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  1. Magnetic resonance brain tissue segmentation based on sparse representations

    Science.gov (United States)

    Rueda, Andrea

    2015-12-01

    Segmentation or delineation of specific organs and structures in medical images is an important task in the clinical diagnosis and treatment, since it allows to characterize pathologies through imaging measures (biomarkers). In brain imaging, segmentation of main tissues or specific structures is challenging, due to the anatomic variability and complexity, and the presence of image artifacts (noise, intensity inhomogeneities, partial volume effect). In this paper, an automatic segmentation strategy is proposed, based on sparse representations and coupled dictionaries. Image intensity patterns are singly related to tissue labels at the level of small patches, gathering this information in coupled intensity/segmentation dictionaries. This dictionaries are used within a sparse representation framework to find the projection of a new intensity image onto the intensity dictionary, and the same projection can be used with the segmentation dictionary to estimate the corresponding segmentation. Preliminary results obtained with two publicly available datasets suggest that the proposal is capable of estimating adequate segmentations for gray matter (GM) and white matter (WM) tissues, with an average overlapping of 0:79 for GM and 0:71 for WM (with respect to original segmentations).

  2. Adaptive online learning based tissue segmentation of MR brain images

    NARCIS (Netherlands)

    Damkat, C.

    2007-01-01

    The aging population in the European Union and the US has increased the importance of research in neurodegenerative diseases. Imaging plays an essential role in this endeavor by providing insight to the intricate cellular and inter-cellular processes in living tissues that will otherwise be difficul

  3. Spectromicroscopy of Brain Tissue

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    Frazer, Bradley; Cannara, Rachel; Gilbert, Benjamin; Destasio, Gelsomina; Ogg, Mandy; Gough, Kathy

    2001-03-01

    X-ray PhotoElectron Emission Microscopy (X-PEEM) was originally developed for studying the surface microchemistry of materials science specimens. It has then evolved into a valuable tool to investigate the magnetic properties of materials and the microchemistry of cells and tissues. We used the MEPHISTO X-PEEM instrument, installed at the UW-Synchrotron Radiation Center to detect trace concentrations of non-physiological elements in senile brain tissue specimens. These tissues contain a large number of plaques, in which all the compounds and elements that the brain does not need are disposed and stored. We hypothesized that plaques should contain elements, such as Si, B, and Al which are very abundant on the Earth crust but absent from healthy tissues. We verified this hypothesis with MEPHISTO and found evidence of Si and B, and suspect Al. We also found a higher than normal concentration of Fe.

  4. Brain tissue oxygen-based therapy and outcome after severe traumatic brain injury: a systematic literature review.

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    Nangunoori, Raj; Maloney-Wilensky, Eileen; Stiefel, Michael; Park, Soojin; Andrew Kofke, W; Levine, Joshua M; Yang, Wei; Le Roux, Peter D

    2012-08-01

    Observational clinical studies demonstrate that brain hypoxia is associated with poor outcome after severe traumatic brain injury (TBI). In this study, available medical literature was reviewed to examine whether brain tissue oxygen (PbtO2)-based therapy is associated with improved patient outcome after severe TBI. Clinical studies published between 1993 and 2010 that compared PbtO2-based therapy combined with intracranial and cerebral perfusion pressure (ICP/CPP)-based therapy to ICP/CPP-based therapy alone were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. For analysis, each selected paper had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs) of outcome described by the Glasgow outcome score (GOS). Seven studies that compared ICP/CPP and PbtO2- to ICP/CPP-based therapy were identified. There were no randomized studies and no comparison studies in children. Four studies, published in 2003, 2009, and 2010 that included 491 evaluable patients were used in the final analysis. Among patients who received PbtO2-based therapy, 121(38.8%) had unfavorable and 191 (61.2%) had a favorable outcome. Among the patients who received ICP/CPP-based therapy 104 (58.1%) had unfavorable and 75 (41.9%) had a favorable outcome. Overall PbtO2-based therapy was associated with favorable outcome (OR 2.1; 95% CI 1.4-3.1). Summary results suggest that combined ICP/CPP- and PbtO2-based therapy is associated with better outcome after severe TBI than ICP/CPP-based therapy alone. Cross-organizational practice variances cannot be controlled for in this type of review and so we cannot answer whether PbtO2-based therapy improves outcome. However, the potentially large incremental value of PbtO2-based therapy provides justification for a randomized clinical trial.

  5. Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

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    DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.

    2016-03-01

    Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.

  6. BRAIN FUNCTIONAL IMAGING BASED ON BRAIN TISSUE OXYGEN CONTENT VIA MAGNETIC RESONANCE

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    M.A OGHABIAN

    2003-03-01

    Full Text Available Introduction: FMRI is a new approach in MRI to provide functional data of human brain activities. Some methods such as BOLD contrast, perfusion imaging, diffusion imaging, and spectroscopy in MRI have used to yield functional images. Material and Methods: This research was performed in imaging center of IMAM KHOMEINI hospital in TEHRAN in 1997. The experiments were performed on a conventional 1.5- T picker MR instrument, using a standard head coil. CE – FAST gradient echo images were obtained (TR=100, TE = 35, 128*256 matrix, 10 mm slice, FOV = 250 mm, F.A =25 Degree, NEX = 1, 13 s per image. Images were obtained during sensory - motor stimulation by pressing fingers to each other, coronal oblique images were acquired through central sulcus (precentral gyrus where the related sensory cortex is. Then, the Images were transferred to personal computers in order to eliminate noise and highlight the functional differences. These images were processed by various mathematical methods such as subtraction and student T- test. Results: Although some changes were seen in functional area, there were not significant results by the conventional system protocols. Some new protocols were designed and implemented to increase the sensitivity of the system to functional changes. Discussion: However, more research needs to be done in the future to obtain faster and more efficient techniques and in regard to clinical applications of the method.

  7. Consent for Brain Tissue Donation after Intracerebral Haemorrhage: A Community-Based Study.

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    Neshika Samarasekera

    Full Text Available Spontaneous intracerebral haemorrhage is a devastating form of stroke and its incidence increases with age. Obtaining brain tissue following intracerebral haemorrhage helps to understand its cause. Given declining autopsy rates worldwide, the feasibility of establishing an autopsy-based collection and its generalisability are uncertain.We used multiple overlapping sources of case ascertainment to identify every adult diagnosed with intracerebral haemorrhage between 1st June 2010-31st May 2012, whilst resident in the Lothian region of Scotland. We sought consent from patients with intracerebral haemorrhage (or their nearest relative if the patient lacked mental capacity to conduct a research autopsy.Of 295 adults with acute intracerebral haemorrhage, 110 (37% could not be approached to consider donation. Of 185 adults/relatives approached, 91 (49% consented to research autopsy. There were no differences in baseline demographic variables or markers of intracerebral haemorrhage severity between consenters and non-consenters. Adults who died and became donors (n = 46 differed from the rest of the cohort (n = 249 by being older (median age 80, IQR 76-86 vs. 75, IQR 65-83, p = 0.002 and having larger haemorrhages (median volume 23 ml, IQR 13-50 vs. 13 ml, IQR 4-40; p = 0.002.Nearly half of those approached consent to brain tissue donation after acute intracerebral haemorrhage. The characteristics of adults who gave consent were comparable to those in an entire community, although those who donate early are older and have larger haemorrhage volumes.

  8. Novel Discrete Compactness-Based Training for Vector Quantization Networks: Enhancing Automatic Brain Tissue Classification

    Directory of Open Access Journals (Sweden)

    Ricardo Pérez-Aguila

    2013-01-01

    Full Text Available An approach for nonsupervised segmentation of Computed Tomography (CT brain slices which is based on the use of Vector Quantization Networks (VQNs is described. Images are segmented via a VQN in such way that tissue is characterized according to its geometrical and topological neighborhood. The main contribution rises from the proposal of a similarity metric which is based on the application of Discrete Compactness (DC which is a factor that provides information about the shape of an object. One of its main strengths lies in the sense of its low sensitivity to variations, due to noise or capture defects, in the shape of an object. We will present, compare, and discuss some examples of segmentation networks trained under Kohonen’s original algorithm and also under our similarity metric. Some experiments are established in order to measure the effectiveness and robustness, under our application of interest, of the proposed networks and similarity metric.

  9. An atlas-based fuzzy connectedness method for automatic tissue classification in brain MRI

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yongxin; BAI Jing

    2006-01-01

    A framework incorporating a subject-registered atlas into the fuzzy connectedness (FC) method is proposed for the automatic tissue classification of 3D images of brain MRI. The pre-labeled atlas is first registered onto the subject to provide an initial approximate segmentation. The initial segmentation is used to estimate the intensity histograms of gray matter and white matter. Based on the estimated intensity histograms, multiple seed voxels are assigned to each tissue automatically. The normalized intensity histograms are utilized in the FC method as the intensity probability density function (PDF) directly. Relative fuzzy connectedness technique is adopted in the final classification of gray matter and white matter. Experimental results based on the 20 data sets from IBSR are included, as well as comparisons of the performance of our method with that of other published methods. This method is fully automatic and operator-independent. Therefore, it is expected to find wide applications, such as 3D visualization, radiation therapy planning, and medical database construction.

  10. Impact of Markov Random Field Optimizer on MRI-based Tissue Segmentation in the Aging Brain

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    Schwarz, Christopher G.; Tsui, Alex; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles; Carmichael, Owen

    2013-01-01

    Automatically segmenting brain magnetic resonance images into grey matter, white matter, and cerebrospinal fluid compartments is a fundamentally important neuroimaging problem whose difficulty is heightened in the presence of aging and neurodegenerative disease. Current methods overlap greatly in terms of identifiable algorithmic components, and the impact of specific components on performance is generally unclear in important real-world scenarios involving serial scanning, multiple scanners, and neurodegenerative disease. Therefore we evaluated the impact that one such component, the Markov Random Field (MRF) optimizer that encourages spatially-smooth tissue labelings, has on brain tissue segmentation performance. Two challenging elderly sets were used to test segmentation consistency across scanners and biological plausibility of tissue change estimates; and a simulated young brain data set was used to test accuracy against ground truth. Comparisons among Graph Cuts (GC), Belief Propagation (BP), and Iterative Conditional Modes (ICM) suggested that in the elderly brain, BP and GC provide the highest segmentation performance, with a slight advantage to BP, and that performance is often superior to that provided by popular methods SPM and FAST. Conversely, SPM and FAST excelled in the young brain, thus emphasizing the unique challenges involved in imaging the aging brain. PMID:22256150

  11. Evaluating the microstructure of human brain tissues using synchrotron radiation-based micro-computed tomography

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    Schulz, Georg; Morel, Anne; Imholz, Martha S.; Deyhle, Hans; Weitkamp, Timm; Zanette, Irene; Pfeiffer, Franz; David, Christian; Müller-Gerbl, Magdalena; Müller, Bert

    2010-09-01

    Minimally invasive deep brain neurosurgical interventions require a profound knowledge of the morphology of the human brain. Generic brain atlases are based on histology including multiple preparation steps during the sectioning and staining. In order to correct the distortions induced in the anisotropic, inhomogeneous soft matter and therefore improve the accuracy of brain atlases, a non-destructive 3D imaging technique with the required spatial and density resolution is of great significance. Micro computed tomography provides true micrometer resolution. The application to post mortem human brain, however, is questionable because the differences of the components concerning X-ray absorption are weak. Therefore, magnetic resonance tomography has become the method of choice for three-dimensional imaging of human brain. Because the spatial resolution of this method is limited, an alternative has to be found for the three-dimensional imaging of cellular microstructures within the brain. Therefore, the present study relies on the synchrotron radiationbased micro computed tomography in the recently developed grating-based phase contrast mode. Using data acquired at the beamline ID 19 (ESRF, Grenoble, France) we demonstrate that grating-based tomography yields premium images of human thalamus, which can be used for the correction of histological distortions by 3D non-rigid registration.

  12. Patch-based augmentation of Expectation-Maximization for brain MRI tissue segmentation at arbitrary age after premature birth.

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    Liu, Mengyuan; Kitsch, Averi; Miller, Steven; Chau, Vann; Poskitt, Kenneth; Rousseau, Francois; Shaw, Dennis; Studholme, Colin

    2016-02-15

    Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter.

  13. Photon Entanglement Through Brain Tissue

    Science.gov (United States)

    Shi, Lingyan; Galvez, Enrique J.; Alfano, Robert R.

    2016-12-01

    Photon entanglement, the cornerstone of quantum correlations, provides a level of coherence that is not present in classical correlations. Harnessing it by study of its passage through organic matter may offer new possibilities for medical diagnosis technique. In this work, we study the preservation of photon entanglement in polarization, created by spontaneous parametric down-conversion, after one entangled photon propagates through multiphoton-scattering brain tissue slices with different thickness. The Tangle-Entropy (TS) plots show the strong preservation of entanglement of photons propagating in brain tissue. By spatially filtering the ballistic scattering of an entangled photon, we find that its polarization entanglement is preserved and non-locally correlated with its twin in the TS plots. The degree of entanglement correlates better with structure and water content than with sample thickness.

  14. Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry.

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    Schwartz, Sarah A; Weil, Robert J; Thompson, Reid C; Shyr, Yu; Moore, Jason H; Toms, Steven A; Johnson, Mahlon D; Caprioli, Richard M

    2005-09-01

    Clinical diagnosis and treatment decisions for a subset of primary human brain tumors, gliomas, are based almost exclusively on tissue histology. Approaches for glioma diagnosis can be highly subjective due to the heterogeneity and infiltrative nature of these tumors and depend on the skill of the neuropathologist. There is therefore a critical need to develop more precise, non-subjective, and systematic methods to classify human gliomas. To this end, mass spectrometric analysis has been applied to these tumors to determine glioma-specific protein patterns. Protein profiles have been obtained from human gliomas of various grades through direct analysis of tissue samples using matrix-assisted laser desorption ionization mass spectrometry (MS). Statistical algorithms applied to the MS profiles from tissue sections identified protein patterns that correlated with tumor histology and patient survival. Using a data set of 108 glioma patients, two patient populations, a short-term and a long-term survival group, were identified based on the tissue protein profiles. In addition, a subset of 57 patients diagnosed with high-grade, grade IV, malignant gliomas were analyzed and a novel classification scheme that segregated short-term and long-term survival patients based on the proteomic profiles was developed. The protein patterns described served as an independent indicator of patient survival. These results show that this new molecular approach to monitoring gliomas can provide clinically relevant information on tumor malignancy and is suitable for high-throughput clinical screening.

  15. Computational cell quantification in the human brain tissues based on hard x-ray phase-contrast tomograms

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    Hieber, Simone E.; Bikis, Christos; Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Chicherova, Natalia; Rack, Alexander; Zdora, Marie-Christine; Zanette, Irene; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    Cell visualization and counting plays a crucial role in biological and medical research including the study of neurodegenerative diseases. The neuronal cell loss is typically determined to measure the extent of the disease. Its characterization is challenging because the cell density and size already differs by more than three orders of magnitude in a healthy cerebellum. Cell visualization is commonly performed by histology and fluorescence microscopy. These techniques are limited to resolve complex microstructures in the third dimension. Phase- contrast tomography has been proven to provide sufficient contrast in the three-dimensional imaging of soft tissue down to the cell level and, therefore, offers the basis for the three-dimensional segmentation. Within this context, a human cerebellum sample was embedded in paraffin and measured in local phase-contrast mode at the beamline ID19 (ESRF, Grenoble, France) and the Diamond Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK). After the application of Frangi-based filtering the data showed sufficient contrast to automatically identify the Purkinje cells and to quantify their density to 177 cells per mm3 within the volume of interest. Moreover, brain layers were segmented in a region of interest based on edge detection. Subsequently performed histological analysis validated the presence of the cells, which required a mapping from the two- dimensional histological slices to the three-dimensional tomogram. The methodology can also be applied to further tissue types and shows potential for the computational tissue analysis in health and disease.

  16. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different...

  17. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    profiling of mammalian neural cells using direct analysis by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). MALDI-MS analysis is rapid, sensitive, robust, and specific for large biomolecules in complex matrices. Here, we describe a newly developed...... and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different....... Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...

  18. Temperature Effects on Brain Tissue in Compression

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.04.005

    2013-01-01

    Extensive research has been carried out for at least 50 years to understand the mechanical properties of brain tissue in order to understand the mechanisms of traumatic brain injury (TBI). The observed large variability in experimental results may be due to the inhomogeneous nature of brain tissue and to the broad range of test conditions. However, test temperature is also considered as one of the factors influencing the properties of brain tissue. In this research, the mechanical properties of porcine brain have been investigated at 22C (room temperature) and at 37C (body temperature) while maintaining a constant preservation temperature of approximately 4-5C. Unconfined compression tests were performed at dynamic strain rates of 30 and 50/s using a custom made test apparatus. There was no significant difference (p = 0.8559 - 0.9290) between the average engineering stresses of the brain tissue at the two different temperature conditions. The results of this study should help to understand the behavior of bra...

  19. Rapid and prodium iodide-compatible optical clearing method for brain tissue based on sugar/sugar-alcohol

    Science.gov (United States)

    Yu, Tingting; Qi, Yisong; Wang, Jianru; Feng, Wei; Xu, Jianyi; Zhu, Jingtan; Yao, Yingtao; Gong, Hui; Luo, Qingming; Zhu, Dan

    2016-08-01

    The developed optical clearing methods show great potential for imaging of large-volume tissues, but these methods present some nonnegligible limitations such as complexity of implementation and long incubation times. In this study, we tried to screen out rapid optical clearing agents by means of molecular dynamical simulation and experimental demonstration. According to the optical clearing potential of sugar and sugar-alcohol, we further evaluated the improvement in the optical clearing efficacy of mouse brain samples, imaging depth, fluorescence preservation, and linear deformation. The results showed that drops of sorbitol, sucrose, and fructose could quickly make the mouse brain sample transparent within 1 to 2 min, and induce about threefold enhancement in imaging depth. The former two could evidently enhance the fluorescence intensity of green fluorescent protein (GFP) and prodium iodide (PI) nuclear dye. Fructose could significantly increase the fluorescence intensity of PI, but slightly decrease the fluorescence intensity of GFP. Even though the three agents caused some shrinkage in samples, the contraction in horizontal and longitudinal directions are almost the same.

  20. Histogram-based characterization of healthy and ischemic brain tissues using multiparametric MR imaging including apparent diffusion coefficient maps and relaxometry.

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    Bernarding, J; Braun, J; Hohmann, J; Mansmann, U; Hoehn-Berlage, M; Stapf, C; Wolf, K J; Tolxdorff, T

    2000-01-01

    Decreased, renormalized, or increased values of the calculated apparent diffusion coefficient (ADC) are observed in stroke models. A quantitative description of corresponding tissue states using ADC values may be extended to include true relaxation times. A histogram-based segmentation is well suited for characterizing tissues according to specific parameter combinations irrespective of the heterogeneity found for human healthy and ischemic brain tissues. In a new approach, navigated diffusion-weighted images and ADC maps were incorporated into voxel-based parameter sets of relaxation times (T1, T2), and T1- or T2-weighted images, followed by a supervised histogram-based analysis. Healthy tissues were segmented by incorporating T1 relaxation into the data set, ischemic regions by combining T2- or diffusion-weighted images with ADC maps. Mean values of healthy and pathologic tissues were determined, spatial distributions of the parameter vectors were visualized using color-encoded overlays. One to six days after stroke, ischemic regions exhibited reduced relative mean ADC values.

  1. Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

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    Carlos A Sánchez-Catasús

    Full Text Available Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV and grey matter volumes (GMV and/or perfusion on one side, and the number of optic neuritis (ON attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

  2. Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

    Science.gov (United States)

    Sánchez-Catasús, Carlos A; Cabrera-Gomez, José; Almaguer Melián, William; Giroud Benítez, José Luis; Rodríguez Rojas, Rafael; Bayard, Jorge Bosch; Galán, Lídice; Sánchez, Reinaldo Galvizu; Fuentes, Nancy Pavón; Valdes-Sosa, Pedro

    2013-01-01

    Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

  3. MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

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    Yu, H [Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Lee, Y [Sunnybrook Odette Cancer Centre, Toronto, Ontario (Canada); Ruschin, M [Odette Cancer Centre, Toronto, ON (Canada); Karam, I [Sunnybrook Odette Cancer Center, Toronto, Ontario (Canada); Sahgal, A [University of Toronto, Toronto, ON (Canada)

    2015-06-15

    Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution. Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of

  4. A comparative study of carbon fiber-based microelectrodes for the measurement of nitric oxide in brain tissue.

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    Santos, Ricardo M; Lourenço, Cátia F; Piedade, Ana P; Andrews, Rodney; Pomerleau, François; Huettl, Peter; Gerhardt, Greg A; Laranjinha, João; Barbosa, Rui M

    2008-12-01

    The measurement of Nitric oxide (NO) in real-time has been a major concern due to the involvement of this ubiquitous free radical modulator in several physiological and pathological pathways in tissues. Here we performed a study aiming at evaluating different types of carbon fibers, namely Textron, Amoco, Courtaulds and carbon nanotubes (University of Kentucky) covered with Nafion/o-phenylenediamine (o-PD) for NO measurement in terms of sensitivity, LOD, response time and selectivity against major potential interferents in the brain (ascorbate, nitrite and dopamine). The results indicate that, as compared with the other carbon fibers and nanotubes, Textron carbon fiber microelectrodes coated with two layers of Nafion and o-PD exhibited better characteristics for NO measurement as they are highly selective against ascorbate (>30,000:1), nitrite (>2000:1) and dopamine (>80:1). These coated Textron microelectrodes showed an average sensitivity of 341+/-120pA/microM and a detection limit of 16+/-11nM. The better performance of the Textron fibers is likely related to a stronger adhesion or more uniform coating of the Nafion and o-PD polymers to the fiber surface. In addition, the background current of the Textron carbon fibers is low, contributing to the excellent signal-to-noise for detection of NO.

