastasized patients

  13. Identifying the Alteration Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-Brain Voxel-Wise Degree Analysis.

    Science.gov (United States)

    Deng, Yanjia; Liu, Kai; Shi, Lin; Lei, Yi; Liang, Peipeng; Li, Kuncheng; Chu, Winnie C W; Wang, Defeng

    2016-01-01

    Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer's disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alteration patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset, and the progression was determined based on a 3-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a "severe" presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective evidence and an indicator

  14. Mapping whole-brain activity with cellular resolution by light-sheet microscopy and high-throughput image analysis (Conference Presentation)

    Science.gov (United States)

    Silvestri, Ludovico; Rudinskiy, Nikita; Paciscopi, Marco; Müllenbroich, Marie Caroline; Costantini, Irene; Sacconi, Leonardo; Frasconi, Paolo; Hyman, Bradley T.; Pavone, Francesco S.

    2016-03-01

    Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.

  15. Generation of Individual Whole-Brain Atlases With Resting-State fMRI Data Using Simultaneous Graph Computation and Parcellation

    Directory of Open Access Journals (Sweden)

    J. Wang

    2018-05-01

    Full Text Available The human brain can be characterized as functional networks. Therefore, it is important to subdivide the brain appropriately in order to construct reliable networks. Resting-state functional connectivity-based parcellation is a commonly used technique to fulfill this goal. Here we propose a novel individual subject-level parcellation approach based on whole-brain resting-state functional magnetic resonance imaging (fMRI data. We first used a supervoxel method known as simple linear iterative clustering directly on resting-state fMRI time series to generate supervoxels, and then combined similar supervoxels to generate clusters using a clustering method known as graph-without-cut (GWC. The GWC approach incorporates spatial information and multiple features of the supervoxels by energy minimization, simultaneously yielding an optimal graph and brain parcellation. Meanwhile, it theoretically guarantees that the actual cluster number is exactly equal to the initialized cluster number. By comparing the results of the GWC approach and those of the random GWC approach, we demonstrated that GWC does not rely heavily on spatial structures, thus avoiding the challenges encountered in some previous whole-brain parcellation approaches. In addition, by comparing the GWC approach to two competing approaches, we showed that GWC achieved better parcellation performances in terms of different evaluation metrics. The proposed approach can be used to generate individualized brain atlases for applications related to cognition, development, aging, disease, personalized medicine, etc. The major source codes of this study have been made publicly available at https://github.com/yuzhounh/GWC.

  16. Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.

    Science.gov (United States)

    Kim, Michelle M; Parmar, Hemant; Cao, Yue; Pramanik, Priyanka; Schipper, Matthew; Hayman, James; Junck, Larry; Mammoser, Aaron; Heth, Jason; Carter, Corey A; Oronsky, Arnold; Knox, Susan J; Caroen, Scott; Oronsky, Bryan; Scicinski, Jan; Lawrence, Theodore S; Lao, Christopher D

    2016-04-01

    Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases. Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial. Published by Elsevier Inc.

  17. White Matter Compromise of Callosal and Subcortical Fiber Tracts in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

    Science.gov (United States)

    Shukla, Dinesh K.; Keehn, Brandon; Lincoln, Alan J.; Muller, Ralph-Axel

    2010-01-01

    Objective: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle…

  18. Effect of increasing diffusion gradient direction number on diffusion tensor imaging fiber tracking in the human brain

    International Nuclear Information System (INIS)

    Yao, Xu Fang; Liang, Bie Bei; Xia, Tian; Huang, Qin Ming; Zhuang, Song Lin; Yu, Tong Gang

    2015-01-01

    To assess the effects of varying the number of diffusion gradient directions (NDGDs) on diffusion tensor fiber tracking (FT) in human brain white matter using tract characteristics. Twelve normal volunteers underwent diffusion tensor imaging (DTI) scanning with NDGDs of 6, 11, 15, 21, and 31 orientations. Three fiber tract groups, including the splenium of the corpus callosum (CC), the entire CC, and the full brain tract, were reconstructed by deterministic DTI-FT. Tract architecture was first qualitatively evaluated by visual observation. Six quantitative tract characteristics, including the number of fibers (NF), average length (AL), fractional anisotropy (FA), relative anisotropy (RA), mean diffusivity (MD), and volume ratio (VR) were measured for the splenium of the CC at the tract branch level, for the entire CC at tract level, and for the full brain tract at the whole brain level. Visual results and those of NF, AL, FA, RA, MD, and VR were compared among the five different NDGDs. The DTI-FT with NDGD of 11, 15, 21, and 31 orientations gave better tracking results compared with NDGD of 6 after the visual evaluation. NF, FA, RA, MD, and VR values with NDGD of six were significantly greater (smallest p = 0.001 to largest p = 0.042) than those with four other NDGDs (11, 15, 21, or 31 orientations), whereas AL measured with NDGD of six was significantly smaller (smallest p = 0.001 to largest p = 0.041) than with four other NDGDs (11, 15, 21, or 31 orientations). No significant differences were observed in the results among the four NDGD groups of 11, 15, 21, and 31 directions (smallest p = 0.059 to largest p = 1.000). The main fiber tracts were detected with NDGD of six orientations; however, the use of larger NDGD (> or = 11 orientations) could provide improved tract characteristics at the expense of longer scanning time.

  19. Effect of increasing diffusion gradient direction number on diffusion tensor imaging fiber tracking in the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Xu Fang; Liang, Bie Bei; Xia, Tian; Huang, Qin Ming; Zhuang, Song Lin [School of Optical-Electrical and Computer Engineering, Shanghai Medical Instrument College, University of Shanghai for Science and Technology, Shanghai (China); Yu, Tong Gang [Dept. of Radiology, Huashan Hospital, Fudan University, Shanghai (China)

    2015-04-15

    To assess the effects of varying the number of diffusion gradient directions (NDGDs) on diffusion tensor fiber tracking (FT) in human brain white matter using tract characteristics. Twelve normal volunteers underwent diffusion tensor imaging (DTI) scanning with NDGDs of 6, 11, 15, 21, and 31 orientations. Three fiber tract groups, including the splenium of the corpus callosum (CC), the entire CC, and the full brain tract, were reconstructed by deterministic DTI-FT. Tract architecture was first qualitatively evaluated by visual observation. Six quantitative tract characteristics, including the number of fibers (NF), average length (AL), fractional anisotropy (FA), relative anisotropy (RA), mean diffusivity (MD), and volume ratio (VR) were measured for the splenium of the CC at the tract branch level, for the entire CC at tract level, and for the full brain tract at the whole brain level. Visual results and those of NF, AL, FA, RA, MD, and VR were compared among the five different NDGDs. The DTI-FT with NDGD of 11, 15, 21, and 31 orientations gave better tracking results compared with NDGD of 6 after the visual evaluation. NF, FA, RA, MD, and VR values with NDGD of six were significantly greater (smallest p = 0.001 to largest p = 0.042) than those with four other NDGDs (11, 15, 21, or 31 orientations), whereas AL measured with NDGD of six was significantly smaller (smallest p = 0.001 to largest p = 0.041) than with four other NDGDs (11, 15, 21, or 31 orientations). No significant differences were observed in the results among the four NDGD groups of 11, 15, 21, and 31 directions (smallest p = 0.059 to largest p = 1.000). The main fiber tracts were detected with NDGD of six orientations; however, the use of larger NDGD (> or = 11 orientations) could provide improved tract characteristics at the expense of longer scanning time.

  20. Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3.

    Science.gov (United States)

    Uekawa, Ken; Nakamura, Hideo; Shinojima, Naoki; Takezaki, Tatsuya; Yano, Shigetoshi; Kuratsu, Jun-Ichi

    2016-04-01

    Unlike in children, brain stem gliomas in adult are rare and still poorly understood. In addition, most adult brain stem gliomas result predominantly in the pons and are less often found in the medulla oblongata. Here, we report a case of an adult glioma in the medulla oblongata and its molecular biological features. A 46-year-old male presented with gait disturbance, paresthesia, and dysphagia. Magnetic resonance imaging (MRI) showed a diffuse hyper-intensive lesion in the medulla oblongata on a T 2 -weighted image without gadolinium contrast enhancement. We performed an open biopsy and the lesion was pathologically diagnosed as a diffuse astrocytoma. Molecular biological analyses revealed the absence of histone H3.3 mutation (H3F3A K27M), and presence of methylation of O-6-methylguanine-DNA methyltransferase (MGMT) promoter and a mutation in isocitrate dehydrogenase 1 (IDH-1). The patient received local radiotherapy and temozolomide chemotherapy. The patient's symptoms were ameliorated, and MRI showed no tumor growth at 6 months after the initial treatment. Biopsy for brain stem lesions is generally thought to have risk of complications, but if performed minimally, it is useful to diagnose and determine treatment strategy. Obtaining patient characteristics and molecular biological features will provide insight towards therapeutic treatment for adult brain stem gliomas.