  5. Organotypic slice culture of embryonic brain tissue.

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    Daza, Ray A M; Englund, Chris; Hevner, Robert F

    2007-12-01

    INTRODUCTIONThis protocol describes how to dissect, assemble, and cultivate mouse embryonic (E) brain tissue from age E11.5 to E18.5 (days) for organotypic slice culture. These preparations can be used for a variety of assays and studies including coculture of different brain regions, cell migration assays, axon guidance assays, and DNA electroporation experiments. During electroporation, an electric current is applied to the surface of a specific target area of the brain slice in order to open holes in the plasma membrane and introduce a plasmid of coding DNA. The floating slice-on-membrane construct helps to preserve the structural integrity of the brain slices, while maintaining easy experimental access and optimal viability. Experiments can be monitored in living slices (e.g., with confocal imaging), and further studies can be completed using slices that have been fixed and cryosectioned at the end of the experiment. Any region of embryonic brain or spinal tissue can be used in this protocol.

  6. Segmentation of Brain Tissues from Magnetic Resonance Images Using Adaptively Regularized Kernel-Based Fuzzy C-Means Clustering.

    Science.gov (United States)

    Elazab, Ahmed; Wang, Changmiao; Jia, Fucang; Wu, Jianhuang; Li, Guanglin; Hu, Qingmao

    2015-01-01

    An adaptively regularized kernel-based fuzzy C-means clustering framework is proposed for segmentation of brain magnetic resonance images. The framework can be in the form of three algorithms for the local average grayscale being replaced by the grayscale of the average filter, median filter, and devised weighted images, respectively. The algorithms employ the heterogeneity of grayscales in the neighborhood and exploit this measure for local contextual information and replace the standard Euclidean distance with Gaussian radial basis kernel functions. The main advantages are adaptiveness to local context, enhanced robustness to preserve image details, independence of clustering parameters, and decreased computational costs. The algorithms have been validated against both synthetic and clinical magnetic resonance images with different types and levels of noises and compared with 6 recent soft clustering algorithms. Experimental results show that the proposed algorithms are superior in preserving image details and segmentation accuracy while maintaining a low computational complexity.

  7. Segmentation of Brain Tissues from Magnetic Resonance Images Using Adaptively Regularized Kernel-Based Fuzzy C-Means Clustering

    Directory of Open Access Journals (Sweden)

    Ahmed Elazab

    2015-01-01

    Full Text Available An adaptively regularized kernel-based fuzzy C-means clustering framework is proposed for segmentation of brain magnetic resonance images. The framework can be in the form of three algorithms for the local average grayscale being replaced by the grayscale of the average filter, median filter, and devised weighted images, respectively. The algorithms employ the heterogeneity of grayscales in the neighborhood and exploit this measure for local contextual information and replace the standard Euclidean distance with Gaussian radial basis kernel functions. The main advantages are adaptiveness to local context, enhanced robustness to preserve image details, independence of clustering parameters, and decreased computational costs. The algorithms have been validated against both synthetic and clinical magnetic resonance images with different types and levels of noises and compared with 6 recent soft clustering algorithms. Experimental results show that the proposed algorithms are superior in preserving image details and segmentation accuracy while maintaining a low computational complexity.

  8. Effect of vitro preservation on mechanical properties of brain tissue

    Science.gov (United States)

    Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

    2017-05-01

    To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

  9. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...... models then use the directions of greatest diffusion as estimates of white matter fibre orientation. Several fibre tracking algorithms have emerged in the last few years that provide reproducible visualizations of three-dimensional fibre bundles. One class of these algorithms is probabilistic...... be used. Within a two year period, no statistical inter- or intra-brain difference in the diffusion coefficient was found in perfusion fixated minipig brains. However, a decreasing tendency in the diffusion coefficient was found at the last time points about 24 months post mortem and might be explained...

  10. Induced hyperthermia in brain tissue in vivo.

    Science.gov (United States)

    Terzis, A J; Nowak, G; Mueller, E; Rentzsch, O; Arnold, H

    1994-01-01

    Concerning hypothermia treatment, knowledge of time-temperature and of temperature distributions within tumor volumes is essential in order to obtain the maximal therapeutic effect. New techniques are being developed to overcome these difficulties. Two different heat sources, a contact Nd:YAG laser system and an automatically controlled high-frequency current system were investigated on 15 rabbits. Changes of the intracerebral temperature were registered at 4 different distances from the energy source. The intracerebral temperature was increased to 42.5 degrees C at a distance of 5 mm to the heat source and maintained at this level for a period of 60 min. The contact Nd:YAG laser system reached 42.5 degrees C at 3 W of output power. Using higher laser output power, brain tissue herniation (brain edema) through the burrhole was observed. The automatically controlled high-frequency current system reached 42.5 degrees C at 18.75 W of output current. A very small herniation of brain tissue could be observed using higher output current. Both heat sources presented an exponential decrease of the temperature profile depending on the distance. The tissue heat clearance was compensated for by intermittent laser or high-frequency current application. Both systems proved efficient for inducing hyperthermia as needed for antitumoral therapy.

  11. Tissue tracking: applications for brain MRI classification

    Science.gov (United States)

    Melonakos, John; Gao, Yi; Tannenbaum, Allen

    2007-03-01

    Bayesian classification methods have been extensively used in a variety of image processing applications, including medical image analysis. The basic procedure is to combine data-driven knowledge in the likelihood terms with clinical knowledge in the prior terms to classify an image into a pre-determined number of classes. In many applications, it is difficult to construct meaningful priors and, hence, homogeneous priors are assumed. In this paper, we show how expectation-maximization weights and neighboring posterior probabilities may be combined to make intuitive use of the Bayesian priors. Drawing upon insights from computer vision tracking algorithms, we cast the problem in a tissue tracking framework. We show results of our algorithm on the classification of gray and white matter along with surrounding cerebral spinal fluid in brain MRI scans. We show results of our algorithm on 20 brain MRI datasets along with validation against expert manual segmentations.

  12. Segmenting and validating brain tissue definitions in the presence of varying tissue contrast.

    Science.gov (United States)

    Bansal, Ravi; Hao, Xuejun; Peterson, Bradley S

    2017-01-01

    We propose a method for segmenting brain tissue as either gray matter or white matter in the presence of varying tissue contrast, which can derive from either differential changes in tissue water content or increasing myelin content of white matter. Our method models the spatial distribution of intensities as a Markov Random Field (MRF) and estimates the parameters for the MRF model using a maximum likelihood approach. Although previously described methods have used similar models to segment brain tissue, accurate model of the conditional probabilities of tissue intensities and adaptive estimates of tissue properties to local intensities generates tissue definitions that are accurate and robust to variations in tissue contrast with age and across illnesses. Robustness to variations in tissue contrast is important to understand normal brain development and to identify the brain bases of neurological and psychiatric illnesses. We used simulated brains of varying tissue contrast to compare both visually and quantitatively the performance of our method with the performance of prior methods. We assessed validity of the cortical definitions by associating cortical thickness with various demographic features, clinical measures, and medication use in our three large cohorts of participants who were either healthy or who had Bipolar Disorder (BD), Autism Spectrum Disorder (ASD), or familial risk for Major Depressive Disorder (MDD). We assessed validity of the tissue definitions using synthetic brains and data for three large cohort of individuals with various neuropsychiatric disorders. Visual inspection and quantitative analyses showed that our method accurately and robustly defined the cortical mantle in brain images with varying contrast. Furthermore, associating the thickness with various demographic and clinical measures generated findings that were novel and supported by histological analyses or were supported by previous MRI studies, thereby validating the cortical

  13. In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

    Directory of Open Access Journals (Sweden)

    Nick Van Laeken

    Full Text Available This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT, obtained via the one- and two- tissue compartment model (1-TC, 2-TC and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC. For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722. Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs.

  14. Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid.

    NARCIS (Netherlands)

    Miners, J.S.; Verbeek, M.M.; Olde Rikkert, M.G.M.; Kehoe, P.G.; Love, S.

    2008-01-01

    Neprilysin, a zinc-metalloendopeptidase, has important roles in the physiology and pathology of many diseases such as hypertension, cancer and Alzheimer's disease. We have developed an immunocapture assay to measure the specific enzyme activity of neprilysin in brain tissue homogenates and

  15. NMR imaging of cell phone radiation absorption in brain tissue

    OpenAIRE

    Gultekin, David H.; Moeller, Lothar

    2012-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance...

  16. Brain-adipose tissue cross talk.

    Science.gov (United States)

    Bartness, Timothy J; Kay Song, C; Shi, Haifei; Bowers, Robert R; Foster, Michelle T

    2005-02-01

    While investigating the reversible seasonal obesity of Siberian hamsters, direct sympathetic nervous system (SNS) postganglionic innervation of white adipose tissue (WAT) has been demonstrated using anterograde and retrograde tract tracers. The primary function of this innervation is lipid mobilization. The brain SNS outflow to WAT has been defined using the pseudorabies virus (PRV), a retrograde transneuronal tract tracer. These PRV-labelled SNS outflow neurons are extensively co-localized with melanocortin-4 receptor mRNA, which, combined with functional data, suggests their involvement in lipolysis. The SNS innervation of WAT also regulates fat cell number, as noradrenaline inhibits and WAT denervation stimulates fat cell proliferation in vitro and in vivo respectively. The sensory innervation of WAT has been demonstrated by retrograde tract tracing, electrophysiological recording and labelling of the sensory-associated neuropeptide calcitonin gene-related peptide in WAT. Local injections of the sensory nerve neurotoxin capsaicin into WAT selectively destroy this innervation. Just as surgical removal of WAT pads triggers compensatory increases in lipid accretion by non-excised WAT depots, capsaicin-induced sensory denervation triggers increases in lipid accretion of non-capsaicin-injected WAT depots, suggesting that these nerves convey information about body fat levels to the brain. Finally, parasympathetic nervous system innervation of WAT has been suggested, but the recent finding of no WAT immunoreactivity for the possible parasympathetic marker vesicular acetylcholine transporter (VAChT) argues against this claim. Collectively, these data suggest several roles for efferent and afferent neural innervation of WAT in body fat regulation.

  17. Brain-adipose tissue neural crosstalk.

    Science.gov (United States)

    Bartness, Timothy J; Song, C Kay

    2007-07-24

    The preponderance of basic obesity research focuses on its development as affected by diet and other environmental factors, genetics and their interactions. By contrast, we have been studying the reversal of a naturally-occurring seasonal obesity in Siberian hamsters. In the course of this work, we determined that the sympathetic innervation of white adipose tissue (WAT) is the principal initiator of lipid mobilization not only in these animals, but in all mammals including humans. We present irrefutable evidence for the sympathetic nervous system (SNS) innervation of WAT with respect to neuroanatomy (including its central origins as revealed by transneuronal viral tract tracers), neurochemistry (norepinephrine turnover studies) and function (surgical and chemical denervation). A relatively unappreciated role of WAT SNS innervation also is reviewed--the control of fat cell proliferation as shown by selective chemical denervation that triggers adipocyte proliferation, although the precise mechanism by which this occurs presently is unknown. There is no, however, equally strong evidence for the parasympathetic innervation of this tissue; indeed, the data largely are negative severely questioning its existence and importance. Convincing evidence also is given for the sensory innervation of WAT (as shown by tract tracing and by markers for sensory nerves in WAT), with suggestive data supporting a possible role in conveying information on the degree of adiposity to the brain. Collectively, these data offer an additional or alternative view to the predominate one of the control of body fat stores via circulating factors that serve as efferent and afferent communicators.

  18. Frequency of brain tissue donation for research after suicide.

    Science.gov (United States)

    Longaray, Vanessa K; Padoan, Carolina S; Goi, Pedro D; da Fonseca, Rodrigo C; Vieira, Daniel C; Oliveira, Francine H de; Kapczinski, Flávio; Magalhães, Pedro V

    2017-01-01

    To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.

  19. Immunohistochemical detection of brain tissue in heated meat products.

    Science.gov (United States)

    Tersteeg, M H G; Koolmees, P A; van Knapen, F

    2002-05-01

    Immunohistochemical methods were used to determine whether brain tissue could be detected in test batches of meat products prepared with known levels of this tissue (0, 1, 5, 10, or 20% bovine brain tissue or 5% porcine brain tissue). Four different, commercially-available antibodies were examined: anti-Neurofilament (anti-NF), anti-MyelinBasicProtein (anti-MBP), anti-NeuronSpecificEnolase (anti-NSE) and anti-GlialFibrillaryAcidicProtein (anti-GFAP). Results obtained with the four antibodies differed with the heat treatment applied to the products (pasteurisation or sterilisation). The amount of immunoreaction product in the raw meat product varied with the antibody, even when the sample contained the same amount of brain tissue. The staining pattern also varied with the antibody. Overall, the anti-MBP antibody proved to be most useful in detecting brain tissue in finely comminuted heated meat products.

  20. NMR imaging of cell phone radiation absorption in brain tissue.

    Science.gov (United States)

    Gultekin, David H; Moeller, Lothar

    2013-01-02

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry.

  1. Inhomogeneous Deformation of Brain Tissue During Tension Tests

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael D; 10.1016/j.commatsci.2012.05.030

    2013-01-01

    Mechanical characterization of brain tissue has been investigated extensively by various research groups over the past fifty years. These properties are particularly important for modelling Traumatic Brain Injury (TBI). In this research, we present the design and calibration of a High Rate Tension Device (HRTD) capable of performing tests up to a maximum strain rate of 90/s. We use experimental and numerical methods to investigate the effects of inhomogeneous deformation of porcine brain tissue during tension at different specimen thicknesses (4.0-14.0 mm), by performing tension tests at a strain rate of 30/s. One-term Ogden material parameters (mu = 4395.0 Pa, alpha = -2.8) were derived by performing an inverse finite element analysis to model all experimental data. A similar procedure was adopted to determine Young's modulus (E= 11200 Pa) of the linear elastic regime. Based on this analysis, brain specimens of aspect ratio (diameter/thickness) S < 1.0 are required to minimise the effects of inhomogeneous...

  2. Tissue-specific sparse deconvolution for brain CT perfusion.

    Science.gov (United States)

    Fang, Ruogu; Jiang, Haodi; Huang, Junzhou

    2015-12-01

    Enhancing perfusion maps in low-dose computed tomography perfusion (CTP) for cerebrovascular disease diagnosis is a challenging task, especially for low-contrast tissue categories where infarct core and ischemic penumbra usually occur. Sparse perfusion deconvolution has been recently proposed to effectively improve the image quality and diagnostic accuracy of low-dose perfusion CT by extracting the complementary information from the high-dose perfusion maps to restore the low-dose using a joint spatio-temporal model. However the low-contrast tissue classes where infarct core and ischemic penumbra are likely to occur in cerebral perfusion CT tend to be over-smoothed, leading to loss of essential biomarkers. In this paper, we propose a tissue-specific sparse deconvolution approach to preserve the subtle perfusion information in the low-contrast tissue classes. We first build tissue-specific dictionaries from segmentations of high-dose perfusion maps using online dictionary learning, and then perform deconvolution-based hemodynamic parameters estimation for block-wise tissue segments on the low-dose CTP data. Extensive validation on clinical datasets of patients with cerebrovascular disease demonstrates the superior performance of our proposed method compared to state-of-art, and potentially improve diagnostic accuracy by increasing the differentiation between normal and ischemic tissues in the brain.

  3. Grating-based tomography of human tissues

    Science.gov (United States)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  4. Brain emotional learning based Brain Computer Interface

    Directory of Open Access Journals (Sweden)

    Abdolreza Asadi Ghanbari

    2012-09-01

    Full Text Available A brain computer interface (BCI enables direct communication between a brain and a computer translating brain activity into computer commands using preprocessing, feature extraction and classification operations. Classification is crucial as it has a substantial effect on the BCI speed and bit rate. Recent developments of brain-computer interfaces (BCIs bring forward some challenging problems to the machine learning community, of which classification of time-varying electrophysiological signals is a crucial one. Constructing adaptive classifiers is a promising approach to deal with this problem. In this paper, we introduce adaptive classifiers for classify electroencephalogram (EEG signals. The adaptive classifier is brain emotional learning based adaptive classifier (BELBAC, which is based on emotional learning process. The main purpose of this research is to use a structural model based on the limbic system of mammalian brain, for decision making and control engineering applications. We have adopted a network model developed by Moren and Balkenius, as a computational model that mimics amygdala, orbitofrontal cortex, thalamus, sensory input cortex and generally, those parts of the brain thought responsible for processing emotions. The developed method was compared with other methods used for EEG signals classification (support vector machine (SVM and two different neural network types (MLP, PNN. The result analysis demonstrated an efficiency of the proposed approach.

  5. Study on the Property Change of Rhizoma Coptidis and Its Ginger Juice Processed Products Based on 5-Ht Level and Brain Tissues Morphology of Rats

    Science.gov (United States)

    Zhong, Lingyun; Tong, Hengli; Lv, Mu; Deng, Yufen

    2017-09-01

    According to the theory of traditional Chinese Medicine (TCM), all Chinese materia medica need to be processed using Pao zhi which is a processing technology before being used in clinic. Ginger juice, made from dried or fresh ginger, is one of the main TCM processing accessories and always used to help change some Chinese materia medica’s properties for its warm or hot nature. The purpose of this paper is to discuss the influence of ginger juice on Rhizoma Coptidis (RC) by determining 5–hydroxytryptamine (5-HT) content and observing morphological changes in the harns tissue of rats. Raw Rhizoma Coptidis (RRC), fresh ginger juice processed Rhizoma Coptidis (FGJPRC), dried juice processed Rhizoma Coptidis (DGJPRC), dried ginger juice (DGJ) and fresh ginger juice (FGJ) were prepared using appropriate methods. Immunohistochemical staining was used to observe the distribution of 5-HT and fluorescence spectrophotometry was applied to determine 5-hydroxytryptamine content in the brain tissue of rats. 5 - HT in brain tissue of the rats of RRC group was distributed most densely, with the highest content. Compared to the blank group, RRC and different ginger processed RC groups could lead to increasing content of 5-HT in rat encephalon, and significant differences in RRC. Compared with the RRC, the 5-HT content in rat encephalon in DGJPRC, FGJPRC, FGJ and DGJ groups reduced, and DGJPRC, FGJPRC groups showed significant difference, FGJ and DGJ groups showed extreme significant differences. The research showed that processing with hot, warm accessories would moderate the cold nature of RC. The cold and hot nature of Traditional Chinese Materia Medica could be expressed by the difference of 5-HT contents and morphological changes of rats’ brain tissue. Simultaneously, the research showed the different excipient of ginger juice would have different effects on the processing of RC.

  6. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

    2017-09-01

    Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

  7. Coronaviruses in brain tissue from patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Dessau, R B; Lisby, G; Frederiksen, J L

    2001-01-01

    Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E...... in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study....

  8. Comparative Tissue Stainability of Lawsonia inermis (Henna) and Eosin as Counterstains to Hematoxylin in Brain Tissues.

    Science.gov (United States)

    Alawa, Judith N; Gideon, Gbenga O; Adetiba, Bamidele; Alawa, Clement B

    2015-04-01

    We hyposthesized that henna staining could provide an alternative to eosin when used as a counterstain to hematoxylin for understanding basic neurohistological principles. Therefore, this study was aimed at investigating the suitability of henna as counterstain to hematoxylin for the demonstration of the layer stratification and cellular distribution in the brain tissue. Henna stained nervous tissue by reacting with the basic elements in proteins via its amino groups. It stained the neuropil and connective tissue membranes brown and effectively outlined the perikarya of neurons with no visible nuclei demonstrating that it is an acidic dye. Henna as a counterstain to hematoxylin demonstrated reliability as a new neurohistological stain. It facilitated identification of cortical layer stratification and cellular distribution in brain tissue sections from Wistar rats. This was comparable to standard hematoxylin and eosin staining as morphological and morphometrical analyses of stained cells did not show significant differences in size or number. This study presents a method for staining with henna and demonstrates that although henna and eosin belong to different dye groups (anthraquinone and xanthenes, respectively) based on their chromophores, they share similar staining techniques and thus could be used interchangeably in neurohistology.

  9. Monocyte Trafficking, Engraftment, and Delivery of Nanoparticles and an Exogenous Gene into the Acutely Inflamed Brain Tissue - Evaluations on Monocyte-Based Delivery System for the Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Hsin-I Tong

    Full Text Available The ability of monocytes and monocyte-derived macrophages (MDM to travel towards chemotactic gradient, traverse tissue barriers, and accumulate precisely at diseased sites makes them attractive candidates as drug carriers and therapeutic gene delivery vehicles targeting the brain, where treatments are often hampered by the blockade of the blood brain barrier (BBB. This study was designed to fully establish an optimized cell-based delivery system using monocytes and MDM, by evaluating their homing efficiency, engraftment potential, as well as carriage and delivery ability to transport nano-scaled particles and exogenous genes into the brain, following the non-invasive intravenous (IV cell adoptive transfer in an acute neuroinflammation mouse model induced by intracranial injection of Escherichia coli lipopolysaccharides. We demonstrated that freshly isolated monocytes had superior inflamed-brain homing ability over MDM cultured in the presence of macrophage colony stimulating factor. In addition, brain trafficking of IV infused monocytes was positively correlated with the number of adoptive transferred cells, and could be further enhanced by transient disruption of the BBB with IV administration of Mannitol, Bradykinin or Serotonin right before cell infusion. A small portion of transmigrated cells was detected to differentiate into IBA-1 positive cells with microglia morphology in the brain. Finally, with the use of superparamagnetic iron oxide nanoparticles SHP30, the ability of nanoscale agent-carriage monocytes to enter the inflamed brain region was validated. In addition, lentiviral vector DHIV-101 was used to introduce green fluorescent protein (GFP gene into monocytes, and the exogenous GFP gene was detected in the brain at 48 hours following IV infusion of the transduced monocytes. All together, our study has set up the optimized conditions for the more-in-depth tests and development of monocyte-mediated delivery, and our data supported

  10. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

    2017-06-22

    Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  12. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  13. Evaluation of three-dimensional anisotropic head model for mapping realistic electromagnetic fields of brain tissues

    Directory of Open Access Journals (Sweden)

    Woo Chul Jeong

    2015-08-01

    Full Text Available Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understand the exact responses inside the human body subject to an injected currents. In this study, we provide the numerical simulation results of electromagnetic field mapping of brain tissues using a MR-based conductivity imaging method. First, we implemented a realistic three-dimensional human anisotropic head model using high-resolution anatomical and diffusion tensor MR images. The voltage, current density, and magnetic flux density of brain tissues were imaged by injecting 1 mA of current through pairs of electrodes on the surface of our head model. The current density map of anisotropic brain tissues was calculated from the measured magnetic flux density based on the linear relationship between the water diffusion tensor and the electrical conductivity tensor. Comparing the current density to the previous isotropic model, the anisotropic model clearly showed the differences between the brain tissues. This originates from the enhanced signals by the inherent conductivity contrast as well as the actual tissue condition resulting from the injected currents.

  14. Evaluation of three-dimensional anisotropic head model for mapping realistic electromagnetic fields of brain tissues

    Science.gov (United States)

    Jeong, Woo Chul; Wi, Hun; Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2015-08-01

    Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR)-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understand the exact responses inside the human body subject to an injected currents. In this study, we provide the numerical simulation results of electromagnetic field mapping of brain tissues using a MR-based conductivity imaging method. First, we implemented a realistic three-dimensional human anisotropic head model using high-resolution anatomical and diffusion tensor MR images. The voltage, current density, and magnetic flux density of brain tissues were imaged by injecting 1 mA of current through pairs of electrodes on the surface of our head model. The current density map of anisotropic brain tissues was calculated from the measured magnetic flux density based on the linear relationship between the water diffusion tensor and the electrical conductivity tensor. Comparing the current density to the previous isotropic model, the anisotropic model clearly showed the differences between the brain tissues. This originates from the enhanced signals by the inherent conductivity contrast as well as the actual tissue condition resulting from the injected currents.

  15. Development and organization of the human brain tissue compartments across the lifespan using diffusion tensor imaging.

    Science.gov (United States)

    Hasan, Khader M; Sankar, Ambika; Halphen, Christopher; Kramer, Larry A; Brandt, Michael E; Juranek, Jenifer; Cirino, Paul T; Fletcher, Jack M; Papanicolaou, Andrew C; Ewing-Cobbs, Linda

    2007-10-29

    We used a diffusion tensor imaging-based whole-brain tissue segmentation to characterize age-related changes in (a) whole-brain grey matter, white matter, and cerebrospinal fluid relative to intracranial volume and (b) the corresponding brain tissue microstructure using measures of diffusion tensor anisotropy and mean diffusivity. The sample, a healthy cohort of 119 right-handed males and females aged 7-68 years. Our results demonstrate that white matter and grey matter volumes and their corresponding diffusion tensor anisotropy and mean diffusivity follow nonlinear trajectories with advancing age. In contrast, cerebrospinal fluid volume increases linearly with age.

  16. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  17. In vivo detection of epileptic brain tissue using static fluorescence and diffuse reflectance spectroscopy.

    Science.gov (United States)

    Yadav, Nitin; Bhatia, Sanjiv; Ragheb, John; Mehta, Rupal; Jayakar, Prasanna; Yong, William; Lin, Wei-Chiang

    2013-02-01

    Diffuse reflectance and fluorescence spectroscopy are used to detect histopathological abnormalities of an epileptic brain in a human subject study. Static diffuse reflectance and fluorescence spectra are acquired from normal and epileptic brain areas, defined by electrocorticography (ECoG), from pediatric patients undergoing epilepsy surgery. Biopsy specimens are taken from the investigated sites within an abnormal brain. Spectral analysis reveals significant differences in diffuse reflectance spectra and the ratio of fluorescence and diffuse reflectance spectra from normal and epileptic brain areas defined by ECoG and histology. Using these spectral differences, tissue classification models with accuracy above 80% are developed based on linear discriminant analysis. The differences between the diffuse reflectance spectra from the normal and epileptic brain areas observed in this study are attributed to alterations in the static hemodynamic characteristics of an epileptic brain, suggesting a unique association between the histopathological and the hemodynamic abnormalities in an epileptic brain.

  18. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  19. Investigation of elemental changes in brain tissues following excitotoxic injury

    Science.gov (United States)

    Siegele, Rainer; Howell, Nicholas R.; Callaghan, Paul D.; Pastuovic, Zeljko

    2013-07-01

    Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca+2 cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca+2 cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma.

  20. Investigation of elemental changes in brain tissues following excitotoxic injury

    Energy Technology Data Exchange (ETDEWEB)

    Siegele, Rainer, E-mail: rns@ansto.gov.au [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Howell, Nicholas R.; Callaghan, Paul D. [Life Sciences, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Pastuovic, Zeljko [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

    2013-07-01

    Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca{sup +2} cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca{sup +2} cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma.

  1. Estimation of Drug Binding to Brain Tissue: Methodology and in Vivo Application of a Distribution Assay in Brain Polar Lipids.

    Science.gov (United States)

    Belli, Sara; Assmus, Frauke; Wagner, Bjoern; Honer, Michael; Fischer, Holger; Schuler, Franz; Alvarez-Sánchez, Rubén

    2015-12-01

    The unbound drug concentration-effect relationship in brain is a key aspect in CNS drug discovery and development. In this work, we describe an in vitro high-throughput distribution assay between an aqueous buffer and a microemulsion of porcine brain polar lipids (BPL). The derived distribution coefficient LogDBPL was applied to the prediction of unbound drug concentrations in brain (Cu,b) and nonspecific binding to brain tissue. The in vivo relevance of the new assay was assessed for a large set of proprietary drug candidates and CNS drugs by (1) comparing observed compound concentrations in rat CSF with Cu,b calculated using the LogDBPL assay in combination with total drug brain concentrations, (2) comparing Cu,b derived from LogDBPL and total drug brain concentrations to Cu,b estimated using in vitro P-glycoprotein efflux ratio data and unbound drug plasma levels, and (3) comparing tissue nonspecific binding data from human brain autoradiography studies for 17 PET tracer candidates to distribution in BPL. In summary, the LogDBPL assay provides a predicted drug fraction unbound in brain tissue that is nearly identical to brain homogenate equilibrium dialysis with an estimation of in vivo Cu,b that is superior to LogD in octanol. LogDBPL complements the approach for predicting Cu,b based on in vitro P-glycoprotein efflux ratio and in vivo unbound plasma concentration and stands as a fast and cost-effective tool for nonspecific brain binding optimization of PET ligand candidates.

  2. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

    OpenAIRE

    Sutherland, Greg T.; Sheedy, Donna; Kril, Jillian J.

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic n...

  3. In Search of...Brain-Based Education.

    Science.gov (United States)

    Bruer, John T.

    1999-01-01

    Debunks two ideas appearing in brain-based education articles: the educational significance of brain laterality (right brain versus left brain) and claims for a sensitive period of brain development in young children. Brain-based education literature provides a popular but misleading mix of fact, misinterpretation, and fantasy. (47 references (MLH)

  4. Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    WANG Qiong; LI Ai-lin; ZHI Da-shi; HUANG Hui-ling

    2007-01-01

    Objective:To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.Methods: Thirty-one patients with STBI ( GCS ≤8) were randomly divided into hypothermic group (Group A) and control group (Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.Results: In comparison with the control group, lactate/glucose ratio ( L/G) , lactate/pyruvate ratio ( L/P) and glycerol (Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.Conclusions: Mild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

  5. Progression of thanatophagy in cadaver brain and heart tissues

    Directory of Open Access Journals (Sweden)

    Gulnaz T. Javan

    2016-03-01

    Full Text Available Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully elucidated whether postmortem autophagy, also known as thanatophagy, occurs in dead bodies is a function of the time of death. In this study, we tested the hypothesis that thanatophagy would increase in proportion to time elapsed since death for tissues collected from cadavers. Brain and heart tissue from corpses at different time intervals after death were analyzed by Western blot. Densitometry analysis demonstrated that thanatophagy occurred in a manner that was dependent on the time of death. The autophagy-associated proteins, LC3 II, p62, Beclin-1 and Atg7, increased in a time-dependent manner in heart tissues. A potent inducer of autophagy, BNIP3, decreased in the heart tissues as time of death increased, whereas the protein levels increased in brain tissues. However, there was no expression of BNIP3 at extended postmortem intervals in both brain and heart samples. Collectively, the present study demonstrates for the first time that thanatophagy occurs in brain and heart tissues of cadavers in a time-dependent manner. Further, our data suggest that cerebral thanatophagy may occur in a Beclin-1- independent manner. This unprecedented study provides potential insight into thanatophagy as a novel method for the estimation of the time of death in criminal investigationsAbstract: Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully

  6. A Simplified Workflow for Protein Quantitation of Rat Brain Tissues Using Label-Free Proteomics and Spectral Counting.

    Science.gov (United States)

    Boutté, Angela M; Grant, Shonnette F; Dave, Jitendra R

    2016-01-01

    Mass spectrometry-based proteomics is an increasingly valuable tool for determining relative or quantitative protein abundance in brain tissues. A plethora of technical and analytical methods are available, but straightforward and practical approaches are often needed to facilitate reproducibility. This aspect is particularly important as an increasing number of studies focus on models of traumatic brain injury or brain trauma, for which brain tissue proteomes have not yet been fully described. This text provides suggested techniques for robust identification and quantitation of brain proteins by using molecular weight fractionation prior to mass spectrometry-based proteomics. Detailed sample preparation and generalized protocols for chromatography, mass spectrometry, spectral counting, and normalization are described. The rat cerebral cortex isolated from a model of blast-overpressure was used as an exemplary source of brain tissue. However, these techniques may be adapted for lysates generated from several types of cells or tissues and adapted by the end user.

  7. A High Rate Tension Device for Characterizing Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1177/1754337112436900

    2013-01-01

    The mechanical characterization of brain tissue at high loading velocities is vital for understanding and modeling Traumatic Brain Injury (TBI). The most severe form of TBI is diffuse axonal injury (DAI) which involves damage to individual nerve cells (neurons). DAI in animals and humans occurs at strains > 10% and strain rates > 10/s. The mechanical properties of brain tissues at these strains and strain rates are of particular significance, as they can be used in finite element human head models to accurately predict brain injuries under different impact conditions. Existing conventional tensile testing machines can only achieve maximum loading velocities of 500 mm/min, whereas the Kolsky bar apparatus is more suitable for strain rates > 100/s. In this study, a custom-designed high rate tension device is developed and calibrated to estimate the mechanical properties of brain tissue in tension at strain rates < 90/s, while maintaining a uniform velocity. The range of strain can also be extended to 100% de...

  8. Injury Response of Resected Human Brain Tissue In Vitro.

    Science.gov (United States)

    Verwer, Ronald W H; Sluiter, Arja A; Balesar, Rawien A; Baaijen, Johannes C; de Witt Hamer, Philip C; Speijer, Dave; Li, Yichen; Swaab, Dick F

    2015-07-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy. © 2014 International Society of Neuropathology.

  9. Decreased relative brain tissue levels of inositol in fetal hydrocephalus.

    NARCIS (Netherlands)

    Kok, R.D.; Steegers-Theunissen, R.P.M.; Eskes, T.K.A.B.; Heerschap, A.; Berg, P.P. van den

    2003-01-01

    OBJECTIVE: Inositol seems to play a role in the development of the central nervous system. In this study, the brain tissue level of inositol in fetal hydrocephalus was compared with that of healthy control subjects. STUDY DESIGN: Proton magnetic resonance spectroscopy was used to examine the inosito

  10. A novel three-phase model of brain tissue microstructure.

    Science.gov (United States)

    Gevertz, Jana L; Torquato, Salvatore

    2008-08-15

    We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure.

  11. A novel three-phase model of brain tissue microstructure.

    Directory of Open Access Journals (Sweden)

    Jana L Gevertz

    Full Text Available We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure.

  12. Iron biomineralization of brain tissue and neurodegenerative disorders

    Science.gov (United States)

    Mikhaylova (Mikhailova), Albina

    The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies

  13. EEG abnormalities in clinically diagnosed brain death organ donors in Iranian tissue bank.

    Science.gov (United States)

    Tavakoli, Seyed Amir Hossein; Khodadadi, Abbas; Azimi Saein, Amir Reza; Bahrami-Nasab, Hasan; Hashemi, Behnam; Tirgar, Niloufar; Nozary Heshmati, Behnaz

    2012-01-01

    Brain death is defined as the permanent, irreversible and concurrent loss of all brain and brain stem functions. Brain death diagnosis is based on clinical criteria and it is not routine to use paraclinical studies. In some countries, electroencephalogram (EEG) is performed in all patients for the determination of brain death while there is some skepticism in relying on EEG as a confirmatory test for brain death diagnosis. In this study, we assessed the validity of EEG and its abnormalities in brain death diagnosis. In this retrospective study, we used 153 EEGs from medical records of 89 brain death patients in organ procurement unit of the Iranian Tissue Bank admitted during 2002-2008. We extracted and analyzed information including EEGs, which were examined by a neurologist for waves, artifacts and EEG abnormalities. The mean age of the patients was 27.2±12.7 years. The most common cause of brain death was multiple traumas due to accident (65%). The most prevalent artifact was electrical transformer. 125 EEGs (82%) were isoelectric (ECS) and seven EEGs (5%) were depictive of some cerebral activity which upon repeat EEGs, they showed ECS patterns too. There was no relationship between cause of brain death and cerebral activity in EEGs of the patients. In this study, we could confirm ECS patterns in all brain death patients whose status had earlier been diagnosed clinically. Considering the results of this study, it seems sensible to perform EEG as a final confirmatory test as an assurance to the patients' families.

  14. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    Directory of Open Access Journals (Sweden)

    Richard eBeare

    2016-03-01

    Full Text Available Measuring the distribution of brain tissue types (tissue classification in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation, which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF, hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T2-weighted images of preterm infants (born ≤30 weeks’ gestation acquired at 30 weeks’ corrected gestational age (n= 5, coronal T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5 and axial T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5. The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR group, consisted of T2-weighted images of preterm infants (born <30 weeks’ gestation acquired shortly after birth (n= 12, preterm infants acquired at term-equivalent age (n= 12, and healthy term-born infants (born ≥38 weeks’ gestation acquired within the first nine days of life (n= 12. For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for

  15. Determination of Friction Coefficient in Unconfined Compression of Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.05.001

    2013-01-01

    Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow for homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was adopted to estimate the dynamic friction coefficient mu of porcine brain matter against metal platens in compressive tests. Cylindrical samples of porcine brain tissue were tested up to 30% strain at variable strain rates, both under bonded and lubricated conditions in the same controlled environment. It was established that mu was equal to 0.09 +/- 0.03, 0.18 +/- 0.04, 0.18 +/- 0.04 and 0.20 +/- 0.02 at strain rates of...

  16. Optimal Gaussian Mixture Models of Tissue Intensities in Brain MRI of Patients with Multiple-Sclerosis

    Science.gov (United States)

    Xiao, Yiming; Shah, Mohak; Francis, Simon; Arnold, Douglas L.; Arbel, Tal; Collins, D. Louis

    Brain tissue segmentation is important in studying markers in human brain Magnetic Resonance Images (MRI) of patients with diseases such as Multiple Sclerosis (MS). Parametric segmentation approaches typically assume unimodal Gaussian distributions on MRI intensities of individual tissue classes, even in applications on multi-spectral images. However, this assumption has not been rigorously verified especially in the context of MS. In this work, we evaluate the local MRI intensities of both healthy and diseased brain tissues of 21 multi-spectral MRIs (63 volumes in total) of MS patients for adherence to this assumption. We show that the tissue intensities are not uniform across the brain and vary across (anatomical) regions of the brain. Consequently, we show that Gaussian mixtures can better model the multi-spectral intensities. We utilize an Expectation Maximization (EM) based approach to learn the models along with a symmetric Jeffreys divergence criterion to study differences in intensity distributions. The effects of these findings are also empirically verified on automatic segmentation of brains with MS.

  17. Partial volume effect modeling for segmentation and tissue classification of brain magnetic resonance images: A review.

    Science.gov (United States)

    Tohka, Jussi

    2014-11-28

    Quantitative analysis of magnetic resonance (MR) brain images are facilitated by the development of automated segmentation algorithms. A single image voxel may contain of several types of tissues due to the finite spatial resolution of the imaging device. This phenomenon, termed partial volume effect (PVE), complicates the segmentation process, and, due to the complexity of human brain anatomy, the PVE is an important factor for accurate brain structure quantification. Partial volume estimation refers to a generalized segmentation task where the amount of each tissue type within each voxel is solved. This review aims to provide a systematic, tutorial-like overview and categorization of methods for partial volume estimation in brain MRI. The review concentrates on the statistically based approaches for partial volume estimation and also explains differences to other, similar image segmentation approaches.

  18. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    Directory of Open Access Journals (Sweden)

    D Case

    2016-10-01

    Full Text Available Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on the strains/stresses and pressure gradients and concentrations created in the brain tissue due to propagation of waves produced by the impact through the complex internal structure of the human head. This approach has the potential to expand our understanding of the mechanism of brain injury, and to better assess the risk of delayed neurological disorders for tens of thousands of young athletes throughout the world.

  19. Extraction of optical properties and prediction of light distribution in rat brain tissue

    Science.gov (United States)

    Azimipour, Mehdi; Baumgartner, Ryan; Liu, Yuming; Jacques, Steven L.; Eliceiri, Kevin; Pashaie, Ramin

    2014-07-01

    ) and three different wavelengths (405, 532, and 635 nm) in the visible range of the spectrum. A three-dimensional atlas of the rat brain optical properties was constructed based on the experimental measurements. This database was linked to a Monte Carlo toolbox to simulate light distribution in the tissue for different light source configurations.

  20. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  1. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  2. A hybrid hierarchical approach for brain tissue segmentation by combining brain atlas and least square support vector machine.

    Science.gov (United States)

    Kasiri, Keyvan; Kazemi, Kamran; Dehghani, Mohammad Javad; Helfroush, Mohammad Sadegh

    2013-10-01

    In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth.

  3. Distribution of opiate alkaloids in brain tissue of experimental animals.

    Science.gov (United States)

    Djurendic-Brenesel, Maja; Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-12-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography-mass spectrometry (GC-MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake.

  4. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

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    Guangjun Zhao

    2016-01-01

    Full Text Available Cryosection brain images in Chinese Visible Human (CVH dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel. Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  5. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

    Science.gov (United States)

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  6. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Directory of Open Access Journals (Sweden)

    P.R.B. Diniz

    2010-01-01

    Full Text Available The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

  7. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, P.R.B.; Brum, D.G. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Neurociencias e Ciencias do Comportamento; Santos, A. C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Clinica Medica; Murta-Junior, L.O.; Araujo, D.B. de, E-mail: murta@usp.b [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Fisica e Matematica

    2010-01-15

    The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously. (author)

  8. BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2003-04-01

    Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

  9. Influence of preservation temperature on the measured mechanical properties of brain tissue.

    Science.gov (United States)

    Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

    2013-04-26

    The large variability in experimentally measured mechanical properties of brain tissue is due to many factors including heterogeneity, anisotropy, age dependence and post-mortem time. Moreover, differences in test protocols also influence these measured properties. This paper shows that the temperature at which porcine brain tissue is stored or preserved prior to testing has a significant effect on the mechanical properties of brain tissue, even when tests are conducted at the same temperatures. Three groups of brain tissue were stored separately for at least 1h at three different preservation temperatures, i.e., ice cold, room temperature (22 °C) and body temperature (37 °C), prior to them all being tested at room temperature (~22 °C). Significant differences in the corresponding initial elastic shear modulus μ (Pa) (at various amounts of shear, 0≤K≤1.0) were observed. The initial elastic moduli were 1043±271 Pa, 714±210 Pa and 497±156 Pa (mean±SD) at preservation temperatures of ice cold, 22 °C and 37 °C, respectively. Based on this investigation, it is strongly recommended that brain tissue samples must be preserved at an ice-cold temperature prior to testing in order to minimize the difference between the measured in vitro test results and the in vivo properties. A by-product of the study is that simple shear tests allow for large, almost perfectly homogeneous deformation of brain matter. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Diattenuation of brain tissue and its impact on 3D polarized light imaging

    Science.gov (United States)

    Menzel, Miriam; Reckfort, Julia; Weigand, Daniel; Köse, Hasan; Amunts, Katrin; Axer, Markus

    2017-01-01

    3D-polarized light imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue – diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI. PMID:28717561

  11. DNA extraction from fresh-frozen and formalin-fixed, paraffin-embedded human brain tissue.

    Science.gov (United States)

    Wang, Jian-Hua; Gouda-Vossos, Amany; Dzamko, Nicolas; Halliday, Glenda; Huang, Yue

    2013-10-01

    Both fresh-frozen and formalin-fixed, paraffin-embedded (FFPE) human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases, especially neurodegenerative disorders. To identify the optimal method for DNA extraction from human brain tissue, we compared methods on differently-processed tissues. Fragments of LRRK2 and MAPT (257 bp and 483 bp/245 bp) were amplified for evaluation. We found that for FFPE samples, the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method (successful DNA extraction from 76% versus 33% of samples). PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE samples. In the fresh-frozen samples, the DNA extraction success rate was 100% using either a commercial kit (QIAamp DNA Micro) or a laboratory-based method (sample boiling in 0.1 mol/L NaOH, followed by proteinase K digestion, and then DNA extraction using Chelex-100) regardless of PCR amplicon length or tissue storage time. Although the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples, fresh brain tissue is recommended for DNA extraction in future neuropathological studies.