  1. Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pokhrel, Damodar, E-mail: dpokhrel@kumc.edu; Sood, Sumit; McClinton, Christopher; Shen, Xinglei; Lominska, Christopher; Saleh, Habeeb; Badkul, Rajeev; Jiang, Hongyu; Mitchell, Melissa; Wang, Fen

    2016-01-01

    Purpose: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). Materials and methods: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured on T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30 Gy for WB-PTV and 45 Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. Results: All 5 HS-WBRT with SIB plans met WB-PTV D{sub 2%}, D{sub 98%}, and V{sub 30} {sub Gy} NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5

  2. Treatment planning strategy for whole-brain radiotherapy with hippocampal sparing and simultaneous integrated boost for multiple brain metastases using intensity-modulated arc therapy

    International Nuclear Information System (INIS)

    Pokhrel, Damodar; Sood, Sumit; McClinton, Christopher; Shen, Xinglei; Lominska, Christopher; Saleh, Habeeb; Badkul, Rajeev; Jiang, Hongyu; Mitchell, Melissa; Wang, Fen

    2016-01-01

    Purpose: To retrospectively evaluate the accuracy, plan quality and efficiency of intensity-modulated arc therapy (IMAT) for hippocampal sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in patients with multiple brain metastases (m-BM). Materials and methods: A total of 5 patients with m-BM were retrospectively replanned for HS-WBRT with SIB using IMAT treatment planning. The hippocampus was contoured on diagnostic T1-weighted magnetic resonance imaging (MRI) which had been fused with the planning CT image set. The hippocampal avoidance zone (HAZ) was generated using a 5-mm uniform margin around the paired hippocampi. The m-BM planning target volumes (PTVs) were contoured on T1/T2-weighted MRI registered with the 3D planning computed tomography (CT). The whole-brain planning target volume (WB-PTV) was defined as the whole-brain tissue volume minus HAZ and m-BM PTVs. Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis-TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5-mm leaf width at isocenter) and 6-MV beam. Prescription dose was 30 Gy for WB-PTV and 45 Gy for each m-BM in 10 fractions. Three full coplanar arcs with orbit avoidance sectors were used. Treatment plans were evaluated using homogeneity (HI) and conformity indices (CI) for target coverage and dose to organs at risk (OAR). Dose delivery efficiency and accuracy of each IMAT plan was assessed via quality assurance (QA) with a MapCHECK device. Actual beam-on time was recorded and a gamma index was used to compare dose agreement between the planned and measured doses. Results: All 5 HS-WBRT with SIB plans met WB-PTV D 2% , D 98% , and V 30 Gy NRG-CC001 requirements. The plans demonstrated highly conformal and homogenous coverage of the WB-PTV with mean HI and CI values of 0.33 ± 0.04 (range: 0.27 to 0.36), and 0.96 ± 0.01 (range: 0.95 to 0.97), respectively. All 5 hippocampal sparing

  3. Multi-site study of diffusion metric variability: effects of site, vendor, field strength, and echo time on regions-of-interest and histogram-bin analyses.

    Science.gov (United States)

    Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

    2016-02-27

    It is now common for magnetic-resonance-imaging (MRI) based multi-site trials to include diffusion-weighted imaging (DWI) as part of the protocol. It is also common for these sites to possess MR scanners of different manufacturers, different software and hardware, and different software licenses. These differences mean that scanners may not be able to acquire data with the same number of gradient amplitude values and number of available gradient directions. Variability can also occur in achievable b-values and minimum echo times. The challenge of a multi-site study then, is to create a common protocol by understanding and then minimizing the effects of scanner variability and identifying reliable and accurate diffusion metrics. This study describes the effect of site, scanner vendor, field strength, and TE on two diffusion metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA) using two common analyses (region-of-interest and mean-bin value of whole brain histograms). The goal of the study was to identify sources of variability in diffusion-sensitized imaging and their influence on commonly reported metrics. The results demonstrate that the site, vendor, field strength, and echo time all contribute to variability in FA and MD, though to different extent. We conclude that characterization of the variability of DTI metrics due to site, vendor, field strength, and echo time is a worthwhile step in the construction of multi-center trials.

  4. Whole brain, high resolution multiband spin-echo EPI fMRI at 7 T: A comparison with gradient-echo EPI using a color-word Stroop task

    NARCIS (Netherlands)

    Boyacioglu, R.; Schulz, J.; Müller, N.C.J.; Koopmans, P.J.; Barth, M.; Norris, David Gordon

    2014-01-01

    A whole brain, multiband spin-echo (SE) echo planar imaging (EPI) sequence employing a high spatial (1.5 mm isotropic) and temporal (TR of 2 s) resolution was implemented at 7 T. Its overall performance (tSNR, sensitivity and CNR) was assessed and compared to a geometrically matched gradient-echo

  5. Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

    Science.gov (United States)

    Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

    2018-06-13

    To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

  6. Sorption of Sr, Co and Zn on illite: Batch experiments and modelling including Co in-diffusion measurements on compacted samples

    Science.gov (United States)

    Montoya, V.; Baeyens, B.; Glaus, M. A.; Kupcik, T.; Marques Fernandes, M.; Van Laer, L.; Bruggeman, C.; Maes, N.; Schäfer, T.

    2018-02-01

    Experimental investigations on the uptake of divalent cations (Sr, Co and Zn) onto illite (Illite du Puy, Le-Puy-en-Velay, France) were carried out by three different international research groups (Institute for Nuclear Waste Disposal, KIT (Germany), Group Waste & Disposal, SCK-CEN, (Belgium) and Laboratory for Waste Management, PSI (Switzerland)) in the framework of the European FP7 CatClay project. The dependence of solid-liquid distribution ratios (Rd values) on pH at trace metal conditions (sorption edges) and on the metal ion concentration (sorption isotherms) was determined in dilute suspensions of homo-ionic Na-illite (Na-IdP) under controlled N2 atmosphere. The experimental results were modelled using the 2 Site Protolysis Non Electrostatic Surface Complexation and Cation Exchange (2SPNE SC/CE) sorption model. The sorption of Sr depends strongly on ionic strength, while a rather weak pH dependence is observed in a pH range between 3 and 11. The data were modelled with cation exchange reactions, taking into account competition with H, K, Ca, Mg and Al, and surface complexation on weak amphotheric edge sites at higher pH values. The sorption of Co on Na-IdP, however, is strongly pH dependent. Cation exchange on the planar sites and surface complexation on strong and weak amphoteric edge sites were used to describe the Co sorption data. Rd values for Co derived from in-diffusion measurements on compacted Na-IdP samples (bulk-dry density of 1700 kg m-3) between pH 5.0 and 9.0 are in good agreement with the batch sorption data. The equivalence of both approaches to measure sorption was thus confirmed for the present test system. In addition, the results highlight the importance of both major and minor surface species for the diffusive transport behaviour of strongly sorbing metal cations. While surface complexes at the edge sites determine largely the Rd value, the diffusive flux may be governed by those species bound to the planar sites, even at low fractional

  7. SU-F-T-388: Comparison of Biophysical Indices in Hippocampal-Avoidance Whole Brain VMAT and IMRT Radiation Therapy Treatment Plans

    International Nuclear Information System (INIS)

    Kendall, E; Ahmad, S; Algan, O; Higby, C; Hossain, S

    2016-01-01

    Purpose: To compare biophysical indices of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) treatment plans for whole brain radiation therapy following the NRG-CC001 protocol. Methods: In this retrospective study, a total of fifteen patients were planned with Varian Eclipse Treatment Planning System using VMAT (RapidArc) and IMRT techniques. The planning target volume (PTV) was defined as the whole brain volume excluding a uniform three-dimensional 5mm expansion of the hippocampus volume. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 95% of the target volume receiving 100% of the prescribed dose. The NRG Oncology protocol guidelines were followed for contouring and dose-volume constraints. A single radiation oncologist evaluated all treatment plans. Calculations of statistical significance were performed using Student’s paired t-test. Results: All VMAT and IMRT plans met the NRG-CC001 protocol dose-volume criteria. The average equivalent uniform dose (EUD) for the PTV for VMAT vs. IMRT was respectively (19.05±0.33 Gy vs. 19.38±0.47 Gy) for α/β of 2 Gy and (19.47±0.30 Gy vs. 19.84±0.42 Gy) for α/β of 10 Gy. For the PTV, the average mean and maximum doses were 2% and 5% lower in VMAT plans than in IMRT plans, respectively. The average EUD and the normal tissue complication probability (NTCP) for the hippocampus in VMAT vs. IMRT plans were (15.28±1.35 Gy vs. 15.65±0.99 Gy, p=0.18) and (0.305±0.012 Gy vs. 0.308±0.008 Gy, p=0.192), respectively. The average EUD and NTCP for the optic chiasm were both 2% higher in VMAT than in IMRT plans. Conclusion: Though statistically insignificant, VMAT plans indicate a lower hippocampus EUD than IMRT plans. Also, a small variation in NTCP was found between plans.

  8. SU-F-T-388: Comparison of Biophysical Indices in Hippocampal-Avoidance Whole Brain VMAT and IMRT Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Kendall, E; Ahmad, S; Algan, O; Higby, C; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2016-06-15

    Purpose: To compare biophysical indices of Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT) treatment plans for whole brain radiation therapy following the NRG-CC001 protocol. Methods: In this retrospective study, a total of fifteen patients were planned with Varian Eclipse Treatment Planning System using VMAT (RapidArc) and IMRT techniques. The planning target volume (PTV) was defined as the whole brain volume excluding a uniform three-dimensional 5mm expansion of the hippocampus volume. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 95% of the target volume receiving 100% of the prescribed dose. The NRG Oncology protocol guidelines were followed for contouring and dose-volume constraints. A single radiation oncologist evaluated all treatment plans. Calculations of statistical significance were performed using Student’s paired t-test. Results: All VMAT and IMRT plans met the NRG-CC001 protocol dose-volume criteria. The average equivalent uniform dose (EUD) for the PTV for VMAT vs. IMRT was respectively (19.05±0.33 Gy vs. 19.38±0.47 Gy) for α/β of 2 Gy and (19.47±0.30 Gy vs. 19.84±0.42 Gy) for α/β of 10 Gy. For the PTV, the average mean and maximum doses were 2% and 5% lower in VMAT plans than in IMRT plans, respectively. The average EUD and the normal tissue complication probability (NTCP) for the hippocampus in VMAT vs. IMRT plans were (15.28±1.35 Gy vs. 15.65±0.99 Gy, p=0.18) and (0.305±0.012 Gy vs. 0.308±0.008 Gy, p=0.192), respectively. The average EUD and NTCP for the optic chiasm were both 2% higher in VMAT than in IMRT plans. Conclusion: Though statistically insignificant, VMAT plans indicate a lower hippocampus EUD than IMRT plans. Also, a small variation in NTCP was found between plans.