  12. Multi-spectral brain tissue segmentation using automatically trained k-Nearest-Neighbor classification.

    Science.gov (United States)

    Vrooman, Henri A; Cocosco, Chris A; van der Lijn, Fedde; Stokking, Rik; Ikram, M Arfan; Vernooij, Meike W; Breteler, Monique M B; Niessen, Wiro J

    2007-08-01

    Conventional k-Nearest-Neighbor (kNN) classification, which has been successfully applied to classify brain tissue in MR data, requires training on manually labeled subjects. This manual labeling is a laborious and time-consuming procedure. In this work, a new fully automated brain tissue classification procedure is presented, in which kNN training is automated. This is achieved by non-rigidly registering the MR data with a tissue probability atlas to automatically select training samples, followed by a post-processing step to keep the most reliable samples. The accuracy of the new method was compared to rigid registration-based training and to conventional kNN-based segmentation using training on manually labeled subjects for segmenting gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) in 12 data sets. Furthermore, for all classification methods, the performance was assessed when varying the free parameters. Finally, the robustness of the fully automated procedure was evaluated on 59 subjects. The automated training method using non-rigid registration with a tissue probability atlas was significantly more accurate than rigid registration. For both automated training using non-rigid registration and for the manually trained kNN classifier, the difference with the manual labeling by observers was not significantly larger than inter-observer variability for all tissue types. From the robustness study, it was clear that, given an appropriate brain atlas and optimal parameters, our new fully automated, non-rigid registration-based method gives accurate and robust segmentation results. A similarity index was used for comparison with manually trained kNN. The similarity indices were 0.93, 0.92 and 0.92, for CSF, GM and WM, respectively. It can be concluded that our fully automated method using non-rigid registration may replace manual segmentation, and thus that automated brain tissue segmentation without laborious manual training is feasible.

  13. Elderly depression diagnostic of diabetic patients by brain tissue pulsatility imaging

    Science.gov (United States)

    Hachemi, Mélouka Elkateb; Remeniéras, Jean-pierre; Desmidt, Thomas; Camus, Vincent; Tranquart, François

    2010-01-01

    Pulsatile motion of brain parenchyma results from cardiac and breathing cycles and consists in a rapid displacement in systole, with slow diastolic recovery. Based on the vascular depression concept and recent studies where a correlation was found between cerebral haemodynamics and depression in the elderly, we emitted the hypothesis that tissue brain motion due to perfusion is correlated to elderly depression associated with cardiovascular risk factors. Tissue Pulsatlity Imaging (TPI) is a new ultrasound technique developed firstly at the University of Washington to assess the brain tissue motion. We used TPI technique to measure the brain displacement of two groups of elderly patients with diabetes as a vascular risk factor. The first group is composed of 11 depressed diabetic patients. The second group is composed of 12 diabetic patients without depressive symptoms. Transcranial acquisitions were performed with a 1.8 MHz ultrasound phased array probe through the right temporal bone window. The acquisition of six cardiac cycles was realized on each patient with a frame rate of 23 frames/s. Displacements estimation was performed by off-line analysis. A significant decrease in brain pulsatility was observed in the group of depressed patients compared to the group of non depressed patients. Mean displacement magnitude was about 44±7 μm in the first group and 68±13 μm in the second group.

  14. Susceptibility Contrast in High Field MRI of Human Brain as a Function of Tissue Iron Content

    Science.gov (United States)

    Yao, Bing; Li, Tie-Qiang; van Gelderen, Peter; Shmueli, Karin; de Zwart, Jacco A.; Duyn, Jeff H.

    2009-01-01

    Magnetic susceptibility provides an important contrast mechanism for MRI. Increasingly, susceptibility-based contrast is being exploited to investigate brain tissue microstructure and to detect abnormal levels of brain iron as these have been implicated in a variety of neuro-degenerative diseases. However, it remains unclear to what extent magnetic susceptibility-related contrast at high field relates to actual brain iron concentrations. In this study, we performed susceptibility weighted imaging as a function of field strength on healthy brains in vivo and post-mortem brain tissues at 1.5T, 3T and 7T. Iron histology was performed on the tissue samples for comparison. The calculated susceptibility-related parameters R2* and signal frequency shift in four iron-rich regions (putamen, globus pallidus, caudate, and thalamus) showed an almost linear dependence (r=0.90 for R2*; r=0.83 for phase, p<0.01) on field strength, suggesting that potential ferritin saturation effects are not relevant to susceptibility-weighted contrast for field strengths up to 7T. The R2* dependence on the putative (literature-based) iron concentration was 0.048 Hz/Tesla/ppm. The histological data from brain samples confirmed the linear dependence of R2* on field strength and showed a slope against iron concentration of 0.0099 Hz/Tesla/ppm dry-weight, which is equivalent to 0.05 Hz/Tesla/ppm wet-weight and closely matched the calculated value in vivo. These results confirm the validity of using susceptibility-weighted contrast as an indicator of iron content in iron-rich brain regions. The absence of saturation effects opens the way to exploit the benefits of MRI at high field strengths for the detection of iron distributions with high sensitivity and resolution. PMID:19027861

  15. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  16. Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging

    NARCIS (Netherlands)

    Anbeek, Petronella; Vincken, Koen L.; Groenendaal, Floris; Koeman, Annemieke; Van Osch, Matthias J. P.; Van der Grond, Jeroen

    2008-01-01

    A fully automated method has been developed for segmentation of four different structures in the neonatal brain: white matter (WM), central gray matter (CEGM), cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation algorithm is based on information from T2-weighted (T2-w) and i

  17. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  18. Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Zhang

    2015-01-01

    Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

  19. Exploration of the R code-based mathematical model for PMI estimation using profiling of RNA degradation in rat brain tissue at different temperatures.

    Science.gov (United States)

    Ma, Jianlong; Pan, Hui; Zeng, Yan; Lv, Yehui; Zhang, Heng; Xue, Aimin; Jiang, Jieqing; Ma, Kaijun; Chen, Long

    2015-12-01

    Precise estimation of postmortem interval (PMI) is crucial in some criminal cases. This study aims to find some optimal markers for PMI estimation and build a mathematical model that could be used in various temperature conditions. Different mRNA and microRNA markers in rat brain samples were detected using real-time fluorescent quantitative PCR at 12 time points within 144 h postmortem and at temperatures of 4, 15, 25, and 35 °C. Samples from 36 other rats were used to verify the animal mathematical model. Brain-specific mir-9 and mir-125b are effective endogenous control markers that are not affected by PMI up to 144 h postmortem under these temperatures, whereas the commonly used U6 is not a suitable endogenous control in this study. Among all the candidate markers, ΔCt (β-actin) has the best correlation coefficient with PMI and was used to build a new model using R software which can simultaneously manage both PMI and temperature parameters. This animal mathematical model is verified using samples from 36 other rats and shows increased accuracy for higher temperatures and longer PMI. In this study, β-actin was found to be an optimal marker to estimate PMI and some other markers were found to be suitable to act as endogenous controls. Additionally, we have used R code software to build a model of PMI estimation that could be used in various temperature conditions.

  20. Brain-Based Research & Language Teaching.

    Science.gov (United States)

    Christison, MaryAnn

    2002-01-01

    Introduces brain-based teaching and learning. Reviews basic biological facts about the human brain and discusses seven principles based on recent research that have practical benefits for English-as-a-Foreign-Language teachers. (Author/VWL)

  1. Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

    Science.gov (United States)

    Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

    2017-01-01

    Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

  2. Optical changes of porcine brain tissue after thermal coagulation

    Science.gov (United States)

    Schwarzmaier, Hans-Joachim; Goldbach, Thomas; Yaroslavsky, Ilya V.; Ulrich, Frank; Bettag, Martin; Kahn, Thomas; Kaufmann, Raimund

    1995-05-01

    Porcine brain tissue is a model for human brain structures in laser induced thermo-therapy. However, its optical properties including possible heat-related changes were basically unknown so far. To simulate laser coagulation, 12 specimens (6 grey and 6 white matter) were heated in a saline bath (80°C, 2 hours) and compared to 11 untreated samples (5 grey and 6 white matter). The optical constants were obtained from transmission (total and collimated) and reflection (diffuse) measurements using the inverse Monte-Carlo method. The absorption coefficient ((mu) a) of untreated grey substance decreased from 0.35 +/- 0.06/mm (340 nm) to 0.03 +/- 0.02/mm (800 nm). The scattering coefficient ((mu) s) varied between 20.42 +/- 3.65/mm (340 nm) and 6.85 +/- 2.07/mm (800 nm). The anisotropy factor (g) increased from 0.848 +/- 0.013 (340 nm) to 0.889 +/- 0.009 (800 nm). Coagulation increased (mu) a up to a factor of 2 (340-540 nm; p Coagulation increased (mu) a by a factor up to 2 (340-800 nm; all data p < 0.05) while (mu) s and g remained unchanged. Thermal denaturation changes the absorption and scattering properties of porcine brain significantly.

  3. Brain tissue pressure measurements in perinatal and adult rabbits.

    Science.gov (United States)

    Hornig, G W; Lorenzo, A V; Zavala, L M; Welch, K

    1987-12-01

    Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

  4. Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study.

    Science.gov (United States)

    Sigurdsson, Sigurdur; Aspelund, Thor; Forsberg, Lars; Fredriksson, Jesper; Kjartansson, Olafur; Oskarsdottir, Bryndis; Jonsson, Palmi V; Eiriksdottir, Gudny; Harris, Tamara B; Zijdenbos, Alex; van Buchem, Mark A; Launer, Lenore J; Gudnason, Vilmundur

    2012-02-15

    Imaging studies have reported conflicting findings on how brain structure differs with age and sex. This may be explained by discrepancies and limitations in study population and study design. We report a study on brain tissue volumes in one of the largest cohorts of individuals studied to date of subjects with high mean age (mean ± standard deviation (SD) 76 ± 6 years). These analyses are based on magnetic resonance imaging (MRI) scans acquired at baseline on 4303 non-demented elderly, and 367 who had a second MRI, on average 2.5 ± 0.2 years later. Tissue segmentation was performed with an automatic image analysis pipeline. Total brain parenchymal (TBP) volume decreased with increasing age while there was an increase in white matter hyperintensities (WMH) in both sexes. A reduction in both normal white matter (NWM)- and gray matter (GM) volume contributed to the brain shrinkage. After adjusting for intra-cranial volume, women had larger brain volumes compared to men (3.32%, p < 0.001) for TBP volume in the cross-sectional analysis. The longitudinal analysis showed a significant age-sex interaction in TBP volume with a greater rate of annual change in men (-0.70%, 95%CI: -0.78% to -0.63%) than women (-0.55%, 95%CI: -0.61% to -0.49%). The annual change in the cross-sectional data was approximately 40% less than the annual change in the longitudinal data and did not show significant age-sex interaction. The findings indicate that the cross-sectional data underestimate the rate of change in tissue volumes with age as the longitudinal data show greater rate of change in tissue volumes with age for all tissues.

  5. Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

    Science.gov (United States)

    Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-06-01

    Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

  6. Gene Expression Profiling during Pregnancy in Rat Brain Tissue.

    Science.gov (United States)

    Mann, Phyllis E

    2014-03-04

    The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases "expectant brain" and "maternal brain". Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  7. Size-dependent long-term tissue response to biostable nanowires in the brain.

    Science.gov (United States)

    Gällentoft, Lina; Pettersson, Lina M E; Danielsen, Nils; Schouenborg, Jens; Prinz, Christelle N; Linsmeier, Cecilia Eriksson

    2015-02-01

    Nanostructured neural interfaces, comprising nanotubes or nanowires, have the potential to overcome the present hurdles of achieving stable communication with neuronal networks for long periods of time. This would have a strong impact on brain research. However, little information is available on the brain response to implanted high-aspect-ratio nanoparticles, which share morphological similarities with asbestos fibres. Here, we investigated the glial response and neuronal loss in the rat brain after implantation of biostable and structurally controlled nanowires of different lengths for a period up to one year post-surgery. Our results show that, as for lung and abdominal tissue, the brain is subject to a sustained, local inflammation when biostable and high-aspect-ratio nanoparticles of 5 μm or longer are present in the brain tissue. In addition, a significant loss of neurons was observed adjacent to the 10 μm nanowires after one year. Notably, the inflammatory response was restricted to a narrow zone around the nanowires and did not escalate between 12 weeks and one year. Furthermore, 2 μm nanowires did not cause significant inflammatory response nor significant loss of neurons nearby. The present results provide key information for the design of future neural implants based on nanomaterials.

  8. Measuring the linear and nonlinear elastic properties of brain tissue with shear waves and inverse analysis.

    Science.gov (United States)

    Jiang, Yi; Li, Guoyang; Qian, Lin-Xue; Liang, Si; Destrade, Michel; Cao, Yanping

    2015-10-01

    We use supersonic shear wave imaging (SSI) technique to measure not only the linear but also the nonlinear elastic properties of brain matter. Here, we tested six porcine brains ex vivo and measured the velocities of the plane shear waves induced by acoustic radiation force at different states of pre-deformation when the ultrasonic probe is pushed into the soft tissue. We relied on an inverse method based on the theory governing the propagation of small-amplitude acoustic waves in deformed solids to interpret the experimental data. We found that, depending on the subjects, the resulting initial shear modulus [Formula: see text] varies from 1.8 to 3.2 kPa, the stiffening parameter [Formula: see text] of the hyperelastic Demiray-Fung model from 0.13 to 0.73, and the third- [Formula: see text] and fourth-order [Formula: see text] constants of weakly nonlinear elasticity from [Formula: see text]1.3 to [Formula: see text]20.6 kPa and from 3.1 to 8.7 kPa, respectively. Paired [Formula: see text] test performed on the experimental results of the left and right lobes of the brain shows no significant difference. These values are in line with those reported in the literature on brain tissue, indicating that the SSI method, combined to the inverse analysis, is an efficient and powerful tool for the mechanical characterization of brain tissue, which is of great importance for computer simulation of traumatic brain injury and virtual neurosurgery.

  9. Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

    Directory of Open Access Journals (Sweden)

    John P. Lowry

    2005-11-01

    Full Text Available In this communication we review selected experiments involving the use ofcarbon paste electrodes (CPEs to monitor and measure brain tissue O2 levels in awakefreely-moving animals. Simultaneous measurements of rCBF were performed using the H2clearance technique. Voltammetric techniques used include both differential pulse (O2 andconstant potential amperometry (rCBF. Mild hypoxia and hyperoxia produced rapidchanges (decrease and increase respectively in the in vivo O2 signal. Neuronal activation(tail pinch and stimulated grooming produced similar increases in both O2 and rCBFindicating that CPE O2 currents provide an index of increases in rCBF when such increasesexceed O2 utilization. Saline injection produced a transient increase in the O2 signal whilechloral hydrate produced slower more long-lasting changes that accompanied the behavioralchanges associated with anaesthesia. Acetazolamide increased O2 levels through an increasein rCBF.

  10. Brain insulin controls adipose tissue lipolysis and lipogenesis.

    Science.gov (United States)

    Scherer, Thomas; O'Hare, James; Diggs-Andrews, Kelly; Schweiger, Martina; Cheng, Bob; Lindtner, Claudia; Zielinski, Elizabeth; Vempati, Prashant; Su, Kai; Dighe, Shveta; Milsom, Thomas; Puchowicz, Michelle; Scheja, Ludger; Zechner, Rudolf; Fisher, Simon J; Previs, Stephen F; Buettner, Christoph

    2011-02-02

    White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Navigation with a passive brain based interface

    NARCIS (Netherlands)

    Erp, J.B.F. van; Werkhoven, P.J.; Thurlings, M.E.; Brouwer, A.-M.

    2009-01-01

    In this paper, we describe a Brain Computer Interface (BCI) for navigation. The system is based on detecting brain signals that are elicited by tactile stimulation on the torso indicating the desired direction.

  12. Navigation with a passive brain based interface

    NARCIS (Netherlands)

    Erp, J.B.F. van; Werkhoven, P.J.; Thurlings, M.E.; Brouwer, A.-M.

    2009-01-01

    In this paper, we describe a Brain Computer Interface (BCI) for navigation. The system is based on detecting brain signals that are elicited by tactile stimulation on the torso indicating the desired direction.

  13. Differential gene expression in brain tissues of aggressive and non-aggressive dogs

    Directory of Open Access Journals (Sweden)

    Tverdal Aage

    2010-06-01

    Full Text Available Abstract Background Canine behavioural problems, in particular aggression, are important reasons for euthanasia of otherwise healthy dogs. Aggressive behaviour in dogs also represents an animal welfare problem and a public threat. Elucidating the genetic background of adverse behaviour can provide valuable information to breeding programs and aid the development of drugs aimed at treating undesirable behaviour. With the intentions of identifying gene-specific expression in particular brain parts and comparing brains of aggressive and non-aggressive dogs, we studied amygdala, frontal cortex, hypothalamus and parietal cortex, as these tissues are reported to be involved in emotional reactions, including aggression. Based on quantitative real-time PCR (qRT-PCR in 20 brains, obtained from 11 dogs euthanised because of aggressive behaviour and nine non-aggressive dogs, we studied expression of nine genes identified in an initial screening by subtraction hybridisation. Results This study describes differential expression of the UBE2V2 and ZNF227 genes in brains of aggressive and non-aggressive dogs. It also reports differential expression for eight of the studied genes across four different brain tissues (amygdala, frontal cortex, hypothalamus, and parietal cortex. Sex differences in transcription levels were detected for five of the nine studied genes. Conclusions The study showed significant differences in gene expression between brain compartments for most of the investigated genes. Increased expression of two genes was associated with the aggression phenotype. Although the UBE2V2 and ZNF227 genes have no known function in regulation of aggressive behaviour, this study contributes to preliminary data of differential gene expression in the canine brain and provides new information to be further explored.

  14. Multigrid Nonlocal Gaussian Mixture Model for Segmentation of Brain Tissues in Magnetic Resonance Images.

    Science.gov (United States)

    Chen, Yunjie; Zhan, Tianming; Zhang, Ji; Wang, Hongyuan

    2016-01-01

    We propose a novel segmentation method based on regional and nonlocal information to overcome the impact of image intensity inhomogeneities and noise in human brain magnetic resonance images. With the consideration of the spatial distribution of different tissues in brain images, our method does not need preestimation or precorrection procedures for intensity inhomogeneities and noise. A nonlocal information based Gaussian mixture model (NGMM) is proposed to reduce the effect of noise. To reduce the effect of intensity inhomogeneity, the multigrid nonlocal Gaussian mixture model (MNGMM) is proposed to segment brain MR images in each nonoverlapping multigrid generated by using a new multigrid generation method. Therefore the proposed model can simultaneously overcome the impact of noise and intensity inhomogeneity and automatically classify 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid. To maintain the statistical reliability and spatial continuity of the segmentation, a fusion strategy is adopted to integrate the clustering results from different grid. The experiments on synthetic and clinical brain MR images demonstrate the superior performance of the proposed model comparing with several state-of-the-art algorithms.

  15. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  16. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    Science.gov (United States)

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42–47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility. PMID:28139694

  17. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    Science.gov (United States)

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42-47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility.

  18. IMPROVED HYBRID SEGMENTATION OF BRAIN MRI TISSUE AND TUMOR USING STATISTICAL FEATURES

    Directory of Open Access Journals (Sweden)

    S. Allin Christe

    2010-08-01

    Full Text Available Medical image segmentation is the most essential and crucial process in order to facilitate the characterization and visualization of the structure of interest in medical images. Relevant application in neuroradiology is the segmentation of MRI data sets of the human brain into the structure classes gray matter, white matter and cerebrospinal fluid (CSF and tumor. In this paper, brain image segmentation algorithms such as Fuzzy C means (FCM segmentation and Kohonen means(K means segmentation were implemented. In addition to this, new hybrid segmentation technique, namely, Fuzzy Kohonen means of image segmentation based on statistical feature clustering is proposed and implemented along with standard pixel value clustering method. The clustered segmented tissue images are compared with the Ground truth and its performance metric is also found. It is found that the feature based hybrid segmentation gives improved performance metric and improved classification accuracy rather than pixel based segmentation.

  19. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  20. Real-time changes in brain tissue oxygen during endovascular treatment of cerebral vasospasm

    DEFF Research Database (Denmark)

    Rasmussen, Rune; Bache, Søren; Stavngaard, Trine

    2015-01-01

    minute-by-minute changes in brain tissue oxygen during balloon angioplasty and intraarterial administration of vasodilators in three patients.Our results confirm that endovascular intervention is capable of not only resolving angiographic vasospasm, but also of normalizing values of brain tissue oxygen...

  1. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  2. Experimental research of mechanical behavior of porcine brain tissue under rotational shear stress.

    Science.gov (United States)

    Li, Gang; Zhang, Jianhua; Wang, Kan; Wang, Mingyu; Gao, Changqing; Ma, Chao

    2016-04-01

    The objective of this paper is to investigate mechanical behavior of porcine brain tissue with a series of rotational shear stress control experiments. To this end, several experiments including stress sweep tests, frequency sweep tests and quasi-static creep tests were designed and conducted with a standard rheometer (HAAKE RheoStress6000). The effects of the loading stress rates to mechanical properties of brain tissue were also studied in stress sweep tests. The results of stress sweep tests performed on the same brain showed that brain tissue had an obvious regional inhomogeneity and the mechanical damage occurred at the rotational shear stress of 10-15Pa. The experimental data from three different loading stress rates demonstrated that the mechanical behavior of porcine brain tissue was loading stress rate dependent. With the decrease of loading stress rate, a stiffer mechanical characteristic of brain tissue was observed and the occurrence of mechanical damage can be delayed to a higher stress. From the results of frequency sweep tests we found that brain tissue had almost completely elastic properties at high frequency area. The nonlinear creep response under the rotational shear stress of 1, 3, 5, 7 and 9Pa was shown in results of creep tests. A new nonlinear viscoelastic solid model was proposed for creep tests and matched well with the test data. Considering the regional differences, loading stress rates and test conditions effects, loss tangent tan δ in porcine brain tissue showed a high uniformity of 0.25-0.45.

  3. Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

    Science.gov (United States)

    Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

    2017-09-01

    Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥ 98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

  4. Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

    Science.gov (United States)

    Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

    2017-04-07

    The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in

  5. Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

    Science.gov (United States)

    Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.