  9. Identifying the Alternation Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-brain Voxel-wise Degree Analysis

    Directory of Open Access Journals (Sweden)

    Yanjia Deng

    2016-08-01

    Full Text Available Patients with mild cognitive impairment (MCI are at high risk for developing Alzheimer’s disease (AD, while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI and stable MCI (SMCI individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alternation patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer’s Disease Neuroimaging Initiative dataset, and the progression was determined based on a three-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a severe presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective

  10. Voxel-based clustered imaging by multiparameter diffusion tensor images for glioma grading.

    Science.gov (United States)

    Inano, Rika; Oishi, Naoya; Kunieda, Takeharu; Arakawa, Yoshiki; Yamao, Yukihiro; Shibata, Sumiya; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu

    2014-01-01

    Gliomas are the most common intra-axial primary brain tumour; therefore, predicting glioma grade would influence therapeutic strategies. Although several methods based on single or multiple parameters from diagnostic images exist, a definitive method for pre-operatively determining glioma grade remains unknown. We aimed to develop an unsupervised method using multiple parameters from pre-operative diffusion tensor images for obtaining a clustered image that could enable visual grading of gliomas. Fourteen patients with low-grade gliomas and 19 with high-grade gliomas underwent diffusion tensor imaging and three-dimensional T1-weighted magnetic resonance imaging before tumour resection. Seven features including diffusion-weighted imaging, fractional anisotropy, first eigenvalue, second eigenvalue, third eigenvalue, mean diffusivity and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. We developed a two-level clustering approach for a self-organizing map followed by the K-means algorithm to enable unsupervised clustering of a large number of input vectors with the seven features for the whole brain. The vectors were grouped by the self-organizing map as protoclusters, which were classified into the smaller number of clusters by K-means to make a voxel-based diffusion tensor-based clustered image. Furthermore, we also determined if the diffusion tensor-based clustered image was really helpful for predicting pre-operative glioma grade in a supervised manner. The ratio of each class in the diffusion tensor-based clustered images was calculated from the regions of interest manually traced on the diffusion tensor imaging space, and the common logarithmic ratio scales were calculated. We then applied support vector machine as a classifier for distinguishing between low- and high-grade gliomas. Consequently, the sensitivity, specificity, accuracy and area under the curve of receiver operating characteristic

  11. Whole-brain functional connectivity during acquisition of novel grammar: Distinct functional networks depend on language learning abilities.

    Science.gov (United States)

    Kepinska, Olga; de Rover, Mischa; Caspers, Johanneke; Schiller, Niels O

    2017-03-01

    In an effort to advance the understanding of brain function and organisation accompanying second language learning, we investigate the neural substrates of novel grammar learning in a group of healthy adults, consisting of participants with high and average language analytical abilities (LAA). By means of an Independent Components Analysis, a data-driven approach to functional connectivity of the brain, the fMRI data collected during a grammar-learning task were decomposed into maps representing separate cognitive processes. These included the default mode, task-positive, working memory, visual, cerebellar and emotional networks. We further tested for differences within the components, representing individual differences between the High and Average LAA learners. We found high analytical abilities to be coupled with stronger contributions to the task-positive network from areas adjacent to bilateral Broca's region, stronger connectivity within the working memory network and within the emotional network. Average LAA participants displayed stronger engagement within the task-positive network from areas adjacent to the right-hemisphere homologue of Broca's region and typical to lower level processing (visual word recognition), and increased connectivity within the default mode network. The significance of each of the identified networks for the grammar learning process is presented next to a discussion on the established markers of inter-individual learners' differences. We conclude that in terms of functional connectivity, the engagement of brain's networks during grammar acquisition is coupled with one's language learning abilities. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

    2013-09-01

    Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P RPA class II/III patients.

  13. Decreased cerebellar-orbitofrontal connectivity correlates with stuttering severity: Whole-brain functional and structural connectivity associations with persistent developmental stuttering

    Directory of Open Access Journals (Sweden)

    Kevin Richard Sitek

    2016-05-01

    Full Text Available Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here, we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex. Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and orbitofrontal cortex may underlie successful compensatory mechanisms by more fluent stutterers.

  14. Hypofractionated stereotactic radiotherapy in five daily fractions for post-operative surgical cavities in brain metastases patients with and without prior whole brain radiation.

    Science.gov (United States)

    Al-Omair, Ameen; Soliman, Hany; Xu, Wei; Karotki, Aliaksandr; Mainprize, Todd; Phan, Nicolas; Das, Sunit; Keith, Julia; Yeung, Robert; Perry, James; Tsao, May; Sahgal, Arjun

    2013-12-01

    Our purpose was to report efficacy of hypofractionated cavity stereotactic radiotherapy (HCSRT) in patients with and without prior whole brain radiotherapy (WBRT). 32 surgical cavities in 30 patients (20 patients/21 cavities had no prior WBRT and 10 patients/11 cavities had prior WBRT) were treated with image-guided linac stereotactic radiotherapy. 7 of the 10 prior WBRT patients had "resistant" local disease given prior surgery, post-operative WBRT and a re-operation, followed by salvage HCSRT. The clinical target volume was the post-surgical cavity, and a 2-mm margin applied as planning target volume. The median total dose was 30 Gy (range: 25-37.5 Gy) in 5 fractions. In the no prior and prior WBRT cohorts, the median follow-up was 9.7 months (range: 3.0-23.6) and 15.3 months (range: 2.9-39.7), the median survival was 23.6 months and 39.7 months, and the 1-year cavity local recurrence progression- free survival (LRFS) was 79 and 100%, respectively. At 18 months the LRFS dropped to 29% in the prior WBRT cohort. Grade 3 radiation necrosis occurred in 3 prior WBRT patients. We report favorable outcomes with HCSRT, and well selected patients with prior WBRT and "resistant" disease may have an extended survival favoring aggressive salvage HCSRT at a moderate risk of radiation necrosis.

  15. External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

    Science.gov (United States)

    Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

    2017-07-01

    A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Increased brain iron deposition is a risk factor for brain atrophy in patients with haemodialysis: a combined study of quantitative susceptibility mapping and whole brain volume analysis.

    Science.gov (United States)

    Chai, Chao; Zhang, Mengjie; Long, Miaomiao; Chu, Zhiqiang; Wang, Tong; Wang, Lijun; Guo, Yu; Yan, Shuo; Haacke, E Mark; Shen, Wen; Xia, Shuang

    2015-08-01

    To explore the correlation between increased brain iron deposition and brain atrophy in patients with haemodialysis and their correlation with clinical biomarkers and neuropsychological test. Forty two patients with haemodialysis and forty one age- and gender-matched healthy controls were recruited in this prospective study. 3D whole brain high resolution T1WI and susceptibility weighted imaging were scanned on a 3 T MRI system. The brain volume was analyzed using voxel-based morphometry (VBM) in patients and to compare with that of healthy controls. Quantitative susceptibility mapping was used to measure and compare the susceptibility of different structures between patients and healthy controls. Correlation analysis was used to investigate the relationship between the brain volume, iron deposition and neuropsychological scores. Stepwise multiple regression analysis was used to explore the effect of clinical biomarkers on the brain volumes in patients. Compared with healthy controls, patients with haemodialysis showed decreased volume of bilateral putamen and left insular lobe (All P brain iron deposition is negatively correlated with the decreased volume of bilateral putamen (P brain iron deposition and dialysis duration was risk factors for brain atrophy in patients with haemodialysis. The decreased gray matter volume of the left insular lobe was correlated with neurocognitive impairment.

  17. Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering.

    Science.gov (United States)

    Sitek, Kevin R; Cai, Shanqing; Beal, Deryk S; Perkell, Joseph S; Guenther, Frank H; Ghosh, Satrajit S

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers.

  18. Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering

    Science.gov (United States)

    Sitek, Kevin R.; Cai, Shanqing; Beal, Deryk S.; Perkell, Joseph S.; Guenther, Frank H.; Ghosh, Satrajit S.

    2016-01-01

    Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers. PMID:27199712

  19. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival

    International Nuclear Information System (INIS)

    Stea, Baldassarre; Suh, John H.; Boyd, Adam P. M.S.; Cagnoni, Pablo J.; Shaw, Edward

    2006-01-01

    Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm

  20. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Rades, Dirk; Nadrowitz, Roger; Buchmann, Inga; Meller, Birgit; Hunold, Peter; Noack, Frank; Schild, Steven E.

    2010-01-01

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m 2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m 2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m 2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ( 123 I-Erbi) on scintigraphy; 123 I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  1. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk; Nadrowitz, Roger [Dept. of Radiation Oncology, Univ. of Luebeck (Germany); Buchmann, Inga; Meller, Birgit [Section of Nuclear Medicine, Univ. of Luebeck (Germany); Hunold, Peter [Dept. of Radiology, Univ. of Luebeck (Germany); Noack, Frank [Inst. of Pathology, Univ. of Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2010-08-15

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m{sup 2} cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m{sup 2} cetuximab (cold antibody) were given. Weekly doses of 250 mg/m{sup 2} cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ({sup 123}I-Erbi) on scintigraphy; {sup 123}I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  2. 320-Multidetector row whole-head dynamic subtracted CT angiography and whole-brain CT perfusion before and after carotid artery stenting: Technical note

    International Nuclear Information System (INIS)

    San Millan Ruiz, Diego; Murphy, Kieran; Gailloud, Philippe

    2010-01-01

    Introduction: Multidetector CT (MDCT) is increasingly used for the investigation of neurovascular disorders, but restricted z-axis coverage (3.2 cm for 64-MDCT) currently limits perfusion to a small portion of the brain close to the circle of Willis, and precludes dynamic angiographic appreciation of the entire brain circulation. We illustrate the clinical potential of recently developed 320-MDCT extending the z-axis coverage to 16 cm in a patient with symptomatic carotid artery stenosis. Methods: In a 74-year-old patient presenting with critical symptomatic stenosis of the left CCA, pre- and post-carotid artery stenting whole-head subtracted dynamic MDCT angiography and perfusion were obtained in addition to CT angiography of the supra-aortic trunks. Both whole-head subtracted MDCT angiography and perfusion demonstrated delayed left ICA circulation, which normalized after carotid stenting. Discussion: 320-MDCT offers unprecedented z-axis coverage allowing for whole-brain perfusion and subtracted dynamic angiography of the entire intracranial circulation. These innovations can consolidate the role of MDCT as a first intention imaging technique for cerebrovascular disorders, in particular for the acute management of stroke.

  3. Patterns of cortical oscillations organize neural activity into whole-brain functional networks evident in the fMRI BOLD signal

    Directory of Open Access Journals (Sweden)

    Jennifer C Whitman

    2013-03-01

    Full Text Available Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG / MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

  4. Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

    2009-01-01

    Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

  5. Functional Clustering of the Human Inferior Parietal Lobule by Whole-Brain Connectivity Mapping of Resting-State Functional Magnetic Resonance Imaging Signals

    Science.gov (United States)

    Li, Chiang-Shan R.

    2014-01-01

    Abstract The human inferior parietal lobule (IPL) comprised the lateral bank of the intraparietal sulcus, angular gyrus, and supramarginal gyrus, defined on the basis of anatomical landmarks and cytoarchitectural organization of neurons. However, it is not clear as to whether the three areas represent functional subregions within the IPL. For instance, imaging studies frequently identified clusters of activities that cut across areal boundaries. Here, we used resting-state functional magnetic resonance imaging (fMRI) data to examine how individual voxels within the IPL are best clustered according to their connectivity to the whole brain. The results identified a best estimate of seven clusters that are hierarchically arranged as the anterior, middle, and posterior subregions. The anterior, middle, and posterior IPL are each significantly connected to the somatomotor areas, superior/middle/inferior frontal gyri, and regions of the default mode network. This functional segregation is supported by recent cytoarchitechtonics and tractography studies. IPL showed hemispheric differences in connectivity that accord with a predominantly left parietal role in tool use and language processing and a right parietal role in spatial attention and mathematical cognition. The functional clusters may also provide a more parsimonious and perhaps even accurate account of regional activations of the IPL during a variety of cognitive challenges, as reported in earlier fMRI studies. PMID:24308753

  6. Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage

    International Nuclear Information System (INIS)

    Fu, Jun; Chen, Wei-jian; Wang, Mei-hao; Li, Jian-ce; Zhang, Qian; Xia, Neng-zhi; Yang, Yun-jun; Wu, Gui-yun; Cheng, Jing-liang; Zhang, Yong; Zhuge, Qichuan

    2015-01-01

    The purpose of this study was to evaluate the value of 320-detector row CT used to detect crossed cerebellar diaschisis (CCD) in patients with unilateral supratentorial spontaneous intracerebral hemorrhage (SICH). We investigated 62 of 156 patients with unilateral supratentorial SICH using 320-detector row CT scanning. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), and time to peak (rTTP) levels were measured in different regions of interest (ROIs) that were manually outlined on computed tomography perfusion (CTP) for the cerebrum, including normal-appearing brain tissue that surrounded the perilesional low-density area (NA) and the perihematomal low-density area (PA) in all patients and the cerebellum (ipsilateral and contralateral) in CCD-positive patients. Of 62 cases, a total of 14 met the criteria for CCD due to cerebellar perfusion asymmetry on CTP maps. In the quantitative analysis, significant differences were found in the perfusion parameters between the contralateral and ipsilateral cerebellum in CCD-positive cases. No significant differences were found between the CCD-positive group and the CCD-negative group according to the hematoma volume, NIHSS scores, and cerebral perfusion abnormality (each P > 0.05). The correlation analysis of the degree of NA, PA perfusion abnormality, and the degree of CCD severity showed negative and significant linear correlations (R, -0.66∝-0.56; P < 0.05). 320-detector row CT is a robust and practicable method for the comprehensive primary imaging work-up of CCD in unilateral supratentorial SICH patients. (orig.)

  7. Prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results

    International Nuclear Information System (INIS)

    Packer, R.J.; Sutton, L.N.; Atkins, T.E.; Radcliffe, J.; Bunin, G.R.; D'Angio, G.; Siegel, K.R.; Schut, L.

    1989-01-01

    As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties

  8. Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jun; Chen, Wei-jian; Wang, Mei-hao; Li, Jian-ce; Zhang, Qian; Xia, Neng-zhi; Yang, Yun-jun [Wenzhou Medical University, Department of Radiology, First Affiliated Hospital, Wenzhou (China); Wu, Gui-yun [Cleveland Clinics Foundation, Department of Nuclear Medicine, Imaging Institute, Cleveland, OH (United States); Cheng, Jing-liang; Zhang, Yong [Zhengzhou University, Department of Radiology, First Affiliated Hospital, Zhengzhou (China); Zhuge, Qichuan [Wenzhou Medical University, Department of Neurosurgery, First Affiliated Hospital, Wenzhou (China)

    2014-11-09

    The purpose of this study was to evaluate the value of 320-detector row CT used to detect crossed cerebellar diaschisis (CCD) in patients with unilateral supratentorial spontaneous intracerebral hemorrhage (SICH). We investigated 62 of 156 patients with unilateral supratentorial SICH using 320-detector row CT scanning. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), and time to peak (rTTP) levels were measured in different regions of interest (ROIs) that were manually outlined on computed tomography perfusion (CTP) for the cerebrum, including normal-appearing brain tissue that surrounded the perilesional low-density area (NA) and the perihematomal low-density area (PA) in all patients and the cerebellum (ipsilateral and contralateral) in CCD-positive patients. Of 62 cases, a total of 14 met the criteria for CCD due to cerebellar perfusion asymmetry on CTP maps. In the quantitative analysis, significant differences were found in the perfusion parameters between the contralateral and ipsilateral cerebellum in CCD-positive cases. No significant differences were found between the CCD-positive group and the CCD-negative group according to the hematoma volume, NIHSS scores, and cerebral perfusion abnormality (each P > 0.05). The correlation analysis of the degree of NA, PA perfusion abnormality, and the degree of CCD severity showed negative and significant linear correlations (R, -0.66∝-0.56; P < 0.05). 320-detector row CT is a robust and practicable method for the comprehensive primary imaging work-up of CCD in unilateral supratentorial SICH patients. (orig.)

  9. Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

    International Nuclear Information System (INIS)

    Mehta, Minesh P.; Shapiro, William R.; Phan, See C.; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A.; Glantz, Michael J.; Recht, Lawrence; Langer, Corey; Sur, Ranjan K.; Roa, Wilson H.; Mahe, Marc A.; Fortin, Andre; Nieder, Carsten; Meyers, Christina A.; Smith, Jennifer A.; Miller, Richard A.; Renschler, Markus F.

    2009-01-01

    Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable

  10. Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

    Science.gov (United States)

    Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

    2009-02-01

    Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

  11. Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance

    Science.gov (United States)

    Helmer, K. G.; Chou, M-C.; Preciado, R. I.; Gimi, B.; Rollins, N. K.; Song, A.; Turner, J.; Mori, S.

    2016-01-01

    MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables. PMID:27350723

  12. Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance.

    Science.gov (United States)

    Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

    2016-02-27

    MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables.

  13. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Fan, Yun; Huang, Zhiyu; Fang, Luo; Miao, Lulu; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Lei, Tao; Mao, Weimin

    2015-09-01

    Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5-16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1%, respectively. No patient experienced ≥grade 4 toxicity. Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

  14. A whole brain volumetric approach in overweight/obese children: Examining the association with different physical fitness components and academic performance. The ActiveBrains project.

    Science.gov (United States)

    Esteban-Cornejo, Irene; Cadenas-Sanchez, Cristina; Contreras-Rodriguez, Oren; Verdejo-Roman, Juan; Mora-Gonzalez, Jose; Migueles, Jairo H; Henriksson, Pontus; Davis, Catherine L; Verdejo-Garcia, Antonio; Catena, Andrés; Ortega, Francisco B

    2017-10-01

    Obesity, as compared to normal weight, is associated with detectable structural differences in the brain. To the best of our knowledge, no previous study has examined the association of physical fitness with gray matter volume in overweight/obese children using whole brain analyses. Thus, the aim of this study was to examine the association between the key components of physical fitness (i.e. cardiorespiratory fitness, speed-agility and muscular fitness) and brain structural volume, and to assess whether fitness-related changes in brain volumes are related to academic performance in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited from Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 T S Magnetom Tim Trio system. Gray matter tissue was calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). Academic performance was assessed by the Batería III Woodcock-Muñoz Tests of Achievement. All analyses were controlled for sex, peak high velocity offset, parent education, body mass index and total brain volume. The statistical threshold was calculated with AlphaSim and further Hayasaka adjusted to account for the non-isotropic smoothness of structural images. The main results showed that higher cardiorespiratory fitness was related to greater gray matter volumes (P structures; besides, some of these brain structures may be related to better academic performance. Importantly, the identified associations of fitness and gray matter volume were different for each fitness component. These findings suggest that increases in cardiorespiratory fitness and speed-agility may positively influence the development of distinctive brain regions and academic indicators, and thus counteract the harmful effect of overweight and obesity on brain structure during childhood. Copyright

  15. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk [University Hospital Schleswig-Holstein, Luebeck (Germany). Department of Radiation Oncology]|[University Medical Center, Hamburg (Germany). Department of Radiation Oncology; Kueter, Jan-Dirk; Dunst, Juergen [University Hospital Schleswig-Holstein, Luebeck (Germany). Department of Radiation Oncology; Hornung, Dagmar [University Medical Center, Hamburg (Germany). Department of Radiation Oncology; Veninga, Theo; Hanssens, Patrick [Dr. Bernard Verbeeten Institute, Tilburg (Netherlands). Department of Radiation Oncology; Schild, Steven E. [Mayo Clinic Scottsdale, AZ (United States). Department of Radiation Oncology

    2008-12-15

    The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT + SRS). Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n = 93) or WBRT + SRS (n = 51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. 1-year-OS was 53% after SRS and 56% after WBRT + SRS (p = 0.24). 1-year-IC rates were 51% and 66% (p = 0.015), respectively. 1-year-LC rates were 66% and 87% (p = 0.003), respectively. On multivariate analyses, OS was associated with age (p = 0.004), ECOG-PS (p = 0.005), extracerebral metastases (p < 0.001), RPA class (p < 0.001), and interval from tumor diagnosis to irradiation (p < 0.001). IC was associated with interval from tumor diagnosis to irradiation (p = 0.004) and almost with treatment (p = 0.09), and LC with treatment (p = 0.026) and almost with interval (p = 0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. WBRT + SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients. (orig.)