    2016-02-01

    Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain

  6. Age-dependent effect of static magnetic field on brain tissue hydration.

    Science.gov (United States)

    Deghoyan, Anush; Nikoghosyan, Anna; Heqimyan, Armenuhi; Ayrapetyan, Sinerik

    2014-01-01

    Age-dependent effect of Static Magnetic Field (SMF) on rats in a condition of active and inactive Na(+)/K(+) pump was studied for comparison of brain tissues hydration state changes and magnetic sensitivity. Influence of 15 min 0, 2 Tesla (T) SMF on brain tissue hydration of three aged groups of male albino rats was studied. Tyrode's physiological solution and 10(-4) M ouabain was used for intraperitoneal injections. For animal immobilization, the liquid nitrogen was used and the definition of tissue water content was performed by tissue drying method. Initial water content in brain tissues of young animals is significantly higher than in those of adult and aged ones. SMF exposure leads to decrease of water content in brain tissues of young animals and increase in brain tissues of adult and aged ones. In case of ouabain-poisoned animals, SMF gives reversal effects on brain tissue's hydration both in young and aged animals, while no significant effect on adults is observed. It is suggested that initial state of tissue hydration could play a crucial role in animal age-dependent magnetic sensitivity and the main reason for this could be age-dependent dysfunction of Na(+)/K(+) pump.

  7. Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence.

    Science.gov (United States)

    Gazdzinski, Stefan; Durazzo, Timothy C; Meyerhoff, Dieter J

    2005-06-01

    Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.

  8. Phospholipase A2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yao Xuan; Chen Xi; Ji Zongzheng

    2007-01-01

    Objective To survey changes and the significance of phospholipase A2(PLA2) on brain tissue of SD rat in acute pancreatitis. Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct, rat model of severe acute pancreatitis (SAP) was made,and it included four groups: the control group, the sham-operation group, the SAP group and the PLA2 inhibitor-treated group of SAP. Serum amylases, PLA2 and PLA2 in brain tissue were measured and the brain tissue changes were observed. Results There were no significant difference in serum amylases, PLA2 and PLA2 in brain tissue between the sham-operation and the control groups; the levels of serum amylases, PLA2 and PLA2 in brain tissue in the SAP group were higher than those in the control. In the SAP group expansion and hemorrhage of meninges, intracephalic arteriolar hyperemia, in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed, significant differences were found between two groups.Compared with the SAP group, the level of serum amylase, PLA2 and PLA2 in brain tissue were reduced significantly in the treatment group of SAP. Pathological damages in the treatment group were significantly reduced when compared with the SAP group. Conclusion PLA2 might play an important role in brain tissue damages in severe acute pancreatitis.

  9. Unified model of brain tissue microstructure dynamically binds diffusion and osmosis with extracellular space geometry

    Science.gov (United States)

    Yousefnezhad, Mohsen; Fotouhi, Morteza; Vejdani, Kaveh; Kamali-Zare, Padideh

    2016-09-01

    We present a universal model of brain tissue microstructure that dynamically links osmosis and diffusion with geometrical parameters of brain extracellular space (ECS). Our model robustly describes and predicts the nonlinear time dependency of tortuosity (λ =√{D /D* } ) changes with very high precision in various media with uniform and nonuniform osmolarity distribution, as demonstrated by previously published experimental data (D = free diffusion coefficient, D* = effective diffusion coefficient). To construct this model, we first developed a multiscale technique for computationally effective modeling of osmolarity in the brain tissue. Osmolarity differences across cell membranes lead to changes in the ECS dynamics. The evolution of the underlying dynamics is then captured by a level set method. Subsequently, using a homogenization technique, we derived a coarse-grained model with parameters that are explicitly related to the geometry of cells and their associated ECS. Our modeling results in very accurate analytical approximation of tortuosity based on time, space, osmolarity differences across cell membranes, and water permeability of cell membranes. Our model provides a unique platform for studying ECS dynamics not only in physiologic conditions such as sleep-wake cycles and aging but also in pathologic conditions such as stroke, seizure, and neoplasia, as well as in predictive pharmacokinetic modeling such as predicting medication biodistribution and efficacy and novel biomolecule development and testing.

  10. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  11. DREADDs suppress seizure-like activity in a mouse model of pharmacoresistant epileptic brain tissue

    DEFF Research Database (Denmark)

    Avaliani, N.; Andersson, M.; Thomsen, Annika Højrup Runegaard

    2016-01-01

    Epilepsy is a neurological disorder with a prevalence of ≈1% of general population. Available antiepileptic drugs (AEDs) have multiple side effects and are ineffective in 30% of patients. Therefore, development of effective treatment strategies is highly needed, requiring drug-screening models...... in mouse OHSCs. As we also found that STIB in mouse OHSCs is resistant to common AED, valproic acid, collectively our findings suggest that DREADD-based strategy may be effective in suppressing epileptiform activity in a pharamcoresitant epileptic brain tissue....

  12. Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

    Science.gov (United States)

    Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

  13. Effects of formalin fixation on tissue optical properties of in-vitro brain samples

    Science.gov (United States)

    Anand, Suresh; Cicchi, Riccardo; Martelli, Fabrizio; Giordano, Flavio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

    2015-03-01

    Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

  14. Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues.

    Science.gov (United States)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Sherwood, Chet C; Hof, Patrick R; Ely, John J; Li, Yan; Steinhauser, Dirk; Willmitzer, Lothar; Giavalisco, Patrick; Khaitovich, Philipp

    2015-02-18

    Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Emin, David, E-mail: emin@unm.edu [Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131 (United States); Akhtari, Massoud [Semple Institutes for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Ellingson, B. M. [Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Mathern, G. W. [Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States)

    2015-08-15

    We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

  16. Identifying markers of pathology in SAXS data of malignant tissues of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Siu, K.K.W. [School of Physics and Materials Engineering, PO Box 27, Monash University, Victoria 3800 (Australia)]. E-mail: Karen.Siu@spme.monash.edu.au; Butler, S.M. [School of Computer Science and Software Engineering, PO Box 75, Monash University, Victoria 3800 (Australia); Beveridge, T. [School of Physics and Materials Engineering, PO Box 27, Monash University, Victoria 3800 (Australia); Gillam, J.E. [School of Physics and Materials Engineering, PO Box 27, Monash University, Victoria 3800 (Australia); Hall, C.J. [Daresbury Laboratory, Warrington, Cheshire WA4 4AD (United Kingdom); Kaye, A.H. [Department of Surgery, University of Melbourne, Parkville 3050 (Australia); Department of Neurosurgery, Royal Melbourne Hospital, Parkville 3050 (Australia); Lewis, R.A. [Monash Centre for Synchrotron Science, PO Box 27, Monash University, Victoria 3800 (Australia); Mannan, K. [Division of Neurosurgery, University of Saskatchewan, Saskatoon S7N 5E5 (Canada); McLoughlin, G. [Division of Neurosurgery, University of Saskatchewan, Saskatoon S7N 5E5 (Canada); Pearson, S. [Physics and Electronics, University of New England, Armidale, New South Wales 2351 (Australia); Round, A.R. [Department of Materials and Medical Sciences, Cranfield University, Wiltshire SN6 8LA (United Kingdom); Schueltke, E. [Division of Neurosurgery, University of Saskatchewan, Saskatoon S7N 5E5 (Canada); Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon S7N 5E5 (Canada); Department of Neurological Science, Walton Medical Centre, University of Liverpool, L97 LJ (United Kingdom); Webb, G.I. [School of Computer Science and Software Engineering, PO Box 75, Monash University, Victoria 3800 (Australia); Wilkinson, S.J. [Department of Materials and Medical Sciences, Cranfield University, Wiltshire SN6 8LA (United Kingdom)

    2005-08-11

    Conventional neuropathological analysis for brain malignancies is heavily reliant on the observation of morphological abnormalities, observed in thin, stained sections of tissue. Small Angle X-ray Scattering (SAXS) data provide an alternative means of distinguishing pathology by examining the ultra-structural (nanometer length scales) characteristics of tissue. To evaluate the diagnostic potential of SAXS for brain tumors, data was collected from normal, malignant and benign tissues of the human brain at station 2.1 of the Daresbury Laboratory Synchrotron Radiation Source and subjected to data mining and multivariate statistical analysis. The results suggest SAXS data may be an effective classifier of malignancy.

  17. In situ monitoring of brain tissue reaction of chronically implanted electrodes with an optical coherence tomography fiber system

    Science.gov (United States)

    Xie, Yijing; Hassler, Christina; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

    2014-03-01

    Neural microelectrodes are well established tools for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. However, long term implanted neural probes often become functionally impaired by tissue encapsulation. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities provide no sufficient resolution for a cellular measurement in deep brain regions. Optical coherence tomography (OCT) is a well developed imaging modality, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. Further more, a fiber based spectral domain OCT was shown to be capable of minimally invasive brain intervention. In the present study, we propose to use a fiber based spectral domain OCT to monitor the the progression of the tissue's immune response and scar encapsulation of microprobes in a rat animal model. We developed an integrated OCT fiber catheter consisting of an implantable ferrule based fiber cannula and a fiber patch cable. The fiber cannula was 18.5 mm long, including a 10.5 mm ceramic ferrule and a 8.0 mm long, 125 μm single mode fiber. A mating sleeve was used to fix and connect the fiber cannula to the OCT fiber cable. Light attenuation between the OCT fiber cable and the fiber cannula through the mating sleeve was measured and minimized. The fiber cannula was implanted in rat brain together with a microelectrode in sight used as a foreign body to induce the brain tissue immune reaction. Preliminary data showed a significant enhancement of the OCT backscattering signal during the brain tissue scarring process, while the OCT signal of the flexible microelectrode was getting weaker consequentially.

  18. Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue.

    Science.gov (United States)

    Mehrabian, Mohadeseh; Brethour, Dylan; Williams, Declan; Wang, Hansen; Arnould, Hélène; Schneider, Benoit; Schmitt-Ulms, Gerold

    2016-01-01

    A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. For the prion protein (PrP), best known for its role in several invariably fatal neurodegenerative diseases, a natural choice, therefore, would be to undertake such studies with brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used. To identify possible causes for this disparity, we set out to systematically investigate the consequence of PrP deficiency on the global proteome in brain tissue and in four distinct cell models. Here we report that PrP deficiency causes robust but surprisingly divergent changes to the global proteomes of cell models but has no discernible impact on the global brain proteome. Amongst >1,500 proteins whose levels were compared in wild-type and PrP-deficient models, members of the MARCKS protein family exhibited pronounced, yet cell model-dependent changes to their steady-state levels. Follow-up experiments revealed that PrP collaborates with members of the MARCKS protein family in its control of NCAM1 polysialylation. We conclude that the physiological function of PrP may be masked in analyses of complex brain samples but its cell-type specific influence on a lipid raft-based NCAM1-related cell biology comes to the fore in investigations of specific cell types.

  19. Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

    Science.gov (United States)

    Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

    2011-10-15

    Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue.

  20. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  1. Closed Loop Brain Model of Neocortical Information Based Exchange

    Directory of Open Access Journals (Sweden)

    James eKozloski

    2016-01-01

    Full Text Available Here we describe an information based exchange' model of brain function that ascribes to neocortex, basal ganglia, and thalamus distinct network functions. The model allows us to analyze whole brain system set point measures, such as the rate and heterogeneity of transitions in striatum and neocortex, in the context of neuromodulation and other perturbations. Our closed-loop model is grounded in neuroanatomical observations, proposing a novel Grand Loop through neocortex, and invokes different forms of plasticity at specific tissue interfaces and their principle cell synapses to achieve these transitions. By implementing a system for maximum information based exchange of action potentials between modeled neocortical areas, we observe changes to these measures in simulation. We hypothesize that similar dynamic set points and modulations exist in the brain's resting state activity, and that different modifications to information based exchange may shift the risk profile of different component tissues, resulting in different neurodegenerative diseases. This model is targeted for further development using IBM's Neural Tissue Simulator, which allows scalable elaboration of networks, tissues, and their neural and synaptic components towards ever greater complexity and biological realism.

  2. X-ray micro-tomography for investigations of brain tissues on cellular level

    Science.gov (United States)

    Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Zanette, Irene; Zdora, Marie-Christine; Bikis, Christos; Hipp, Alexander; Hieber, Simone E.; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    X-ray imaging in absorption contrast mode is well established for hard tissue visualization. However, performance for lower density materials is limited due to a reduced contrast. Our aim is three-dimensional (3D) characterization of micro-morphology of human brain tissues down to (sub-)cellular resolution within a laboratory environment. Using the laboratory-based microtomography (μCT) system nanotom m (GE Sensing and Inspection Technologies GmbH, Wunstorf, Germany) and synchrotron radiation at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK), we have acquired 3D data with a resolution down to 0.45 μm for visualization of a human cerebellum specimen down to cellular level. We have shown that all selected modalities, namely laboratory-based absorption contrast micro-tomography (LBμCT), synchrotron radiation based in-line single distance phase contrast tomography (SDPR) and synchrotron radiation based single-grating interferometry (GI), can reach cellular resolution for tissue samples with a size in the mm-range. The results are discussed qualitatively in comparison to optical microscopy of haematoxylin and eosin (HE) stained sections. As phase contrast yields to a better data quality for soft tissues and in order to overcome restrictions of limited beamline access for phase contrast measurements, we have equipped the μCT system nanotom m with a double-grating phase contrast set-up. Preliminary experimental results of a knee sample consisting of a bony part and a cartilage demonstrate that phase contrast data exhibits better quality compared to absorption contrast. Currently, the set-up is under adjustment. It is expected that cellular resolution would also be achieved. The questions arise (1) what would be the quality gain of laboratory-based phase contrast in comparison to laboratory-based absorption contrast tomography and (2) could laboratory-based phase contrast data provide comparable results to synchrotron radiation based

  3. Use of flow cytometry for high-throughput cell population estimates in fixed brain tissue

    Directory of Open Access Journals (Sweden)

    Nicole A Young

    2012-07-01

    Full Text Available The numbers and types of cells in an area of cortex define its function. Therefore it is essential to characterize the numbers and distributions of total cells in areas of the cortex, as well as to identify numbers of subclasses of neurons and glial cells. To date, the large size of the primate brain and the lack of innovation in cell counting methods have been a roadblock to obtaining high-resolution maps of cell and neuron density across the cortex in humans and non-human primates. Stereological counting methods and the isotropic fractionator are valuable tools for estimating cell numbers, but are better suited to smaller, well-defined brain structures or to cortex as a whole. In the present study, we have extended our flow-cytometry based counting method, the flow fractionator (Collins et al., 2010a, to include high-throughput total cell population estimates in homogenized cortical samples. We demonstrate that our method produces consistent, accurate and repeatable cell estimates quickly. The estimates we report are in excellent agreement with estimates for the same samples obtained using a Neubauer chamber and a fluorescence microscope. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue is more efficient and more precise than manual counting methods. The addition of automated nuclei counting to our flow fractionator method allows for a fully automated, rapid characterization of total cells and neuronal and non-neuronal populations in human and non-human primate brains, providing valuable data to further our understanding of the functional organization of normal, aging and diseased brains.

  4. A new system for cutting brain tissue preserving vessels: water jet cutting.

    Science.gov (United States)

    Terzis, A J; Nowak, G; Rentzsch, O; Arnold, H; Diebold, J; Baretton, G

    1989-01-01

    The water jet cutting system allows transaction and dissection of biological structures with little bleeding. Structures of higher tissue rigidity remain unchanged while softer tissues are mechanically dissected. In brain tissue, all vessels larger than 20 microns are left intact after the passage of the jet stream with a pressure of up to 5 bar, and therefore vessels can be isolated selectively from the surrounding tissue. Oedema is present adjacent to the cut and no increase of temperature occurs.

  5. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  6. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A;

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

  7. Radiation-induced changes of brain tissue after radiosurgery in patients with arteriovenous malformations: dose/volume-response relations

    Energy Technology Data Exchange (ETDEWEB)

    Levegruen, S.; Schlegel, W. [Dept. of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Hof, H.; Debus, J. [Dept. of Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Essig, M. [Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2004-12-01

    Purpose: to evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging. Patients and methods: data from 73 AVM patients who had stereotactic linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three levels with respect to the extent of the image change (small, intermediate, and large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm{sup 3} (Dmean20) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean20 and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape logistic function and characterized by DV{sub 50}, the dose for a 50% incidence, and the slope parameter k. Results: dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV{sub 50} values of fitted dose/volume-response curves for tissue changes of large extent (e.g., V12{sub 50} = 22.0 {+-} 2.6 cm{sup 3} and Dmean20{sub 50} = 17.8 {+-} 2.0 Gy for the combined endpoint

  8. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high...

  9. Distinct Effects of Ionizing Radiation on In vivo Murine Kidney and Brain Normal Tissue Gene Expression

    National Research Council Canada - National Science Library

    Weiling Zhao; Eric Y. Chuang; Mark Mishra; Rania Awwad; Kheem Bisht; Lunching Sun; Phuongmai Nguyen; J. Daniel Pennington; Tony Jau Cheng Wang; C. Matthew Bradbury; Lei Huang; Zhijun Chen; Gil Bar-Sela; Michael E.C. Robbins; David Gius

    2006-01-01

    Purpose: There is a growing awareness that radiation-induced normal tissue injury in late-responding organs, such as the brain, kidney, and lung, involves complex and dynamic responses between multiple cell...

  10. The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Chang-Gyu Hahn

    Full Text Available Recent molecular genetics studies have suggested various trans-synaptic processes for pathophysiologic mechanisms of neuropsychiatric illnesses. Examination of pre- and post-synaptic scaffolds in the brains of patients would greatly aid further investigation, yet such an approach in human postmortem tissue has yet to be tested. We have examined three methods using density gradient based purification of synaptosomes followed by detergent extraction (Method 1 and the pH based differential extraction of synaptic membranes (Methods 2 and 3. All three methods separated fractions from human postmortem brains that were highly enriched in typical PSD proteins, almost to the exclusion of pre-synaptic proteins. We examined these fractions using electron microscopy (EM and verified the integrity of the synaptic membrane and PSD fractions derived from human postmortem brain tissues. We analyzed protein composition of the PSD fractions using two dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS and observed known PSD proteins by mass spectrometry. Immunoprecipitation and immunoblot studies revealed that expected protein-protein interactions and certain posttranscriptional modulations were maintained in PSD fractions. Our results demonstrate that PSD fractions can be isolated from human postmortem brain tissues with a reasonable degree of integrity. This approach may foster novel postmortem brain research paradigms in which the stoichiometry and protein composition of specific microdomains are examined.

  11. Assessment of murine brain tissue shrinkage caused by different histological fixatives using magnetic resonance and computed tomography imaging.

    Science.gov (United States)

    Wehrl, Hans F; Bezrukov, Ilja; Wiehr, Stefan; Lehnhoff, Mareike; Fuchs, Kerstin; Mannheim, Julia G; Quintanilla-Martinez, Leticia; Kohlhofer, Ursula; Kneilling, Manfred; Pichler, Bernd J; Sauter, Alexander W

    2015-05-01

    Especially for neuroscience and the development of new biomarkers, a direct correlation between in vivo imaging and histology is essential. However, this comparison is hampered by deformation and shrinkage of tissue samples caused by fixation, dehydration and paraffin embedding. We used magnetic resonance (MR) imaging and computed tomography (CT) imaging to analyze the degree of shrinkage on murine brains for various fixatives. After in vivo imaging using 7 T MRI, animals were sacrificed and the brains were dissected and immediately placed in different fixatives, respectively: zinc-based fixative, neutral buffered formalin (NBF), paraformaldehyde (PFA), Bouin-Holland fixative and paraformaldehyde-lysine-periodate (PLP). The degree of shrinkage based on mouse brain volumes, radiodensity in Hounsfield units (HU), as well as non-linear deformations were obtained. The highest degree of shrinkage was observed for PLP (68.1%, P brain shrinkage and only small deformations and is therefore recommended for in vivo ex vivo comparison studies.

  12. Cavitation Induced Structural and Neural Damage in Live Brain Tissue Slices: Relevance to TBI

    Science.gov (United States)

    2014-09-29

    the value of this experimental platform to investigate the single bubble cavitation- induced damage in a biological tissue is illustrated with an...Lei Wu, Malisa Sarntinoranont, Huikai Xie1. Refractive index measurement of acute rat brain tissue slices using optical coherence tomography, Optics...b-TBI, i.e. what is “broken”, in the brain during exposure to shock loading is currently unknown. While blast waves are well known to have negative

  13. Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue

    OpenAIRE

    2012-01-01

    Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity 1,2. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain inj...

  14. Isolation and functional assessment of mitochondria from small amounts of mouse brain tissue.

    Science.gov (United States)

    Chinopoulos, Christos; Zhang, Steven F; Thomas, Bobby; Ten, Vadim; Starkov, Anatoly A

    2011-01-01

    Recent discoveries have brought mitochondria functions in focus of the neuroscience research community and greatly stimulated the demand for approaches to study mitochondria dysfunction in neurodegenerative diseases. Many mouse disease models have been generated, but studying mitochondria isolated from individual mouse brain regions is a challenge because of small amount of the available brain tissue. Conventional techniques for isolation and purification of mitochondria from mouse brain subregions, such as ventral midbrain, hippocampus, or striatum, require pooling brain tissue from six to nine animals for a single mitochondrial preparation. Working with pooled tissue significantly decreases the quality of data because of the time required to dissect several brains. It also greatly increases the labor intensity and the cost of experiments as several animals are required per single data point. We describe a method for isolation of brain mitochondria from mouse striata or other 7-12 mg brain samples. The method utilizes a refrigerated table-top microtube centrifuge, and produces research grade quality mitochondria in amounts sufficient for performing multiple enzymatic and functional assays, thereby eliminating the necessity for pooling mouse brain tissue. We also include a method of measuring ADP-ATP exchange rate as a function of mitochondrial membrane potential (ΔΨm) in small amounts of isolated mitochondria, adapted to a plate reader format.