  16. Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT + SRS) for one to three brain metastases

    International Nuclear Information System (INIS)

    Rades, Dirk; University Medical Center, Hamburg; Kueter, Jan-Dirk; Dunst, Juergen; Hornung, Dagmar; Veninga, Theo; Hanssens, Patrick; Schild, Steven E.

    2008-01-01

    The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT + SRS). Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n = 93) or WBRT + SRS (n = 51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. 1-year-OS was 53% after SRS and 56% after WBRT + SRS (p = 0.24). 1-year-IC rates were 51% and 66% (p = 0.015), respectively. 1-year-LC rates were 66% and 87% (p = 0.003), respectively. On multivariate analyses, OS was associated with age (p = 0.004), ECOG-PS (p = 0.005), extracerebral metastases (p < 0.001), RPA class (p < 0.001), and interval from tumor diagnosis to irradiation (p < 0.001). IC was associated with interval from tumor diagnosis to irradiation (p = 0.004) and almost with treatment (p = 0.09), and LC with treatment (p = 0.026) and almost with interval (p = 0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. WBRT + SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients. (orig.)

  17. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

    2012-01-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

  18. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    Science.gov (United States)

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.

    Science.gov (United States)

    Eylers, V V; Maudsley, A A; Bronzlik, P; Dellani, P R; Lanfermann, H; Ding, X-Q

    2016-03-01

    Knowledge of age-related physiological changes in the human brain is a prerequisite to identify neurodegenerative diseases. Therefore, in this study whole-brain (1)H-MRS was used in combination with quantitative MR imaging to study the effects of normal aging on healthy human brain metabolites and microstructure. Sixty healthy volunteers, 21-70 years of age, were studied. Brain maps of the metabolites NAA, creatine and phosphocreatine, and Cho and the tissue irreversible and reversible transverse relaxation times T2 and T2' were derived from the datasets. The relative metabolite concentrations and the values of relaxation times were measured with ROIs placed within the frontal and parietal WM, centrum semiovale, splenium of the corpus callosum, hand motor area, occipital GM, putamen, thalamus, pons ventral/dorsal, and cerebellar white matter and posterior lobe. Linear regression analysis and Pearson correlation tests were used to analyze the data. Aging resulted in decreased NAA concentrations in the occipital GM, putamen, splenium of the corpus callosum, and pons ventral and decreased creatine and phosphocreatine concentrations in the pons dorsal and putamen. Cho concentrations did not change significantly in selected brain regions. T2 increased in the cerebellar white matter and decreased in the splenium of the corpus callosum with aging, while the T2' decreased in the occipital GM, hand motor area, and putamen, and increased in the splenium of the corpus callosum. Correlations were found between NAA concentrations and T2' in the occipital GM and putamen and between creatine and phosphocreatine concentrations and T2' in the putamen. The effects of normal aging on brain metabolites and microstructure are region-dependent. Correlations between both processes are evident in the gray matter. The obtained data could be used as references for future studies on patients. © 2016 by American Journal of Neuroradiology.

  20. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Ming-Xiong Huang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz that can be measured and localized by resting-state magnetoencephalography (MEG. In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes, our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes, blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

  1. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    International Nuclear Information System (INIS)

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

    2014-01-01

    Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

  2. Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

    International Nuclear Information System (INIS)

    Shibamoto, Yuta; Baba, Fumiya; Oda, Kyota; Hayashi, Shinya; Kokubo, Masaki; Ishihara, Shun-Ichi; Itoh, Yoshiyuki; Ogino, Hiroyuki; Koizumi, Masahiko

    2008-01-01

    Purpose: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. Methods and Materials: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. Results: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 ± 0.39 (SD) at 6 months and 1.32 ± 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. Conclusions: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent

  3. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  4. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye, E-mail: dryetian@hotmail.com

    2014-01-10

    Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

  5. The AT1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation-Induced Cognitive Impairment

    International Nuclear Information System (INIS)

    Robbins, Mike E.; Payne, Valerie B.S.; Tommasi, Ellen B.S.; Diz, Debra I.; Hsu, Fang-Chi; Brown, William R.; Wheeler, Kenneth T.; Olson, John; Zhao Weiling

    2009-01-01

    Purpose: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Materials and Methods: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of γ rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Results: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Conclusions: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients

  6. Lymphopenia: A new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma

    International Nuclear Information System (INIS)

    Claude, Line; Perol, David; Ray-Coquard, Isabelle; Petit, Thierry; Blay, Jean-Yves; Carrie, Christian; Bachelot, Thomas

    2005-01-01

    Background and purpose: To determine overall survival (OS) and independent prognostic factors in patients with brain metastases (BM) from breast cancer treated by whole brain radiotherapy (WBR). Patients and methods: One hundred and twenty (120) women with BM, treated in a single French cancer center between 02/91 and 06/01, were reviewed. BM were confirmed by computed tomography or magnetic resonance imaging. Survival time was defined as the time interval from the date of BM to the date of death or last follow-up. A Cox proportional hazards regression model was used to determine significant prognostic factors in a multivariate analysis. Results: Surgery was followed by WBR in 5 patients. One hundred and four (104) patients received exclusive WBR, eight received concomitant chemo-radiation, and one received chemo-radiation after surgery. The median survival time was 5 months (95% CI: 3-7 months). In the multivariate analysis, performance status over 1 and lymphopenia (<0.7 G/L) were found to be independent prognostic factors for poor survival. Based on the number of these independent prognostic factors, we propose a predictive model for survival in brain metastatic cancer patients. Median survival was 7 months for patients presenting none or one poor prognosis factor at diagnosis versus 2 months for patients with 2 poor prognosis factors (p<0.0001) Conclusion: Brain metastases from breast cancer remain associated with very poor prognosis and there is a need for better treatment procedures. If confirmed in predictive models, the identification of prognostic subgroups, based on KPS and lymphopenia, among patients with BM from breast cancer would help physicians select patients for future clinical trials

  7. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  8. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Sunit [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Lovato, James F. [Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina (United States); Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P. [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States)

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

  9. NASA/DOD Aerospace Knowledge Diffusion Research Project. Report 10: Summary report to phase 3 academic library respondents including frequency distributions

    Science.gov (United States)

    Pinelli, Thomas E.; Kennedy, John M.; White, Terry F.

    1991-01-01

    Phase 3 of a 4 part study was undertaken to study the use of scientific and technical information (STI) in the academic aerospace community. Phase 3 of this project used three questionnaires that were sent to three groups (i.e., faculty, librarians, and students) in the academic aerospace community. Specific attention was paid to the types of STI used and the methods in which academic users acquire STI. The responses of the academic libraries are focussed on herein. Demographic information on academic aerospace libraries is provided. Data regarding NASA interaction with academic aerospace libraries is also included, as is the survey instrument.

  10. Diffusion-weighted imaging and cognition in the leukoariosis and disability in the elderly study

    DEFF Research Database (Denmark)

    Schmidt, Reinhold; Ropele, Stefan; Ferro, José

    2010-01-01

    : Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance......BACKGROUND AND PURPOSE: The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent...... without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions. RESULTS...

  11. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial

    OpenAIRE

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl

    2016-01-01

    Summary Background Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. Methods The Quality of Life a...

  12. Whole-brain vascular reactivity measured by fMRI using hyperventilation and breath-holding tasks: efficacy of 3D prospective acquisition correction (3D-PACE) for head motion

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Koshikawa, Tokiko; Fukatsu, Hiroshi; Ishigaki, Takeo; Maruyama, Katsuya; Takizawa, Osamu

    2004-01-01

    Functional MR imaging (fMRI) study using hyperventilation and breath-holding task has been reported to be one of the non-invasive methods to examine whole-brain vascular reactivity. The purpose of this study was to evaluate the efficacy of a method for 3D prospective detection and correction of head motion (3D-PACE) in a study of whole-brain vascular reactivity using hyperventilation and breath-holding tasks. Eight healthy volunteers were scanned using an fMRI protocol of hyperventilation and breath-holding task blocks at 3 T in separate runs with and without 3D-PACE. In two subjects, two more runs with and without 3D-PACE were repeated. The mean total number of activated voxels ± standard deviation was 26,405.3±1,822.2 in the run with 3D-PACE and 17,329.9±2,766.3 in the run without 3D-PACE (P<0.05), although there is some intersubject variation regarding the effect of 3D-PACE. In the two subjects whose performed two more runs, the number of activated voxels were smaller in the run without 3D-PACE than even in the run with 3D-PACE performed later. We conclude that 3D-PACE is beneficial for fMRI studies of whole-brain vascular reactivity induced by hyperventilation and breath-holding. (orig.)