  15. Evaluation of tissue-equivalent materials to be used as human brain tissue substitute in dosimetry for diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, C.C., E-mail: cassio.c.ferreira@gmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Ximenes Filho, R.E.M., E-mail: raimundoximenes@hotmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Vieira, J.W., E-mail: jwvieira@br.inter.ne [Centro Federal de Educacao Tecnologica de Pernambuco (CEFET-PE), Av. Professor Luiz Freire, 500 Curado, CEP 50740-540, Recife (Brazil); Escola Politecnica de Pernambuco, Universidade de Pernambuco (EPP/UPE), Rua Benfica, 455, Madalena, CEP 50720-001, Recife (Brazil); Tomal, A., E-mail: alessandratomal@pg.ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Garcia, C.A.B., E-mail: cgarcia@ufs.b [Departamento de Quimica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Maia, A.F., E-mail: afmaia@ufs.b [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil)

    2010-08-15

    Tissue-equivalent materials to be used as substitutes for human brain tissue in dosimetry for diagnostic radiology have been investigated in terms of calculated total mass attenuation coefficient ({mu}/{rho}), calculated mass energy-absorption coefficient ({mu}{sub en}/{rho}) and absorbed dose. Measured linear attenuation coefficients ({mu}) have been used for benchmarking the calculated total mass attenuation coefficient ({mu}/{rho}). The materials examined were bolus, nylon (registered) , orange articulation wax, red articulation wax, PMMA (polymethylmethacrylate), bees wax, paraffin I, paraffin II, pitch and water. The results show that water is the best substitute for brain among the materials investigated. The average percentage differences between the calculated {mu}/{rho} and {mu}{sub en}/{rho} coefficients for water and those for brain were 1.0% and 2.5%, respectively. Absorbed doses determined by Monte Carlo methods confirm water as being the best brain substitute to be used in dosimetry for diagnostic radiology, showing maximum difference of 0.01%. Additionally this study showed that PMMA, a material often used for the manufacturing of head phantoms for computed tomography, cannot be considered to be a suitable substitute for human brain tissue in dosimetry.

  16. [Scaffold-based Bone Tissue Engineering].

    Science.gov (United States)

    Holzapfel, B M; Rudert, M; Hutmacher, D W

    2017-08-01

    Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue. In this article we provide an overview about our conceptual design and process of the clinical translation of scaffold-based bone tissue engineering applications.

  17. Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity.

    Science.gov (United States)

    Unhavaithaya, Yingdee; Orr-Weaver, Terry L

    2012-01-01

    Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood-brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.

  18. MRI Brain Image Segmentation based on Thresholding

    Directory of Open Access Journals (Sweden)

    G. Evelin Sujji, Y.V.S. Lakshmi, G. Wiselin Jiji

    2013-03-01

    Full Text Available Medical Image processing is one of the mostchallenging topics in research field. The mainobjective of image segmentation is to extract variousfeatures of the image that are used foranalysing,interpretation and understanding of images.Medical Resonance Image plays a major role inMedical diagnostics. Image processing in MRI ofbrain is highlyessential due to accurate detection ofthe type of brain abnormality which can reduce thechance of fatal result. This paper outlines anefficient image segmentation technique that candistinguish the pathological tissues such asedemaandtumourfrom thenormal tissues such as WhiteMatter(WM,GreyMatter(GM, andCerebrospinal Fluid(CSF. Thresholding is simplerand most commonly used techniques in imagesegmentation. This technique can be used to detectthe contour of thetumourin brain.

  19. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  20. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-01-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40–50 nm, which is not compatible with the ferritin protein, the core of which is typically 6–8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain. PMID:27941952

  1. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-12-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

  2. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    Science.gov (United States)

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

  3. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

    Science.gov (United States)

    Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

    2011-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy.

  4. Effects of different concentrations of pollen extract on brain tissues of Oncorhynchus mykiss

    Institute of Scientific and Technical Information of China (English)

    Mehmet Fuat Gulhan; Hasan Akgul; Taner Dastan; Sevgi Durna Dastan; Zeliha Selamoglu Talas

    2014-01-01

    Objective: To determine the antioxidant capacities of pollen extract applied at different concentrations on biochemical parameters in brain tissues of rainbow trouts. Methods:parameters in brain tissues of fish treated at various concentrations of the pollen extract (0.5, 2.5, 5, 10, 20 and 30 mg/L) for 96 h. The malondialdehyde levels, total antioxidant status, total oxidant status, oxidative stress index and amounts of total free sulfhydryl groups were analyzed in fish brain. Results:The effective concentration of pollen was determined with some biochemical treated compared to control group (P Conclusions: To apply the pollen to fish reduces the detrimental effects and modulates oxidative status via activating antioxidant defense systems at brain tissue. As a result, pollen can be added up to 10 mg/L to the medium of rainbow trout to improve health of fish.

  5. Impedance spectroscopy--an outstanding method for label-free and real-time discrimination between brain and tumor tissue in vivo.

    Science.gov (United States)

    Jahnke, Heinz-Georg; Heimann, Axel; Azendorf, Ronny; Mpoukouvalas, Konstantinos; Kempski, Oliver; Robitzki, Andrea A; Charalampaki, Patra

    2013-08-15

    Until today, brain tumors especially glioblastoma are difficult to treat and therefore, results in a poor survival rate of 0-14% over five years. To overcome this problem, the development of novel therapeutics as well as optimization of neurosurgical procedures to remove the tumor tissue are subject of intensive research. The main problem of the tumor excision, as the primary clinical intervention is the diffuse infiltration of the tumor cells in unaltered brain tissue that complicates the complete removal of residual tumor cells. In this context, we are developing novel approaches for the label-free discrimination between tumor tissue and unaltered brain tissue in real-time during the surgical process. Using our impedance spectroscopy-based measurement system in combination with flexible microelectrode arrays we could successfully demonstrate the discrimination between a C6-glioma and unaltered brain tissue in an in vivo rat model. The analysis of the impedance spectra revealed specific impedance spectrum shape characteristics of physiologic neuronal tissue in the frequency range of 10-500 kHz that were significantly different from the tumor tissue. Moreover, we used an adapted equivalent circuit model to get a deeper understanding for the nature of the observed effects. The impedimetric label-free and real-time discrimination of tumor from unaltered brain tissue offers the possibility for the implementation in surgical instruments to support surgeons to decide, which tissue areas should be removed and which should be remained.

  6. Stress response of bovine artery and rat brain tissue due to combined translational shear and fixed unconfined compression

    Science.gov (United States)

    Leahy, Lauren

    During trauma resulting from impacts and blast waves, sinusoidal waves permeate the brain and cranial arterial tissue, both non-homogeneous biological tissues with high fluid contents. The experimental shear stress response to sinusoidal translational shear deformation at 1 Hz and 25% strain amplitude and either 0% or 33% compression is compared for rat brain tissue and bovine aortic tissue. Both tissues exhibit Mullins effect in shear. Harmonic wavelet decomposition, a novel application to the mechanical response of these tissues, shows significant 1 Hz and 3 Hz components. The 3 Hz component magnitude in brain tissue, which is much larger than in aortic tissue, may correlate to interstitial fluid induced drag forces that decrease on subsequent cycles perhaps because of damage resulting in easier fluid movement. The fluid may cause the quasiperiodic, viscoelastic behavior of brain tissue. The mechanical response differences under impact may cause shear damage between arterial and brain connections.

  7. Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

    Science.gov (United States)

    Walton, Esther; Hass, Johanna; Liu, Jingyu; Roffman, Joshua L; Bernardoni, Fabio; Roessner, Veit; Kirsch, Matthias; Schackert, Gabriele; Calhoun, Vince; Ehrlich, Stefan

    2016-03-01

    Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.

  8. Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

    Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here....

  9. Automatic Analysis of Brain Tissue and Structural Connectivity in MRI

    NARCIS (Netherlands)

    R. de Boer (Renske)

    2011-01-01

    textabstractStudies of the brain using magnetic resonance imaging (MRI) can provide insights in physiology and pathology that can eventually aid clinical diagnosis and therapy monitoring. MRI data acquired in these studies can be difficult, as well as laborious, to interpret and analyze by human obs

  10. Roles of microglia in brain development, tissue maintenance and repair.

    Science.gov (United States)

    Michell-Robinson, Mackenzie A; Touil, Hanane; Healy, Luke M; Owen, David R; Durafourt, Bryce A; Bar-Or, Amit; Antel, Jack P; Moore, Craig S

    2015-05-01

    The emerging roles of microglia are currently being investigated in the healthy and diseased brain with a growing interest in their diverse functions. In recent years, it has been demonstrated that microglia are not only immunocentric, but also neurobiological and can impact neural development and the maintenance of neuronal cell function in both healthy and pathological contexts. In the disease context, there is widespread consensus that microglia are dynamic cells with a potential to contribute to both central nervous system damage and repair. Indeed, a number of studies have found that microenvironmental conditions can selectively modify unique microglia phenotypes and functions. One novel mechanism that has garnered interest involves the regulation of microglial function by microRNAs, which has therapeutic implications such as enhancing microglia-mediated suppression of brain injury and promoting repair following inflammatory injury. Furthermore, recently published articles have identified molecular signatures of myeloid cells, suggesting that microglia are a distinct cell population compared to other cells of myeloid lineage that access the central nervous system under pathological conditions. Thus, new opportunities exist to help distinguish microglia in the brain and permit the study of their unique functions in health and disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

    Directory of Open Access Journals (Sweden)

    Björn eNitzsche

    2015-06-01

    Full Text Available Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams were acquired on a 1.5T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight, age and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM and white (WM matter as well as cerebrospinal fluid (CSF classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM. Overall, a positive correlation of GM volume and body weight explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species.

  12. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes.

    Science.gov (United States)

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H; Fonov, Vladimir S; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species.

  13. Application of quantitative MRI for brain tissue segmentation at 1.5 T and 3.0 T field strengths.

    Directory of Open Access Journals (Sweden)

    Janne West

    Full Text Available BACKGROUND: Brain tissue segmentation of white matter (WM, grey matter (GM, and cerebrospinal fluid (CSF are important in neuroradiological applications. Quantitative Mri (qMRI allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. METHODS: In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. RESULTS: Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p<0.001. Analyses of main effects showed that WM was underestimated, while GM and CSF were overestimated on 1.5 T compared to 3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. CONCLUSIONS: Most of the brain was identically classified at the two field strengths, although some regional differences were observed.

  14. Prion Protein Deficiency Causes Diverse Proteome Shifts in Cell Models That Escape Detection in Brain Tissue.

    Directory of Open Access Journals (Sweden)

    Mohadeseh Mehrabian

    Full Text Available A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. For the prion protein (PrP, best known for its role in several invariably fatal neurodegenerative diseases, a natural choice, therefore, would be to undertake such studies with brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used. To identify possible causes for this disparity, we set out to systematically investigate the consequence of PrP deficiency on the global proteome in brain tissue and in four distinct cell models. Here we report that PrP deficiency causes robust but surprisingly divergent changes to the global proteomes of cell models but has no discernible impact on the global brain proteome. Amongst >1,500 proteins whose levels were compared in wild-type and PrP-deficient models, members of the MARCKS protein family exhibited pronounced, yet cell model-dependent changes to their steady-state levels. Follow-up experiments revealed that PrP collaborates with members of the MARCKS protein family in its control of NCAM1 polysialylation. We conclude that the physiological function of PrP may be masked in analyses of complex brain samples but its cell-type specific influence on a lipid raft-based NCAM1-related cell biology comes to the fore in investigations of specific cell types.

  15. Dynamic effects of point source electroporation on the rat brain tissue.

    Science.gov (United States)

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, pelectroporation when planning a treatment for brain tumors.

  16. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  17. Frequency-dependent viscoelastic parameters of mouse brain tissue estimated by MR elastography

    Energy Technology Data Exchange (ETDEWEB)

    Clayton, E H; Bayly, P V [Department of Mechanical Engineering and Materials Science, Washington University in St Louis, 1 Brookings Drive, Campus Box 1185, Saint Louis, MO 63130 (United States); Garbow, J R, E-mail: clayton@wustl.edu, E-mail: garbow@wustl.edu, E-mail: pvb@wustl.edu [Biomedical Magnetic Resonance Laboratory, Department of Radiology, Washington University in St Louis, 4525 Scott Avenue, Campus Box 8227, Saint Louis, MO 63110 (United States)

    2011-04-21

    Viscoelastic properties of mouse brain tissue were estimated non-invasively, in vivo, using magnetic resonance elastography (MRE) at 4.7 T to measure the dispersive properties of induced shear waves. Key features of this study include (i) the development and application of a novel MR-compatible actuation system which transmits vibratory motion into the brain through an incisor bar, and (ii) the investigation of the mechanical properties of brain tissue over a 1200 Hz bandwidth from 600-1800 Hz. Displacement fields due to propagating shear waves were measured during continuous, harmonic excitation of the skull. This protocol enabled characterization of the true steady-state patterns of shear wave propagation. Analysis of displacement fields obtained at different frequencies indicates that the viscoelastic properties of mouse brain tissue depend strongly on frequency. The average storage modulus (G') increased from approximately 1.6 to 8 kPa over this range; average loss modulus (G'') increased from approximately 1 to 3 kPa. Both moduli were well approximated by a power-law relationship over this frequency range. MRE may be a valuable addition to studies of disease in murine models, and to pre-clinical evaluations of therapies. Quantitative measurements of the viscoelastic parameters of brain tissue at high frequencies are also valuable for modeling and simulation of traumatic brain injury.

  18. Haloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissue.

    Science.gov (United States)

    Rahmani, Aboubakr; Mohammadpour, Amir Hooshang; Sahebnasagh, Adeleh; Mohajeri, Seyed Ahmad

    2014-11-01

    Several molecularly imprinted polymers (MIPs) were prepared in the present work, and their binding properties were evaluated in comparison with a nonimprinted polymer (NIP). An optimized MIP was selected and applied for selective extraction and analysis of haloperidol in rabbit brain tissue. A molecularly imprinted solid-phase extraction (MISPE) method was developed for cleanup and preconcentration of haloperidol in brain samples before HPLC-UV analysis. Selectivity of the MISPE procedure was investigated using haloperidol and some structurally different drugs with similar polarity that could exist simultaneously in brain tissue. The extraction and analytical process was calibrated in the range of 0.05-10 ppm. The recovery of haloperidol in this MISPE process was calculated between 79.9 and 90.4%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.008 and 0.05 ppm, respectively. Intraday precision and interday precision values for haloperidol analysis were less than 5.86 and 7.63%, respectively. The MISPE method could effectively extract and concentrate haloperidol from brain tissue in the presence of clozapine and imipramine. Finally, the imprinted polymer was successfully applied for the determination of haloperidol in a real rabbit brain sample after administration of a toxic dose. Therefore, the proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of haloperidol in rabbit brain tissue.

  19. Three-dimensional structure of brain tissue at submicrometer resolution

    Science.gov (United States)

    Saiga, Rino; Mizutani, Ryuta; Inomoto, Chie; Takekoshi, Susumu; Nakamura, Naoya; Tsuboi, Akio; Osawa, Motoki; Arai, Makoto; Oshima, Kenichi; Itokawa, Masanari; Uesugi, Kentaro; Takeuchi, Akihisa; Terada, Yasuko; Suzuki, Yoshio

    2016-01-01

    Biological objects are composed of submicrometer structures such as cells and organelles that are essential for their functions. Here, we report on three-dimensional X-ray visualization of cells and organelles at resolutions up to 100 nm by imaging microtomography (micro-CT) equipped with Fresnel zone plate optics. Human cerebral tissue, fruit fly cephalic ganglia, and Escherichia coli bacteria labeled with high atomic-number elements were embedded in epoxy resin and subjected to X-ray microtomography at the BL37XU and BL47XU beamlines of the SPring-8 synchrotron radiation facility. The obtained results indicated that soft tissue structures can be visualized with the imaging microtomography.

  20. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Young, E-mail: eyhan@uams.edu [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Moros, Eduardo [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL (United States); Corry, Peter [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  1. Trace element determinations in brain tissues from normal and clinically demented individuals

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Genezini, Frederico A., E-mail: mitiko@ipen.br, E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisas; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson, E-mail: renataleite@usp.br, E-mail: lea@grinberg.com.br, E-mail: reloah@usp.br, E-mail: farfel@usp.br, E-mail: csuemoto@gmail.com, E-mail: cpasqua@usp.br, E-mail: wijac@usp.br [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2013-07-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  2. Accuracy of a Wearable Sensor for Measures of Head Kinematics and Calculation of Brain Tissue Strain.

    Science.gov (United States)

    Knowles, Brooklynn M; Yu, Henry; Dennison, Christopher R

    2017-02-01

    Wearable kinematic sensors can be used to study head injury biomechanics based on kinematics and, more recently, based on tissue strain metrics using kinematics-driven brain models. These sensors require in-situ calibration and there is currently no data conveying wearable ability to estimate tissue strain. We simulated head impact (n = 871) to a 50th percentile Hybrid III (H-III) head wearing a hockey helmet instrumented with wearable GForceTracker (GFT) sensors measuring linear acceleration and angular velocity. A GFT was also fixed within the H-III head to establish a lower boundary on systematic errors. We quantified GFT errors relative to H-III measures based on peak kinematics and cumulative strain damage measure (CSDM). The smallest mean errors were 12% (peak resultant linear acceleration) and 15% (peak resultant angular velocity) for the GFT within the H-III. Errors for GFTs on the helmet were on average 54% (peak resultant linear acceleration) and 21% (peak resultant angular velocity). On average, the GFT inside the helmet overestimated CSDM by 0.15.

  3. Optical properties of mouse brain tissue after optical clearing with FocusClear™

    Science.gov (United States)

    Moy, Austin J.; Capulong, Bernard V.; Saager, Rolf B.; Wiersma, Matthew P.; Lo, Patrick C.; Durkin, Anthony J.; Choi, Bernard

    2015-09-01

    Fluorescence microscopy is commonly used to investigate disease progression in biological tissues. Biological tissues, however, are strongly scattering in the visible wavelengths, limiting the application of fluorescence microscopy to superficial (brain after optical clearing with FocusClear™. Light transmittance and reflectance of 1-mm mouse brain sections were measured using an integrating sphere before and after optical clearing and the inverse adding doubling algorithm used to determine tissue optical scattering. The degree of optical clearing was quantified by calculating the optical clearing potential (OCP), and the effects of differing OCP were demonstrated using the optical histology method, which combines tissue optical clearing with optical imaging to visualize the microvasculature. We observed increased tissue transparency with longer optical clearing time and an analogous increase in OCP. Furthermore, OCP did not vary substantially between 400 and 1000 nm for increasing optical clearing durations, suggesting that optical histology can improve ex vivo visualization of several fluorescent probes.

  4. Tissue motion and strain in the human brain assessed by intraoperative ultrasound in glioma patients.

    Science.gov (United States)

    Selbekk, Tormod; Brekken, Reidar; Solheim, Ole; Lydersen, Stian; Hernes, Toril A N; Unsgaard, Geirmund

    2010-01-01

    The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p=0.163 to p=0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p=0.0004) and for the two regions further away from the tumor border (p=0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

  5. Imaging extracellular potassium dynamics in brain tissue using a potassium-sensitive nanosensor.

    Science.gov (United States)

    Wellbourne-Wood, Joel; Rimmele, Theresa S; Chatton, Jean-Yves

    2017-01-01

    Neuronal activity results in the release of [Formula: see text] into the extracellular space (ECS). Classically, measurements of extracellular [Formula: see text] ([Formula: see text]) are carried out using [Formula: see text]-sensitive microelectrodes, which provide a single point measurement with undefined spatial resolution. An imaging approach would enable the spatiotemporal mapping of [Formula: see text]. Here, we report on the design and characterization of a fluorescence imaging-based [Formula: see text]-sensitive nanosensor for the ECS based on dendrimer nanotechnology. Spectral characterization, sensitivity, and selectivity of the nanosensor were assessed by spectrofluorimetry, as well as in both wide-field and two-photon microscopy settings, demonstrating the nanosensor efficacy over the physiologically relevant ion concentration range. Spatial and temporal kinetics of the nanosensor responses were assessed using a localized iontophoretic [Formula: see text] application on a two-photon imaging setup. Using acute mouse brain slices, we demonstrate that the nanosensor is retained in the ECS for extended periods of time. In addition, we present a ratiometric version of the nanosensor, validate its sensitivity in brain tissue in response to elicited neuronal activity and correlate the responses to the extracellular field potential. Together, this study demonstrates the efficacy of the [Formula: see text]-sensitive nanosensor approach and validates the possibility of creating multimodal nanosensors.

  6. Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue.

    Science.gov (United States)

    Nakielski, Paweł; Kowalczyk, Tomasz; Zembrzycki, Krzysztof; Kowalewski, Tomasz A

    2015-02-01

    Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing.

  7. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  8. White matter segmentation by estimating tissue optical attenuation from volumetric OCT massive histology of whole rodent brains

    Science.gov (United States)

    Lefebvre, Joël.; Castonguay, Alexandre; Lesage, Frédéric

    2017-02-01

    A whole rodent brain was imaged using an automated massive histology setup and an Optical Coherence Tomography (OCT) microscope. Thousands of OCT volumetric tiles were acquired, each covering a size of about 2.5x2.5x0.8 mm3 with a sampling resolution of 4.9x4.9x6.5 microns. This paper shows the techniques for reconstruction, attenuation compensation and segmentation of the sliced brains. The tile positions within the mosaic were evaluated using a displacement model of the motorized stage and pairwise coregistration. Volume blending was then performed by solving the 3D Laplace equation, and consecutive slices were assembled using the cross-correlation of their 2D image gradient. This reconstruction algorithm resulted in a 3D map of optical reflectivity for the whole brain at micrometric resolution. OCT tissue slices were then used to estimate the local attenuation coefficient based on a single scattering photon model. The attenuation map obtained exhibits a high contrast for all white matter fibres, regardless of their orientation. The tissue optical attenuation from the intrinsic OCT reflectivity contributes to better white matter tissue segmentation. The combined 3D maps of reflectivity and attenuation is a step toward the study of white matter at a microscopic scale for the whole brain in small animals.