  13. Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases

    International Nuclear Information System (INIS)

    Rojas-Puentes, Luis L; Gonzalez-Pinedo, Marcelino; Crismatt, Alejando; Ortega-Gomez, Alette; Gamboa-Vignolle, Carlos; Nuñez-Gomez, Rodrigo; Dorantes-Gallareta, Yusmiren; Arce-Salinas, Claudia; Arrieta, Oscar

    2013-01-01

    Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) before beginning radiotherapy and one month later. The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings

  14. Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP)

    International Nuclear Information System (INIS)

    Rades, D.; Bohlen, G.; Dunst, J.; Lohynska, R.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.

    2007-01-01

    Background: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Patients and Methods: Data regarding 101 CUP patients who received either short course WBRT (n = 34) with 5 x 4 Gy or long-course WBRT (n = 67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. Results: On univariate analysis, the radiation program was not associated with survival (p = 0.88) nor intracerebral control (p = 0.36). Improved survival was associated with KPS ≥ 70 (p < 0.001), absence of extracranial metastases (p < 0.001), and RPA-class 1 (p < 0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p < 0.001), extracranial metastases (RR: 1.70; p = 0.018), and RPA-class (RR: 2.86; p < 0.001) maintained significance. On univariate analysis, KPS (p < 0.001) and RPA-class (p < 0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p < 0.001) and RPA-class (RR: 2.09; p < 0.001) remained significant. Conclusion: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients. (orig.)

  15. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Aoyama, Hidefumi [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Kocher, Martin [Department of Radiation Oncology, University of Cologne, Cologne (Germany); Neupane, Binod [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Collette, Sandra [Statistics Department, European Organisation for Research and Treatment of Cancer, Brussels (Belgium); Tago, Masao [Department of Radiology, Teikyo University Mizonokuchi Hospital, Kanagawa (Japan); Shaw, Prakesh [Department of Pediatrics, Mount Sinai Hospital, Institute of Health Policy Management and Evaluation, University of Toronto, Ontario (Canada); Beyene, Joseph [Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario (Canada); Chang, Eric L. [Department of Radiation Oncology, University of Southern California, Los Angeles, California (United States); Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States)

    2015-03-15

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

  16. A whole-brain gray and white matter analysis in children with 45XO karyotype Turner syndrome: voxel-based morphometry

    International Nuclear Information System (INIS)

    Zhao Qiuling; Zhang Zhixin; Cheng Pangui; Xie Sheng; Liu Xiwei; Pan Hui; Li Kang; Zhang Jiaying; Gong Gaolang

    2013-01-01

    Objective: To detect the structural changes of cerebral gray and white matter in children of monosomy Turner syndrome (TS) by using voxel-based morphometry (VBM). Methods: Nine children 45XO karyotype TS and 20 age-matched control girls were recruited in this study. Wechsler intelligence scale for children was used to obtain their intelligence quotients (IQ). High-resolution magnetic MR imaging was performed in TS children and control girls to collect the whole brain structural data. The data were analyzed by VBM based on SPM 8 to compare the volume of gray and white matter between the TS children and normal controls by using covariance analysis. Results: The IQ of TS children was 81 ± 13, and the IQ of the controls was 109 ± 16. Statistical analysis revealed significant difference of IQ between the two groups (t = -4.70, P < 0.05). Compared with normal controls, TS children showed significantly decreased volume (numbers of voxel in clusters were 631, 525, 520, t = 3.95, 3.50, 3.36, P < 0.05, FWE-corrected) in the gray matter of the right superior parietal lobule, postcentral gyrus, precuneus lobule, calcarine, cuneus cortices, as well as the left middle and inferior occipital lobe. However, the volume of the bilateral supplemental motor area and the medial superior frontal lobes, the right middle cingulum, the left superior, middle, and inferior temporal gyri were increased in the TS children compared to the controls. The left fusiform, the left parahippocampus, the left hippocampus and the left cerebellum were also enlarged in TS children (numbers of voxel in clusters were 2082, 974, 1708, 588, 579, t = 5.45, 4.59, 4.40, 4.29, 3.55, P < 0.05, FWE-corrected). White matter regions in the left postcentral gyrus and inferior parietal lobule showed significantly reduced volume (voxel number 957, t = 5.85, P < 0.05, FWE-corrected). Conclusion: Children with monosomy TS show abnormal gray and white matter volumes in some brain regions, which may be involved in the

  17. Helical Tomotherapy for Whole-Brain Irradiation With Integrated Boost to Multiple Brain Metastases: Evaluation of Dose Distribution Characteristics and Comparison With Alternative Techniques

    International Nuclear Information System (INIS)

    Levegrün, Sabine; Pöttgen, Christoph; Wittig, Andrea; Lübcke, Wolfgang; Abu Jawad, Jehad; Stuschke, Martin

    2013-01-01

    Purpose: To quantitatively evaluate dose distribution characteristics achieved with helical tomotherapy (HT) for whole-brain irradiation (WBRT) with integrated boost (IB) to multiple brain metastases in comparison with alternative techniques. Methods and Materials: Dose distributions for 23 patients with 81 metastases treated with WBRT (30 Gy/10 fractions) and IB (50 Gy) were analyzed. The median number of metastases per patient (N mets ) was 3 (range, 2-8). Mean values of the composite planning target volume of all metastases per patient (PTV mets ) and of the individual metastasis planning target volume (PTV ind met ) were 8.7 ± 8.9 cm 3 (range, 1.3-35.5 cm 3 ) and 2.5 ± 4.5 cm 3 (range, 0.19-24.7 cm 3 ), respectively. Dose distributions in PTV mets and PTV ind met were evaluated with respect to dose conformity (conformation number [CN], RTOG conformity index [PITV]), target coverage (TC), and homogeneity (homogeneity index [HI], ratio of maximum dose to prescription dose [MDPD]). The dependence of dose conformity on target size and N mets was investigated. The dose distribution characteristics were benchmarked against alternative irradiation techniques identified in a systematic literature review. Results: Mean ± standard deviation of dose distribution characteristics derived for PTV mets amounted to CN = 0.790 ± 0.101, PITV = 1.161 ± 0.154, TC = 0.95 ± 0.01, HI = 0.142 ± 0.022, and MDPD = 1.147 ± 0.029, respectively, demonstrating high dose conformity with acceptable homogeneity. Corresponding numbers for PTV ind met were CN = 0.708 ± 0.128, PITV = 1.174 ± 0.237, TC = 0.90 ± 0.10, HI = 0.140 ± 0.027, and MDPD = 1.129 ± 0.030, respectively. The target size had a statistically significant influence on dose conformity to PTV mets (CN = 0.737 for PTV mets ≤4.32 cm 3 vs CN = 0.848 for PTV mets >4.32 cm 3 , P=.006), in contrast to N mets . The achieved dose conformity to PTV mets , assessed by both CN and PITV, was in all investigated volume strata

  18. SU-F-T-539: Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Radiation Therapy Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Kendall, E; Higby, C; Algan, O; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2016-06-15

    Purpose: To compare the treatment plan quality and dose gradient near the hippocampus between VMAT (RapidArc) and IMRT delivery techniques for whole brain radiation therapy. Methods: Fifteen patients were evaluated in this retrospective study. All treatments were planned on Varian Eclipse TPS, using 3-Arc VMAT and 9-Field IMRT, following NRG Oncology protocol NRG-CC001 guidelines evaluated by a single radiation oncologist. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 100% of the dose covering 95% of the target volume. Identical contour sets and dose-volume constraints following protocol guidelines were also applied in all plans. A paired t-test analysis was used to compare VMAT and IMRT plans. Results: NRG-CC001 protocol dose-volume constraints were met for all VMAT and IMRT plans. For the planning target volume (PTV), the average values for D2% and D98% were 6% lower and 4% higher in VMAT than in IMRT, respectively. The average mean and maximum hippocampus doses in Gy for VMAT vs IMRT plans were (11.85±0.81 vs. 12.24±0.56, p=0.10) and (16.27±0.78 vs. 16.59±0.71, p=0.24), respectively. In VMAT, the average mean and maximum chiasm doses were 3% and 1% higher than in IMRT plans, respectively. For the left optic nerve, the average mean and maximum doses were 10% and 5% higher in VMAT than in IMRT plans, respectively. These values were 12% and 3% for the right optic nerve. The average percentage of dose gradient around the hippocampus in the 0–5mm and 5–10mm abutted regions for VMAT vs. IMRT were (4.42%±2.22% /mm vs. 3.95%±2.61% /mm, p=0.43) and (4.54%±1.50% /mm vs. 4.39%±1.28% /mm, p=0.73), respectively. Conclusion: VMAT plans can achieve higher hippocampus sparing with a faster dose fall-off than IMRT plans. Though statistically insignificant, VMAT offers better PTV coverage with slightly higher doses to OARs.

  19. SU-F-T-539: Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Whole Brain Hippocampal Sparing Radiation Therapy Treatments

    International Nuclear Information System (INIS)

    Kendall, E; Higby, C; Algan, O; Ahmad, S; Hossain, S

    2016-01-01

    Purpose: To compare the treatment plan quality and dose gradient near the hippocampus between VMAT (RapidArc) and IMRT delivery techniques for whole brain radiation therapy. Methods: Fifteen patients were evaluated in this retrospective study. All treatments were planned on Varian Eclipse TPS, using 3-Arc VMAT and 9-Field IMRT, following NRG Oncology protocol NRG-CC001 guidelines evaluated by a single radiation oncologist. Prescribed doses in all plans were 30 Gy delivered over 10 fractions normalized to a minimum of 100% of the dose covering 95% of the target volume. Identical contour sets and dose-volume constraints following protocol guidelines were also applied in all plans. A paired t-test analysis was used to compare VMAT and IMRT plans. Results: NRG-CC001 protocol dose-volume constraints were met for all VMAT and IMRT plans. For the planning target volume (PTV), the average values for D2% and D98% were 6% lower and 4% higher in VMAT than in IMRT, respectively. The average mean and maximum hippocampus doses in Gy for VMAT vs IMRT plans were (11.85±0.81 vs. 12.24±0.56, p=0.10) and (16.27±0.78 vs. 16.59±0.71, p=0.24), respectively. In VMAT, the average mean and maximum chiasm doses were 3% and 1% higher than in IMRT plans, respectively. For the left optic nerve, the average mean and maximum doses were 10% and 5% higher in VMAT than in IMRT plans, respectively. These values were 12% and 3% for the right optic nerve. The average percentage of dose gradient around the hippocampus in the 0–5mm and 5–10mm abutted regions for VMAT vs. IMRT were (4.42%±2.22% /mm vs. 3.95%±2.61% /mm, p=0.43) and (4.54%±1.50% /mm vs. 4.39%±1.28% /mm, p=0.73), respectively. Conclusion: VMAT plans can achieve higher hippocampus sparing with a faster dose fall-off than IMRT plans. Though statistically insignificant, VMAT offers better PTV coverage with slightly higher doses to OARs.

  20. Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

    International Nuclear Information System (INIS)

    Sahgal, Arjun; Aoyama, Hidefumi; Kocher, Martin; Neupane, Binod; Collette, Sandra; Tago, Masao; Shaw, Prakesh; Beyene, Joseph; Chang, Eric L.

    2015-01-01

    Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group

  1. The diagnostic value of high-frequency power-based diffusion-weighted imaging in prediction of neuroepithelial tumour grading

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhiye; Liu, Mengqi [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Hainan Branch of Chinese PLA General Hospital, Department of Radiology, Sanya (China); Zhou, Peng [Chinese Academy of Sciences, Research Center for Brain-inspired Intelligence, Institute of Automation, Beijing (China); University of Chinese Academy of Sciences, Beijing (China); Lv, Bin [Academy of Telecommunication Research of MIIT, Beijing (China); Wang, Yan; Wang, Yulin; Lou, Xin; Ma, Lin [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Gui, Qiuping [Chinese PLA General Hospital, Department of Pathology, Beijing (China); He, Huiguang [Chinese Academy of Sciences, Research Center for Brain-inspired Intelligence, Institute of Automation, Beijing (China); University of Chinese Academy of Sciences, Beijing (China); Chinese Academy of Sciences, Center for Excellence in Brain Science and Intelligence Technology, Beijing (China)

    2017-12-15

    To retrospectively evaluate the diagnostic value of high-frequency power (HFP) compared with the minimum apparent diffusion coefficient (MinADC) in the prediction of neuroepithelial tumour grading. Diffusion-weighted imaging (DWI) data were acquired on 115 patients by a 3.0-T MRI system, which included b0 images and b1000 images over the whole brain in each patient. The HFP values and MinADC values were calculated by an in-house script written on the MATLAB platform. There was a significant difference among each group excluding grade I (G1) vs. grade II (G2) (P = 0.309) for HFP and among each group for MinADC. ROC analysis showed a higher discriminative accuracy between low-grade glioma (LGG) and high-grade glioma (HGG) for HFP with area under the curve (AUC) value 1 compared with that for MinADC with AUC 0.83 ± 0.04 and also demonstrated a higher discriminative ability among the G1-grade IV (G4) group for HFP compared with that for MinADC except G1 vs. G2. HFP could provide a simple and effective optimal tool for the prediction of neuroepithelial tumour grading based on diffusion-weighted images in routine clinical practice. (orig.)

  2. Quantitative diffusion characteristics of the human brain depend on MRI sequence parameters

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, M.; Blumhardt, L.D. [University of Nottingham, Department of Neurology, Royal Preston Hospital, Preston (United Kingdom); Morgan, P.S. [Division of Academic Radiology, Queens Medical Centre, Nottingham (United Kingdom)

    2002-07-01

    Quantitative diffusion-weighted MRI has been applied to the study of neurological diseases, including multiple sclerosis, where the molecular self-diffusion coefficient D has been measured in both lesions and normal-appearing white matter. Histograms of D have been used as a novel measure of the ''lesion load'', with potential applications that include the monitoring of efficacy in new treatment trials. However different ways of measuring D may affect its value, making comparison between different centres and research groups impossible. We aimed to assess the effect, if any, of using two different MRI sequences on the value of D. We studied 13 healthy volunteers, using two different quantitative diffusion sequences (including different b{sub max} values and gradient applications). Maps of D were analysed using both regions of interest (ROI) in white matter and ''whole brain'' histograms, and compared between the two sequences. In addition, we studied three standardised test liquids (with known values of D) using both sequences. Histograms from the two sequences had different distributions, with a greater spread and higher peak position from the sequence with lower b{sub max}. This greater spread of D was also evident in the white matter and test liquid ROI. ''Limits of agreement'' analysis demonstrated that the differences could be clinically relevant, despite significant correlations between the sequences obtained using simple rank methods. We conclude that different quantitative diffusion sequences are unlikely to produce directly comparable values of D, particularly if different b{sub max} values are used. In addition, the use of inappropriate statistical tests may give false impressions of close agreement. Standardisation of methods for the measurement of D are required if these techniques are to become useful tools, for example in monitoring changes in the disease burden of multiple sclerosis. (orig.)

  3. Quantitative diffusion characteristics of the human brain depend on MRI sequence parameters

    International Nuclear Information System (INIS)

    Wilson, M.; Blumhardt, L.D.; Morgan, P.S.

    2002-01-01

    Quantitative diffusion-weighted MRI has been applied to the study of neurological diseases, including multiple sclerosis, where the molecular self-diffusion coefficient D has been measured in both lesions and normal-appearing white matter. Histograms of D have been used as a novel measure of the ''lesion load'', with potential applications that include the monitoring of efficacy in new treatment trials. However different ways of measuring D may affect its value, making comparison between different centres and research groups impossible. We aimed to assess the effect, if any, of using two different MRI sequences on the value of D. We studied 13 healthy volunteers, using two different quantitative diffusion sequences (including different b max values and gradient applications). Maps of D were analysed using both regions of interest (ROI) in white matter and ''whole brain'' histograms, and compared between the two sequences. In addition, we studied three standardised test liquids (with known values of D) using both sequences. Histograms from the two sequences had different distributions, with a greater spread and higher peak position from the sequence with lower b max . This greater spread of D was also evident in the white matter and test liquid ROI. ''Limits of agreement'' analysis demonstrated that the differences could be clinically relevant, despite significant correlations between the sequences obtained using simple rank methods. We conclude that different quantitative diffusion sequences are unlikely to produce directly comparable values of D, particularly if different b max values are used. In addition, the use of inappropriate statistical tests may give false impressions of close agreement. Standardisation of methods for the measurement of D are required if these techniques are to become useful tools, for example in monitoring changes in the disease burden of multiple sclerosis. (orig.)

  4. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

    Science.gov (United States)

    Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

    2016-06-01

    Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, Picotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

    Science.gov (United States)

    Churilla, Thomas M; Ballman, Karla V; Brown, Paul D; Twohy, Erin L; Jaeckle, Kurt; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Garces, Yolanda I; Barker, Fred G; Deming, Richard; Dixon, Jesse G; Burri, Stuart H; Chung, Caroline; Ménard, Cynthia; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2017-12-01

    To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial.

    Science.gov (United States)

    Brown, Paul D; Ballman, Karla V; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Whitton, Anthony C; Greenspoon, Jeffrey; Parney, Ian F; Laack, Nadia N I; Ashman, Jonathan B; Bahary, Jean-Paul; Hadjipanayis, Costas G; Urbanic, James J; Barker, Fred G; Farace, Elana; Khuntia, Deepak; Giannini, Caterina; Buckner, Jan C; Galanis, Evanthia; Roberge, David

    2017-08-01

    Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001

  7. Robust and fast nonlinear optimization of diffusion MRI microstructure models.

    Science.gov (United States)

    Harms, R L; Fritz, F J; Tobisch, A; Goebel, R; Roebroeck, A

    2017-07-15

    Advances in biophysical multi-compartment modeling for diffusion MRI (dMRI) have gained popularity because of greater specificity than DTI in relating the dMRI signal to underlying cellular microstructure. A large range of these diffusion microstructure models have been developed and each of the popular models comes with its own, often different, optimization algorithm, noise model and initialization strategy to estimate its parameter maps. Since data fit, accuracy and precision is hard to verify, this creates additional challenges to comparability and generalization of results from diffusion microstructure models. In addition, non-linear optimization is computationally expensive leading to very long run times, which can be prohibitive in large group or population studies. In this technical note we investigate the performance of several optimization algorithms and initialization strategies over a few of the most popular diffusion microstructure models, including NODDI and CHARMED. We evaluate whether a single well performing optimization approach exists that could be applied to many models and would equate both run time and fit aspects. All models, algorithms and strategies were implemented on the Graphics Processing Unit (GPU) to remove run time constraints, with which we achieve whole brain dataset fits in seconds to minutes. We then evaluated fit, accuracy, precision and run time for different models of differing complexity against three common optimization algorithms and three parameter initialization strategies. Variability of the achieved quality of fit in actual data was evaluated on ten subjects of each of two population studies with a different acquisition protocol. We find that optimization algorithms and multi-step optimization approaches have a considerable influence on performance and stability over subjects and over acquisition protocols. The gradient-free Powell conjugate-direction algorithm was found to outperform other common algorithms in terms of

  8. Development of new auxiliary basis functions of the Karlsruhe segmented contracted basis sets including diffuse basis functions (def2-SVPD, def2-TZVPPD, and def2-QVPPD) for RI-MP2 and RI-CC calculations.