  9. Investigation on metal elements in the brain tissues from DNTC patients

    Energy Technology Data Exchange (ETDEWEB)

    Ide-Ektessabi, Ari E-mail: h51167@sakura.kudpc.kyoto-u.ac.jp; Kawakami, Takuo; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

    2004-07-01

    Trace metallic elements in human cells play important roles in various cell functions as metalloprotein, metalloenzyme or metallic ions. Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles without senile plaques. In this study, X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) was applied to determine the distribution and density of the ultra-trace elements in the brain tissues from DTNC patients. This method made it possible to determine trace metallic elements non-destructively. The trace metallic elements (such as Ca, Fe, Zn, and Pb) in the brain tissues were examined. Two-dimension imaging of the elements and relative quantification of the elements in the brains were performed. The lead concentrations were observed in the calcified blood vessel in the brains with DNTC.

  10. The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research.

    Science.gov (United States)

    Sutherland, G T; Sheedy, D; Stevens, J; McCrossin, T; Smith, C C; van Roijen, M; Kril, J J

    2016-05-01

    The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections.

  11. Features of microelement maintenance in rat's brain tissues at experimental hypoxia of different degree.

    Directory of Open Access Journals (Sweden)

    Tarasova I.V.

    2011-01-01

    Full Text Available Features of microelement maintenance (iron, zinc, copper, manganese, and cobalt, conditionally toxic chrome and toxic lead were studied in newborn rat's brain tissues at experimental hypoxia of different degree. Tissues of newborn rat’s brain are characterized by high level of saturation and considerable dynamism of microelement maintenance. Till the end of the first week of life, the maintenance of these microelements decreases in 1,5 – 10 times. The level of the toxic lead decreases more than in 2,5 times. The hypoxia of easy degree of newborn rats invokes reduction cobalt level 3 times, iron level 2 times, manganese – on 27,65 %, chrome – on 25,84%, zinc – on 16,43%. It means that considerable deficiency and disbalance of microelement maintenance rat's brain tissues. The heavy degree of hypoxia is characterized by further increase of deficiency and disbalance of microelements.

  12. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats

    Institute of Scientific and Technical Information of China (English)

    Erukainure OL; Ajiboye JA; Adejobi RO; Okafor OY; Kosoko SB; Owolabi FO

    2011-01-01

    Objective:To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Methods:Oxidative stress was induced by oral administration of ethanol (20%w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Results:Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Conclusions:Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.

  13. Frequency dependence of complex moduli of brain tissue using a fractional Zener model

    Energy Technology Data Exchange (ETDEWEB)

    Kohandel, M [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Sivaloganathan, S [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Tenti, G [Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Darvish, K [Center for Applied Biomechanics, University of Virginia, Charlottesville, VA (United States)

    2005-06-21

    Brain tissue exhibits viscoelastic behaviour. If loading times are substantially short, static tests are not sufficient to determine the complete viscoelastic behaviour of the material, and dynamic test methods are more appropriate. The concept of complex modulus of elasticity is a powerful tool for characterizing the frequency domain behaviour of viscoelastic materials. On the other hand, it is well known that classical viscoelastic models can be generalized by means of fractional calculus to describe more complex viscoelastic behaviour of materials. In this paper, the fractional Zener model is investigated in order to describe the dynamic behaviour of brain tissue. The model is fitted to experimental data of oscillatory shear tests of bovine brain tissue to verify its behaviour and to obtain the material parameters.

  14. Reactive microglia specifically associated with amyloid plaques in Alzheimer's disease brain tissue express melanotransferrin.

    Science.gov (United States)

    Jefferies, W A; Food, M R; Gabathuler, R; Rothenberger, S; Yamada, T; Yasuhara, O; McGeer, P L

    1996-03-11

    Several investigations have implicated the involvement of metals in neuropathologies. In particular, the disruption of iron metabolism and iron transport molecules have been demonstrated in Alzheimer's disease (AD). We have identified a novel pathway of iron uptake into mammalian cells involving melanotransferrin, or p97, which is independent of the transferrin receptor. Here we investigated whether there is a possible link between this molecule and the pathology of AD. The distributions of melanotransferrin, transferrin and the transferrin receptor were studied immunohistochemically in brain tissues from AD cases. In brain tissues from AD, melanotransferrin and the transferrin receptor were highly localized to capillary endothelium, while transferrin itself was mainly localized to glial cells. In brain tissue derived from AD patients, melanotransferrin was additionally detected in a subset of reactive microglia associated with senile plaques. Our demonstration that melanotransferrin mediates iron uptake through a pathway independent of the transferrin receptor indicates that this mechanism may have a role in AD.

  15. Three-dimensional structure of brain tissue at submicrometer resolution

    Energy Technology Data Exchange (ETDEWEB)

    Saiga, Rino; Mizutani, Ryuta, E-mail: ryuta@tokai-u.jp [Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292 (Japan); Inomoto, Chie; Takekoshi, Susumu; Nakamura, Naoya; Tsuboi, Akio; Osawa, Motoki [Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Arai, Makoto; Oshima, Kenichi; Itokawa, Masanari [Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506 (Japan); Uesugi, Kentaro; Takeuchi, Akihisa; Terada, Yasuko; Suzuki, Yoshio [Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), Sayo, Hyogo 679-5198 (Japan)

    2016-01-28

    Biological objects are composed of submicrometer structures such as cells and organelles that are essential for their functions. Here, we report on three-dimensional X-ray visualization of cells and organelles at resolutions up to 100 nm by imaging microtomography (micro-CT) equipped with Fresnel zone plate optics. Human cerebral tissue, fruit fly cephalic ganglia, and Escherichia coli bacteria labeled with high atomic-number elements were embedded in epoxy resin and subjected to X-ray microtomography at the BL37XU and BL47XU beamlines of the SPring-8 synchrotron radiation facility. The obtained results indicated that soft tissue structures can be visualized with the imaging microtomography.

  16. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  17. High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

    Science.gov (United States)

    Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

    2005-01-01

    Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

  18. Protective effects of acupuncture on brain tissue following ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Mingshan Wang; Fuguo Ma; Huailong Chen

    2008-01-01

    BACKGROUND: In patients with cerebrovascular disease, by means of the neuroendocrine system, acupuncture supports the transformation of a local pathological status into a physiological status. Recently, great progress has been made in studying the protective effects of acupuncture on brain ischemia/reperfusion injury. OBJECTIVE: To summarize research advances in the protective effects of acupuncture on brain ischemia/reperfusion injury. RETRIEVAL STRATEGY: Using the terms "acupuncture, transcutaneous electrical acupoint stimulation, cerebral ischemia/reperfusion injury, and cerebral protection", we retrieved articles from the PubMed database published between January 1991 and June 1994. Meanwhile, we searched the China National Knowledge Infrastructure with the same terms. Altogether, 114 articles and their results were analyzed. Inclusive criteria: studies that were closely related to the protective effects of acupuncture on brain ischemia/reperfusion injury, or studies, whose contents were in the same study field and were published recently, or in the authorized journals. Exclusive criteria: repetitive studies. LITERATURE EVALUATION: Thirty articles that related to the protective effects of acupuncture on brain ischemia/reperfusion injury were included. Among them, 7 were clinical studies, and the remaining 23 articles were animal experimental studies. DATA SYNTHESIS: ① Animal experimental studies have demonstrated that acupuncture improves brain blood perfusion and brain electrical activity, influences pathomorphological and ultramicrostructural changes in ischemic brain tissue, is beneficial in maintaining the stability of intracellular and extracellular ions, resists free radical injury and lipid peroxidation, and influences cytokine, neurotransmitter, brain cell signal transduction, and apoptosis-regulating genes. ② Clinical studies have demonstrated that acupuncture not only promotes nutritional supply to local brain tissue in patients with cerebral

  19. A low background Raman probe for optical biopsy of brain tissue

    Science.gov (United States)

    Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Day, John C.

    2014-03-01

    Removal of intrinsic brain tumours is a delicate process, where a high degree of specificity is required to remove all of the tumour tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200mm and inner diameter of 1.8mm. The probe achieves a very low fluorescent background whilst maintaining good collection of Raman signal by employing a miniature stand-off Raman design. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibres for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the fluorescence caused by silica fibres in a Raman needle probe is reduced by a factor of two for Raman shifts under 500 cm-1, and by 30% at 600-700 cm-1. In addition, this design contains only medically approved materials at the distal end. The probe's suitability for use on tissue is demonstrated by discriminating between different types of porcine brain tissue.

  20. Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

    Science.gov (United States)

    Bonar, Nicolle A; Petersen, Christian P

    2017-03-01

    Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema.

  1. Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

    Science.gov (United States)

    Ronsoni, Marcelo Fernando; Remor, Aline Pertile; Lopes, Mark William; Hohl, Alexandre; Troncoso, Iris H Z; Leal, Rodrigo Bainy; Boos, Gustavo Luchi; Kondageski, Charles; Nunes, Jean Costa; Linhares, Marcelo Neves; Lin, Kátia; Latini, Alexandra Susana; Walz, Roger

    2016-04-01

    Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

  2. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Renata Francik

    2014-01-01

    Full Text Available Cornelian cherry (Cornus mas is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer’s disease or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet. This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  3. Profile analysis of hepatic porcine and murine brain tissue slices obtained with a vibratome.

    Science.gov (United States)

    Mattei, G; Cristiani, I; Magliaro, C; Ahluwalia, A

    2015-01-01

    This study is aimed at characterizing soft tissue slices using a vibratome. In particular, the effect of two sectioning parameters (i.e., step size and sectioning speed) on resultant slice thickness was investigated for fresh porcine liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A simple framework for embedding, sectioning and imaging the slices was established to derive their thickness, which was evaluated through a purposely developed graphical user interface. Sectioning speed and step size had little effect on the thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine brain slices was found to be dependent on the step size, but not on the sectioning speed. In view of these results, fresh brain tissue was sliced varying the step size only, which was found to have a significant effect on resultant slice thickness. Although precision-cut slices (i.e., with regular thickness) were obtained for all the tissues, slice accuracy (defined as the match between the nominal step size chosen and the actual slice thickness obtained) was found to increase with tissue stiffness from fresh liver to PFA-fixed brain. This quantitative investigation can be very helpful for establishing the most suitable slicing setup for a given tissue.

  4. 65zinc uptake from blood into brain and other tissues in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. (Sunderland Polytechnic, Tyne Wear (England))

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  5. Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

    Science.gov (United States)

    Johnson, Lee James

    2001-08-01

    The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

  6. Changes in brain tissue and behavior patterns induced by single short-term fasting in mice.

    Directory of Open Access Journals (Sweden)

    Yuko Hisatomi

    Full Text Available In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.

  7. Changes in brain tissue and behavior patterns induced by single short-term fasting in mice.

    Science.gov (United States)

    Hisatomi, Yuko; Asakura, Kyo; Kugino, Kenji; Kurokawa, Mamoru; Asakura, Tomiko; Nakata, Keiko

    2013-01-01

    In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.

  8. Brain-Science Based Cohort Studies

    Science.gov (United States)

    Koizumi, Hideaki

    2011-01-01

    This article describes a number of human cohort studies based on the concept of brain-science and education. These studies assess the potential effects of new technologies on babies, children and adolescents, and test hypotheses drawn from animal and genetic case studies to see if they apply to people. A flood of information, virtual media,…

  9. Brain-Science Based Cohort Studies

    Science.gov (United States)

    Koizumi, Hideaki

    2011-01-01

    This article describes a number of human cohort studies based on the concept of brain-science and education. These studies assess the potential effects of new technologies on babies, children and adolescents, and test hypotheses drawn from animal and genetic case studies to see if they apply to people. A flood of information, virtual media,…

  10. Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion.

    Science.gov (United States)

    Bivard, A; Levi, C; Krishnamurthy, V; Hislop-Jambrich, J; Salazar, P; Jackson, B; Davis, S; Parsons, M

    2014-12-01

    This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements. One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6hours of acute stroke onset, followed by 24hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds. For single perfusion thresholds, a time to peak (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74-0.83) while a cerebral blood flow (CBF) of acute ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83-0.87) and was significantly closer in volume to the corresponding reference DWI (P=0.031). Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Tissue concentration of systemically administered antineoplastic agents in human brain tumors

    Science.gov (United States)

    Desai, Arati; Grossman, Stuart A.; Blakeley, Jaishri O.

    2014-01-01

    The blood–brain-barrier (BBB) limits the penetration of many systemic antineoplastic therapies. Consequently, many agents may be used in clinical studies and clinical practice though they may not achieve therapeutic levels within the tumor. We sought to compile the currently available human data on antineoplastic drug concentrations in brain and tumor tissue according to BBB status. A review of the literature was conducted for human studies providing concentrations of antineoplastic agents in blood and metastatic brain tumors or high-grade gliomas. Studies were considered optimal if they reported simultaneous tissue and blood concentration, multiple sampling times and locations, MRI localization, BBB status at sampling site, tumor histology, and individual subject data. Twenty-Four studies of 19 compounds were included. These examined 18 agents in contrast-enhancing regions of high-grade gliomas, with optimal data for 2. For metastatic brain tumors, adequate data was found for 9 agents. Considerable heterogeneity was found in the measurement value, tumor type, measurement timing, and sampling location within and among studies, limiting the applicability of the results. Tissue to blood ratios ranged from 0.054 for carboplatin to 34 for mitoxantrone in high-grade gliomas, and were lowest for temozolomide (0.118) and etoposide (0.116), and highest for mitoxantrone (32.02) in metastatic tumors. The available data examining the concentration of antineoplastic agents in brain and tumor tissue is sparse and limited by considerable heterogeneity. More studies with careful quantification of antineoplastic agents in brain and tumor tissue is required for the rational development of therapeutic regimens. PMID:21400119

  12. Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

    Science.gov (United States)

    Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

    2017-03-01

    The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET

  13. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  14. Study into penetration speed during laser cutting of brain tissues.

    Science.gov (United States)

    Yilbas, Z; Sami, M; Patiroglu, T

    1998-01-01

    The applications of CO2 continuous-wave lasers in neurosurgery have become important in recent years. Theoretical considerations of laser applicability in medicine are subsequently confirmed experimentally. To obtain precision operation in the laser cutting process, further theoretical developments and experimental studies need to be conducted. Consequently, in the present study, the heat transfer mechanism taking place during laser-tissue interaction is introduced using Fourier theory. The results obtained from the theoretical model are compared with the experimental results. In connection with this, an experiment is designed to measure the penetration speed during the laser cutting process. The measurement is carried out using an optical method. It is found that both results for the penetration speed obtained from the theory and experiment are in a good agreement.

  15. Quantitative analysis of sodium fast and slow component in in vivo human brain tissue using MR Na image

    Energy Technology Data Exchange (ETDEWEB)

    Hirai, Hirokazu; Yamasaki, Katsuhito; Kidena, Hitoshi; Kono, Michio (Kobe Univ. (Japan). School of Medicine)

    1992-12-01

    In vivo sodium concentrations in the normal brain tissue and a tumorous tissue were analyzed using MR Na image. The nuclear magnetic resonance enabled us to divide the signal from sodium in the living tissue into 2 parts based on the differences of T[sub 2] value. Those are fast component having the T[sub 2] value of less than 5 msec and slow component of 15-40 msec. We investigated the effect of macromolecules on T[sub 2] value of sodium image using polyvinylalcohol (PVA) powder. MR Na image was taken with the parameters of TR/TD, 110 ms/1.9 ms (FID image) and TR/TE, 110 ms/20 ms (SE image). Saline solution showed high intensity on both FID image and SE image. Saline solution added PVA (PVA phantom) also showed high intensity on FID image, whereas the signal intensity of PVA phantom in SE image extinguished. To know the relation between the signal intensity and sodium concentration, sodium concentration-signal intensity curve was obtained using phantoms with various sodium concentrations (0.05-1.0%). This curve showed a direct proportion between sodium concentration and signal intensity on Na image. We measured further the sodium concentrations of the human brain tissue. Sodium phantoms were arranged around the heads and the MR Na images of the normal brains from 3 volunteers and a patient with a brain tumor (meningioma) were taken. The sodium concentrations of occipital lobe, basal ganglia and the tumorous tissue were calculated using the sodium concentration-signal intensity curve obtained from the phantoms arranged around the heads. Two tailed t-test shows significant differences (p<0.01) in total sodium and slow component between occipital lobe and basal ganglia. Further more high concentration of fast component in tumorous tissue was observed. As fast component reflects the intracellular condition, present experiments suggest that measurement of fast component may be useful for obtaining the functional information of the brain tissue. (author).

  16. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  17. Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2011-02-01

    A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.

  18. Effect of Oxytropis glabra DC. Poisoning on α-Mannosidase(AMA) Expression in Mice Brain Tissue

    Institute of Scientific and Technical Information of China (English)

    Wang Shuai; Jia Qizhen; Zhang Ling; Chen Genyuan; Ma Chunhui

    2015-01-01

    The effect of Oxytropis glabra DC. on α-mannosidase( AMA) expression in mice brain tissue was explored to reveal the toxicity mechanism of O. glabra. Forty mice were randomly divided into four groups,namely control group,experimental group I,experimental group II and experimental group III. The mice in three experimental groups were fed with O. glabra at the doses of 1,5 and 10 g per kilogram weight,respectively. After challenge for 63 d,mice brains were collected to detect changes in distribution and expression of AMA in different brain regions. The results showed that O. glabra poisoning led to declined AMA mRNA expression in mice brain tissue,but the mice in experimental group I had no significant difference with those in control group( P > 0. 05). The AMA mRNA expression in cerebellum,cerebrum and thalamus of mice in experimental groups II and III were significantly lower than that in control group( P 0. 05). AMA had very weak expression in hippocampus and brainstem,but it had expressions in other regions,and the expression was positively correlated with the number of neurons and granulosa cells. The results showed that different doses of O. glabra reduced AMA mRNA expression in mice brain tissue,while cerebellum,cerebrum and thalamus were the main target function areas.

  19. Diazepam binding inhibitor gene expression: Location in brain and peripheral tissues of rate

    Energy Technology Data Exchange (ETDEWEB)

    Alho, H.; Fremeau, R.T. Jr.; Tiedge, H.; Wilcox, J.; Bovolin, P.; Brosius, J.; Roberts, J.L.; Costa, E.

    1988-09-01

    Diazepam binding inhibitor (DBI), an endogenous 10-kDa polypeptide was isolated from rat and human brain by monitoring displacement of radioactive diazepam bound to specific recognition sites in brain synaptic and mitochondrial membranes. The cellular location of DBI mRNA was studied in rat brain and selected peripheral tissues by in situ hybridization histochemistry with a /sup 35/S-labeled single-stranded complementary RNA probe. DBI mRNA was heterogeneously distributed in rat brain, with particularly high levels in the area postrema, the cerebellar cortex, and ependyma of the third ventricle. Intermediate levels were found in the olfactory bulb, pontine nuclei, inferior colliculi, arcuate nucleus, and pineal gland. Relatively low but significant levels of silver grains were observed overlying many mesencephalic and telencephalic areas that have previously been shown to contain numerous DBI-immunoreactive neurons and a high density of central benzodiazepine receptors. In situ hybridizations also revealed high levels of DBI mRNA in the posterior lobe of the pituitary gland, liver, and germinal center of the white pulp of spleen, all tissues that are rich in peripheral benzodiazepine binding sites. The tissue-specific pattern of DBI gene expression described here could be exploited to further understand the physiological function of DBI in the brain and periphery.

  20. Genomic imprinting variations in the mouse type 3 deiodinase gene between tissues and brain regions.

    Science.gov (United States)

    Martinez, M Elena; Charalambous, Marika; Saferali, Aabida; Fiering, Steven; Naumova, Anna K; St Germain, Donald; Ferguson-Smith, Anne C; Hernandez, Arturo

    2014-11-01

    The Dio3 gene, which encodes for the type 3 deiodinase (D3), controls thyroid hormone (TH) availability. The lack of D3 in mice results in tissue overexposure to TH and a broad neuroendocrine phenotype. Dio3 is an imprinted gene, preferentially expressed from the paternally inherited allele in the mouse fetus. However, heterozygous mice with paternal inheritance of the inactivating Dio3 mutation exhibit an attenuated phenotype when compared with that of Dio3 null mice. To investigate this milder phenotype, the allelic expression of Dio3 was evaluated in different mouse tissues. Preferential allelic expression of Dio3 from the paternal allele was observed in fetal tissues and neonatal brain regions, whereas the biallelic Dio3 expression occurred in the developing eye, testes, and cerebellum and in the postnatal brain neocortex, which expresses a larger Dio3 mRNA transcript. The newborn hypothalamus manifests the highest degree of Dio3 expression from the paternal allele, compared with other brain regions, and preferential allelic expression of Dio3 in the brain relaxed in late neonatal life. A methylation analysis of two regulatory regions of the Dio3 imprinted domain revealed modest but significant differences between tissues, but these did not consistently correlate with the observed patterns of Dio3 allelic expression. Deletion of the Dio3 gene and promoter did not result in significant changes in the tissue-specific patterns of Dio3 allelic expression. These results suggest the existence of unidentified epigenetic determinants of tissue-specific Dio3 imprinting. The resulting variation in the Dio3 allelic expression between tissues likely explains the phenotypic variation that results from paternal Dio3 haploinsufficiency.

  1. Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography

    NARCIS (Netherlands)

    Jansen, H M; Pruim, J; vd Vliet, A M; Paans, A M; Hew, J M; Franssen, E J; de Jong, B M; Kosterink, J G; Haaxma, R; Korf, J

    1994-01-01

    UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+ i

  2. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    1998-01-01

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118

  3. Are brain and heart tissue prone to the development of thiamine deficiency?

    NARCIS (Netherlands)

    Klooster, Astrid; Larkin, James R.; Wiersema-Buist, Janneke; Gans, Reinold O. B.; Thornalley, Paul J.; Navis, Gerjan; van Goor, Harry; Leuvenink, Henri G. D.; Bakker, Stephan J. L.