    Science.gov (United States)

    Hellweg, Arnim; Rappoport, Dmitrij

    2015-01-14

    We report optimized auxiliary basis sets for use with the Karlsruhe segmented contracted basis sets including moderately diffuse basis functions (Rappoport and Furche, J. Chem. Phys., 2010, 133, 134105) in resolution-of-the-identity (RI) post-self-consistent field (post-SCF) computations for the elements H-Rn (except lanthanides). The errors of the RI approximation using optimized auxiliary basis sets are analyzed on a comprehensive test set of molecules containing the most common oxidation states of each element and do not exceed those of the corresponding unaugmented basis sets. During these studies an unsatisfying performance of the def2-SVP and def2-QZVPP auxiliary basis sets for Barium was found and improved sets are provided. We establish the versatility of the def2-SVPD, def2-TZVPPD, and def2-QZVPPD basis sets for RI-MP2 and RI-CC (coupled-cluster) energy and property calculations. The influence of diffuse basis functions on correlation energy, basis set superposition error, atomic electron affinity, dipole moments, and computational timings is evaluated at different levels of theory using benchmark sets and showcase examples.

  9. White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study

    Science.gov (United States)

    Vogel, Katja; Timmers, Inge; Kumar, Vinod; Nickl-Jockschat, Thomas; Bastiani, Matteo; Roebroek, Alard; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Goebel, Rainer; Seitz, Jochen

    2016-01-01

    Background Anorexia nervosa (AN) often begins in adolescence, however, the understanding of the underlying pathophysiology at this developmentally important age is scarce, impeding early interventions. We used diffusion tensor imaging (DTI) to investigate microstructural white matter (WM) brain changes including an experimental longitudinal follow-up. Methods We acquired whole brain diffusion-weighted brain scans of 22 adolescent female hospitalized patients with AN at admission and nine patients longitudinally at discharge after weight rehabilitation. Patients (10–18 years) were compared to 21 typically developing controls (TD). Tract-based spatial statistics (TBSS) were applied to compare fractional anisotropy (FA) across groups and time points. Associations between average FA values of the global WM skeleton and weight as well as illness duration parameters were analyzed by multiple linear regression. Results We observed increased FA in bilateral frontal, parietal and temporal areas in AN patients at admission compared to TD. Higher FA of the global WM skeleton at admission was associated with faster weight loss prior to admission. Exploratory longitudinal analysis showed this FA increase to be partially normalized after weight rehabilitation. Conclusions Our findings reveal a markedly different pattern of WM microstructural changes in adolescent AN compared to most previous results in adult AN. This could signify a different susceptibility and reaction to semi-starvation in the still developing brain of adolescents or a time-dependent pathomechanism differing with extend of chronicity. Higher FA at admission in adolescents with AN could point to WM fibers being packed together more closely. PMID:27182488

  10. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

    Science.gov (United States)

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl; Sydes, Benjamin; Stephens, Richard; Parmar, Mahesh K; Langley, Ruth E

    2016-10-22

    Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to

  11. Altered brain structural connectivity in post-traumatic stress disorder: a diffusion tensor imaging tractography study.

    Science.gov (United States)

    Long, Zhiliang; Duan, Xujun; Xie, Bing; Du, Handan; Li, Rong; Xu, Qiang; Wei, Luqing; Zhang, Shao-xiang; Wu, Yi; Gao, Qing; Chen, Huafu

    2013-09-25

    Post-traumatic stress disorder (PTSD) is characterized by dysfunction of several discrete brain regions such as medial prefrontal gyrus with hypoactivation and amygdala with hyperactivation. However, alterations of large-scale whole brain topological organization of structural networks remain unclear. Seventeen patients with PTSD in motor vehicle accident survivors and 15 normal controls were enrolled in our study. Large-scale structural connectivity network (SCN) was constructed using diffusion tensor tractography, followed by thresholding the mean factional anisotropy matrix of 90 brain regions. Graph theory analysis was then employed to investigate their aberrant topological properties. Both patient and control group showed small-world topology in their SCNs. However, patients with PTSD exhibited abnormal global properties characterized by significantly decreased characteristic shortest path length and normalized characteristic shortest path length. Furthermore, the patient group showed enhanced nodal centralities predominately in salience network including bilateral anterior cingulate and pallidum, and hippocampus/parahippocamus gyrus, and decreased nodal centralities mainly in medial orbital part of superior frontal gyrus. The main limitation of this study is the small sample of PTSD patients, which may lead to decrease the statistic power. Consequently, this study should be considered an exploratory analysis. These results are consistent with the notion that PTSD can be understood by investigating the dysfunction of large-scale, spatially distributed neural networks, and also provide structural evidences for further exploration of neurocircuitry models in PTSD. © 2013 Elsevier B.V. All rights reserved.

  12. Telomere length and advanced diffusion MRI as biomarkers for repetitive mild traumatic brain injury in adolescent rats

    Directory of Open Access Journals (Sweden)

    David K. Wright

    Full Text Available Mild traumatic brain injuries (mTBI are of worldwide concern in adolescents of both sexes, and repeated mTBI (RmTBI may have serious long-term neurological consequences. As such, the study of RmTBI and discovery of objective biomarkers that can help guide medical decisions is an important undertaking. Diffusion-weighted MRI (DWI, which provides markers of axonal injury, and telomere length (TL are two clinically relevant biomarkers that have been implicated in a number of neurological conditions, and may also be affected by RmTBI. Therefore, this study utilized the lateral impact injury model of RmTBI to investigate changes in diffusion MRI and TL, and how these changes relate to each other. Adolescent male and female rats received either three mTBIs or three sham injuries. The first injury was given on postnatal day 30 (P30, with the repeated injuries separated by four days each. Seven days after the final injury, a sample of ear tissue was collected for TL analysis. Rats were then euthanized and whole brains were collected and fixated for MRI analyses that included diffusion and high-resolution structural sequences. Compared to the sham-injured group, RmTBI rats had significantly shorter TL at seven days post-injury. Analysis of advanced DWI measures found that RmTBI rats had abnormalities in the corpus callosum and cortex at seven days post-injury. Notably, many of the DWI changes were correlated with TL. These findings demonstrate that TL and DWI measurements are changed by RmTBI and may represent clinically applicable biomarkers for this. Keywords: Biomarker, Concussion, Track weighted imaging, Animal model, Diffusion tensor imaging, MRI

  13. Depressive symptoms and neuroanatomical structures in community-dwelling women: A combined voxel-based morphometry and diffusion tensor imaging study with tract-based spatial statistics

    Directory of Open Access Journals (Sweden)

    Yayoi K. Hayakawa

    2014-01-01

    Full Text Available Depressive symptoms, even at a subclinical level, have been associated with structural brain abnormalities. However, previous studies have used regions of interest or small sample sizes, limiting the ability to generalize the results. In this study, we examined neuroanatomical structures of both gray matter and white matter associated with depressive symptoms across the whole brain in a large sample. A total of 810 community-dwelling adult participants underwent measurement of depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D. The participants were not demented and had no neurological or psychiatric history. To examine the gray and white matter volume, we used structural MRI scans and voxel-based morphometry (VBM; to examine the white matter integrity, we used diffusion tensor imaging with tract-based spatial statistics (TBSS. In female participants, VBM revealed a negative correlation between bilateral anterior cingulate gray matter volume and the CES-D score. TBSS showed a CES-D-related decrease in fractional anisotropy and increase in radial and mean diffusivity in several white matter regions, including the right anterior cingulum. In male participants, there was no significant correlation between gray or white matter volume or white matter integrity and the CES-D score. Our results indicate that the reduction in gray matter volume and differences in white matter integrity in specific brain regions, including the anterior cingulate, are associated with depressive symptoms in women.

  14. Depressive symptoms and neuroanatomical structures in community-dwelling women: A combined voxel-based morphometry and diffusion tensor imaging study with tract-based spatial statistics.

    Science.gov (United States)

    Hayakawa, Yayoi K; Sasaki, Hiroki; Takao, Hidemasa; Hayashi, Naoto; Kunimatsu, Akira; Ohtomo, Kuni; Aoki, Shigeki

    2014-01-01

    Depressive symptoms, even at a subclinical level, have been associated with structural brain abnormalities. However, previous studies have used regions of interest or small sample sizes, limiting the ability to generalize the results. In this study, we examined neuroanatomical structures of both gray matter and white matter associated with depressive symptoms across the whole brain in a large sample. A total of 810 community-dwelling adult participants underwent measurement of depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). The participants were not demented and had no neurological or psychiatric history. To examine the gray and white matter volume, we used structural MRI scans and voxel-based morphometry (VBM); to examine the white matter integrity, we used diffusion tensor imaging with tract-based spatial statistics (TBSS). In female participants, VBM revealed a negative correlation between bilateral anterior cingulate gray matter volume and the CES-D score. TBSS showed a CES-D-related decrease in fractional anisotropy and increase in radial and mean diffusivity in several white matter regions, including the right anterior cingulum. In male participants, there was no significant correlation between gray or white matter volume or white matter integrity and the CES-D score. Our results indicate that the reduction in gray matter volume and differences in white matter integrity in specific brain regions, including the anterior cingulate, are associated with depressive symptoms in women.

  15. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

    International Nuclear Information System (INIS)

    Roos, Daniel E.; Wirth, Andrew; Burmeister, Bryan H.; Spry, Nigel A.; Drummond, Katharine J.; Beresford, Jennifer A.; McClure, Beverley E.

    2006-01-01

    We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting

  16. An 8/15-channel Tx/Rx head neck RF coil combination with region-specific B1 + shimming for whole-brain