    2013-01-01

    Thiamine deficiency is a continuing problem leading to beriberi and Wernicke's encephalopathy. The symptoms of thiamine deficiency develop in the heart, brain and neuronal tissue. Yet, it is unclear how rapid thiamine deficiency develops and which organs are prone to development of thiamine deficien

  4. Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard.

    NARCIS (Netherlands)

    Pirman, D.A.; Reich, R.F.; Kiss, A.; Heeren, R.M.A.; Yost, R.A.

    2013-01-01

    Mass spectrometric imaging (MSI) is an analytical technique used to determine the distribution of individual analytes within a given sample. A wide array of analytes and samples can be investigated by MSI, including drug distribution in rats, lipid analysis from brain tissue, protein differentiation

  5. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Lauriane Jugé

    Full Text Available Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both, an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM and rearrangement of the cortical gray matter microstructure (P < 0.001, for both, while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both. During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001, while a decrease in space was observed for the ventral internal capsule (P < 0.001. For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001. To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions

  6. Exercise induces autophagy in peripheral tissues and in the brain.

    Science.gov (United States)

    He, Congcong; Sumpter, Rhea; Levine, Beth

    2012-10-01

    We recently identified physical exercise as a newly defined inducer of autophagy in vivo. Exercise induced autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. To study the physiological role of exercise-induced autophagy, we generated mice with a knock-in nonphosphorylatable mutation in BCL2 (Thr69Ala, Ser70Ala and Ser84Ala) (BCL2 AAA) that are defective in exercise- and starvation-induced autophagy but not in basal autophagy. We found that BCL2 AAA mice could not run on a treadmill as long as wild-type mice, and did not undergo exercise-mediated increases in skeletal glucose muscle uptake. Unlike wild-type mice, the BCL2 AAA mice failed to reverse high-fat diet-induced glucose intolerance after 8 weeks of exercise training, possibly due to defects in signaling pathways that regulate muscle glucose uptake and metabolism during exercise. Together, these findings suggested a hitherto unknown important role of autophagy in mediating exercise-induced metabolic benefits. In the present addendum, we show that treadmill exercise also induces autophagy in the cerebral cortex of adult mice. This observation raises the intriguing question of whether autophagy may in part mediate the beneficial effects of exercise in neurodegeneration, adult neurogenesis and improved cognitive function.

  7. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    Science.gov (United States)

    Ishihara, R.; Hanaichi, T.; Takeuchi, T.; Ektessabi, A. M.

    1999-06-01

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  8. A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy.

    Science.gov (United States)

    Rejmstad, Peter; Johansson, Johannes D; Haj-Hosseini, Neda; Wårdell, Karin

    2017-03-01

    Continuous measurement of local brain oxygen saturation (SO2 ) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the "gold standard" in measuring cerebral oxygen pressure (pO2 ), which is closely related to SO2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO2 for different blood concentrations. The P3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO2 . The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5-2%) where pO2 and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile.

  9. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

    Full Text Available The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  10. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion.

    Science.gov (United States)

    Polanco, Michael; Bawab, Sebastian; Yoon, Hargsoon

    2016-06-16

    The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  11. Dynamical properties of the brain tissue under oscillatory shear stresses at large strain range

    Science.gov (United States)

    Boudjema, F.; Khelidj, B.; Lounis, M.

    2017-01-01

    In this experimental work, we study the viscoelastic behaviour of in vitro brain tissue, particularly the white matter, under oscillatory shear strain. The selective vulnerability of this tissue is the anisotropic mechanical properties of theirs different regions lead to a sensitivity to the angular shear rate and magnitude of strain. For this aim, shear storage modulus (G‧) and loss modulus (G″) were measured over a range of frequencies (1 to 100 Hz), for different levels of strain (1 %, to 50 %). The mechanical responses of the brain matter samples showed a viscoelastic behaviour that depend on the correlated strain level and frequency range and old age sample. The samples have been showed evolution behaviour by increasing then decreasing the strain level. Also, the stiffness anisotropy of brain matter was showed between regions and species.

  12. A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

    Science.gov (United States)

    Takatori, T; Tomii, S; Terazawa, K; Nagao, M; Kanamori, M; Tomaru, Y

    1991-01-01

    The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

  13. Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue

    DEFF Research Database (Denmark)

    Petersen, G.; Moesgaard, B.; Hansen, Harald S.

    2005-01-01

    The endogenous levels of the two cannabinoid receptor ligands 2-arachidonoyl glycerol and anandamide, and their respective congeners, monoacyl glycerols and N-acylethanolamines, as well as the phospholipid precursors of N-acylethanolamines, were measured by gas chromatography-mass spectrometry in...... in glioblastoma (WHO grade IV) tissue and meningioma (WHO grade I) tissue and compared with human non-tumour brain tissue. Furthermore, the metabolic turnover of N-acylethanolamines was compared by measurements of the enzymatic activity of N-acyltransferase, N...

  14. Nonlocal correlations of polarization-entangled photons through brain tissue (Conference Presentation)

    Science.gov (United States)

    Galvez, Enrique J.; Shi, Lingyan; Alfano, Robert R.

    2017-02-01

    We investigated the preservation of non-local correlations between polarization-entangled photons when one of them traveled through brain tissue slices of different thicknesses. Using down-converted photons at a wavelength of 802 nm minimized the absorption by the tissue. After the light passed through the tissue samples, we performed quantum state tomography to obtain quantitative measures of the entanglement. We found that entanglement is preserved to a surprising degree, and when it degrades, it does so following a particular path in a tangle versus linear-entropy graph. Such a trajectory reveals direct transfer of probability from entangled to mixed state.

  15. Realistic Numerical and Analytical Modeling of Light Scattering in Brain Tissue for Optogenetic Applications(1,2,3).

    Science.gov (United States)

    Yona, Guy; Meitav, Nizan; Kahn, Itamar; Shoham, Shy

    2016-01-01

    In recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka-Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings. Here, we introduce and study two modified approaches for modeling the distributions of light emanating from a multimode fiber and scattering through tissue, using both realistic numerical Monte Carlo simulations and an analytical approach based on the beam-spread function approach. We demonstrate a good agreement of the new methods' predictions both with recently published data, and with new measurements in mouse brain cortical slices, where our results yield a new cortical scattering length estimate of ∼47 µm at λ = 473 nm, significantly shorter than ordinarily assumed in optogenetic applications.

  16. Carcinoma cells misuse the host tissue damage response to invade the brain

    Science.gov (United States)

    Chuang, Han-Ning; van Rossum, Denise; Sieger, Dirk; Siam, Laila; Klemm, Florian; Bleckmann, Annalen; Bayerlová, Michaela; Farhat, Katja; Scheffel, Jörg; Schulz, Matthias; Dehghani, Faramarz; Stadelmann, Christine; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. PMID:23832647

  17. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

    Science.gov (United States)

    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. © 2016 International Society for Neurochemistry.

  18. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    Science.gov (United States)

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    Distributed microelectrode array (MEA) recordings from consistent, viable, ≥500 μm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3-D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step toward the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long) brain slice preparations. PMID:27065793

  19. Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke.

    Science.gov (United States)

    Wang, Yuanfei; Cooke, Michael J; Sachewsky, Nadia; Morshead, Cindi M; Shoichet, Molly S

    2013-11-28

    Stroke is a leading cause of disability with no effective regenerative treatment. One promising strategy for achieving tissue repair involves the stimulation of endogenous neural stem/progenitor cells through sequential delivery of epidermal growth factor (EGF) followed by erythropoietin (EPO). Yet currently available delivery strategies such as intracerebroventricular (ICV) infusion cause significant tissue damage. We designed a novel delivery system that circumvents the blood brain barrier and directly releases growth factors to the brain. Sequential release of the two growth factors is a key in eliciting tissue repair. To control release, we encapsulate pegylated EGF (EGF-PEG) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles and EPO in biphasic microparticles comprised of a PLGA core and a poly(sebacic acid) coating. EGF-PEG and EPO polymeric particles are dispersed in a hyaluronan methylcellulose (HAMC) hydrogel which spatially confines the particles and attenuates the inflammatory response of brain tissue. Our composite-mediated, sequential delivery of EGF-PEG and EPO leads to tissue repair in a mouse stroke model and minimizes damage compared to ICV infusion.

  20. In vitro-differentiated neural cell cultures progress towards donor-identical brain tissue

    Science.gov (United States)

    Hjelm, Brooke E.; Salhia, Bodour; Kurdoglu, Ahmet; Szelinger, Szabolcs; Reiman, Rebecca A.; Sue, Lucia I.; Beach, Thomas G.; Huentelman, Matthew J.; Craig, David W.

    2013-01-01

    Multiple research groups have observed neuropathological phenotypes and molecular symptoms in vitro using induced pluripotent stem cell (iPSC)-derived neural cell cultures (i.e. patient-specific neurons and glia). However, the global differences/similarities that may exist between in vitro neural cells and their tissue-derived counterparts remain largely unknown. In this study, we compared temporal series of iPSC-derived in vitro neural cell cultures to endogenous brain tissue from the same autopsy donor. Specifically, we utilized RNA sequencing (RNA-Seq) to evaluate the transcriptional progression of in vitro-differentiated neural cells (over a timecourse of 0, 35, 70, 105 and 140 days), and compared this with donor-identical temporal lobe tissue. We observed in vitro progression towards the reference brain tissue, and the following three results support this conclusion: (i) there was a significant increasing monotonic correlation between the days of our timecourse and the number of actively transcribed protein-coding genes and long intergenic non-coding RNAs (lincRNAs) (P vitro to brain-tissue differences (P vitro neural development and physiological progression occurring predominantly by transcriptional activation of downregulated genes rather than deactivation of upregulated genes. PMID:23666530

  1. Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

    Science.gov (United States)

    Singh-Moon, Rajinder P.; Roblyer, Darren M.; Bigio, Irving J.; Joshi, Shailendra

    2014-09-01

    We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

  2. Tissue tears in the white matter after lateral fluid percussion brain injury in the rat: relevance to human brain injury.

    Science.gov (United States)

    Graham, D I; Raghupathi, R; Saatman, K E; Meaney, D; McIntosh, T K

    2000-02-01

    A characteristic feature of severe diffuse axonal injury in man is radiological evidence of the "shearing injury triad" represented by lesions, sometimes haemorrhagic, in the corpus callosum, deep white matter and the rostral brain stem. With the exception of studies carried out on the non-human primate, such lesions have not been replicated to date in the multiple and diverse rodent laboratory models of traumatic brain injury. The present report describes tissue tears in the white matter, particularly in the fimbria of Sprague-Dawley rats killed 12, 24, and 48 h and 7 days after lateral fluid percussion brain injury of moderate severity (2.1-2.4 atm). The lesions were most easily seen at 24 h when they appeared as foci of tissue rarefaction in which there were a few polymorphonuclear leucocytes. At the margins of these lesions, large amounts of accumulated amyloid precursor protein (APP) were found in axonal swellings and bulbs. By 1 week post-injury, there was macrophage infiltration with marked astrocytosis and early scar formation. This lesion is considered to be due to severe deformation of white matter and this is the first time that it has been identified reproducibly in a rodent model of head injury under controlled conditions.

  3. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  4. Sequential process in brain-derived neurotrophic factor-induced functional periodontal tissue regeneration.

    Science.gov (United States)

    Konishi, Akihiro; Takeda, Katsuhiro; Fujita, Tsuyoshi; Kajiya, Mikihito; Matsuda, Shinji; Kittaka, Mizuho; Shiba, Hideki; Kurihara, Hidemi

    2016-04-01

    We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin αVβ3, and integrin α2β1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration.

  5. The Brain.

    Science.gov (United States)

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  6. A new microcontroller-based human brain hypothermia system.

    Science.gov (United States)

    Kapidere, Metin; Ahiska, Raşit; Güler, Inan

    2005-10-01

    Many studies show that artificial hypothermia of brain in conditions of anesthesia with the rectal temperature lowered down to 33 degrees C produces pronounced prophylactic effect protecting the brain from anoxia. Out of the methods employed now in clinical practice for reducing the oxygen consumption by the cerebral tissue, the most efficacious is craniocerebral hypothermia (CCH). It is finding even more extensive application in cardiovascular surgery, neurosurgery, neurorenimatology and many other fields of medical practice. In this study, a microcontroller-based designed human brain hypothermia system (HBHS) is designed and constructed. The system is intended for cooling and heating the brain. HBHS consists of a thermoelectric hypothermic helmet, a control and a power unit. Helmet temperature is controlled by 8-bit PIC16F877 microcontroller which is programmed using MPLAB editor. Temperature is converted to 10-bit digital and is controlled automatically by the preset values which have been already entered in the microcontroller. Calibration is controlled and the working range is tested. Temperature of helmet is controlled between -5 and +46 degrees C by microcontroller, with the accuracy of +/-0.5 degrees C.

  7. Fusion analysis of first episode depression: Where brain shape deformations meet local composition of tissue

    Directory of Open Access Journals (Sweden)

    Mahdi Ramezani

    2015-01-01

    Full Text Available Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder. We use structural Magnetic Resonance Imaging (MRI data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create population gray matter (GM and white matter (WM tissue average templates using DARTEL groupwise registration. We obtained GM and WM tissue maps in the template space, along with the deformation fields required to co-register the DARTEL template and the GM and WM maps in the population. These three features, reflecting tissue composition and shape of the brain, were used within a joint independent-components analysis (jICA to extract spatially independent joint sources and their corresponding modulation profiles. Coefficients of the modulation profiles were used to capture differences between depressed and non-depressed groups. The combination of hippocampal shape deformations and local composition of tissue (but neither shape nor local composition of tissue alone was shown to discriminate reliably between individuals in a first episode of depression and healthy controls, suggesting that brain structural differences between depressed and non-depressed individuals do not simply reflect chronicity of the disorder but are there from the very outset.

  8. Fusion analysis of first episode depression: where brain shape deformations meet local composition of tissue.

    Science.gov (United States)

    Ramezani, Mahdi; Abolmaesumi, Purang; Tahmasebi, Amir; Bosma, Rachael; Tong, Ryan; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid

    2015-01-01

    Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create population gray matter (GM) and white matter (WM) tissue average templates using DARTEL groupwise registration. We obtained GM and WM tissue maps in the template space, along with the deformation fields required to co-register the DARTEL template and the GM and WM maps in the population. These three features, reflecting tissue composition and shape of the brain, were used within a joint independent-components analysis (jICA) to extract spatially independent joint sources and their corresponding modulation profiles. Coefficients of the modulation profiles were used to capture differences between depressed and non-depressed groups. The combination of hippocampal shape deformations and local composition of tissue (but neither shape nor local composition of tissue alone) was shown to discriminate reliably between individuals in a first episode of depression and healthy controls, suggesting that brain structural differences between depressed and non-depressed individuals do not simply reflect chronicity of the disorder but are there from the very outset.

  9. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery.

    Science.gov (United States)

    Han, Eun Young; Zhang, Xin; Yan, Yulong; Sharma, Sunil; Penagaricano, Jose; Moros, Eduardo; Corry, Peter

    2012-01-01

    At the University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  10. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    Science.gov (United States)

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  11. The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

    Directory of Open Access Journals (Sweden)

    Antony Harding

    2009-01-01

    Full Text Available New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders.

  12. Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

    DEFF Research Database (Denmark)

    Lof, A.; Lam, Henrik Rye; Gullstrand, E.

    1999-01-01

    spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure....... Two hours after the end of exposure the n-decane concentration decreased to about 25% in blood and 50% in brain. A similar pattern of elimination was also observed for n-nonane, n-undecane and total white spirit in blood and brain. In fat tissue the concentrations of n-nonane, n-decane, n......-undecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After the 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-undecane, and total white spirit decreased very slowly compared with the rate of decrease...

  13. Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment

    Directory of Open Access Journals (Sweden)

    Sun H

    2016-08-01

    Full Text Available Hongtao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2 in the course of mild hypothermia treatment (MHT for treating severe traumatic brain injury (sTBI. Methods: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP, jugular venous oxygen saturation (SjvO2, and cerebral perfusion pressure (CPP were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. Keywords: severe traumatic brain injury, hypothermia, brain tissue partial pressure of oxygen, therapy

  14. Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

    Science.gov (United States)

    Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

    2015-02-01

    Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

  15. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

    Directory of Open Access Journals (Sweden)

    Kenne Ellinor

    2012-01-01

    Full Text Available Abstract Background Brain edema as a result of secondary injury following traumatic brain injury (TBI is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI. Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice.

  16. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  17. Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre.

    Science.gov (United States)

    Harper, Clive; Dixon, Gavin; Sheedy, Donna; Garrick, Therese

    2003-09-01

    Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily. Excessive drinking can lead to impairment of cognitive function and structural brain changes--some permanent, some reversible. Patterns of damage appear to relate to lifetime alcohol consumption but, more importantly, to associated medical complications. The most significant of these is the alcohol-related vitamin deficient state, the Wernicke-Korsakoff syndrome (WKS), which is caused by thiamin deficiency but is seen most commonly in alcoholics. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses has provided data that gives clues to the most vulnerable regions and cells in the brain. Brain shrinkage is largely accounted for by loss of white matter. Some of this damage appears to be reversible. Alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus and cerebellum. No change is found in basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of these regions which are normal in uncomplicated alcoholics are damaged in those with the WKS. Dendritic and synaptic changes have been documented in alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits, which precede more severe structural neuronal changes. A resource to provide human brain tissues for these types of studies has been developed at the University of Sydney--the New South Wales Tissue Resource Centre. The aim of this facility is to provide research groups throughout the world with fresh and/or frozen tissues from well-characterized cases of alcohol-related brain damage and matched

  18. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies

    OpenAIRE

    Boellaard, Ronald; Hinz, Rainer; Adriaan A. Lammertsma; Schuitemaker, Alie; Tomasi, Giampaolo; Turkheimer, Federico E.; van Berckel, Bart NM; Yaqub, Maqsood

    2012-01-01

    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[(11)C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were ana...

  19. Increased brain tissue sodium concentration in Huntington's Disease - a sodium imaging study at 4 T.

    Science.gov (United States)

    Reetz, Kathrin; Romanzetti, Sandro; Dogan, Imis; Saß, Christian; Werner, Cornelius J; Schiefer, Johannes; Schulz, Jörg B; Shah, N Jon

    2012-10-15

    The neuropathological hallmark of the autosomal dominantly inherited, neurodegenerative disorder Huntington's disease is progressive striatal loss starting several years prior to symptom manifestation. Magnetic resonance (MR) imaging has been widely used to detect altered structure in premanifest and early Huntington's disease. Given that neurodegeneration is likely preceded by substantial neuronal dysfunction, we used in vivo sodium MR imaging, which has been shown to be sensitive to cell death and viability, to investigate cellular and metabolic integrity of Huntington's disease brain tissue. We studied a total of thirteen healthy controls and thirteen Huntington's disease gene carriers (11 manifest and 2 premanifest). The manifest Huntington's disease group was subdivided into stages 1 and 2 according to their Total Functional Capacity scores. Clinical total motor and cognitive scores, as well as calibrated sodium and T1-weighted MR images were obtained with a 4 T Siemens MR scanner. Sodium images were acquired by means of a constant time imaging technique with an ultra-short "echo time". T1-weighted MR images were further analysed with voxel-based morphometry. The absolute total sodium concentration and grey matter values were measured in several Huntington's disease-specific and also non-specific areas. Statistical analysis of variance and Pearson correlation were applied. In Huntington's disease subjects, we found an increase of total sodium concentration of the entire brain compared to controls. Increased total sodium concentration values were found in structurally affected, but also in some non-affected, regions. The highest total sodium concentration values were found in the bilateral caudate, which was associated with caudate grey matter atrophy and CAG repeat length. In all Huntington's disease subjects we further found a profound increase of total sodium concentration in the putamen, pallidum, thalamus, hippocampus, insula, precuneus and occipital

  20. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  1. Development and calculation of an energy dependent normal brain tissue neutron RBE for evaluating neutron fields for BNCT.

    Science.gov (United States)

    Woollard, J E; Blue, T E; Gupta, N; Gahbauer, R A

    2001-06-01

    In Boron Neutron Capture Therapy (BNCT) of malignant brain tumors, the energy dependence of a clinically relevant Relative Biological Effectiveness (RBE) for epithermal neutrons, RBE(En), is important in neutron field design. In the first half of this paper, we present the development of an expression for the energy dependent normal-tissue RBE, RBE(En). We then calculate a reasonable estimate for RBE(En) for adult brain tissue. In the second half of the paper, two separate RBE expressions are developed, one for the RBE of the neutrons that interact in tissue via the 14N(n,p)14C reaction, denoted RBE(N), and one for the RBE of the neutrons which interact in tissue via the 1H(n,n')1H reaction, denoted RBE(H). The absorbed-dose-averaged values of these expressions are calculated for the neutron flux spectrum in phantom for the Brookhaven Medical Research Reactor (BMRR) epithermal neutron beam. The calculated values, [RBE(norm)N] = 3.4 and [RBE(norm)H] = 3.2, are within 6% of being equal, and support the use of equal values for RBEN and RBE(H) by researchers at Brookhaven National Laboratory (BNL). Finally, values of [RBE(norm)N] and [RBE(norm)H], along with the absorbed-dose-averaged RBE for brain, [RBE(norm)b], were calculated as a function of depth along the centerline of an ellipsoidal head phantom using flux spectra calculated for our Accelerator-Based Neutron Source (ABNS). These values remained essentially constant with depth, supporting the use of constant values for RBE, as is done at BNL.

  2. Brain death and tissue and organ transplantation: the understanding of medical students.

    Science.gov (United States)

    dos Reis, Flávio Pola; Gomes, Bruno Henrique Pinto; Pimenta, Lucas Lopes; Etzel, Arnaldo

    2013-01-01

    To evaluate the level of knowledge of medical students about transplantation and brain death. An anonymous self-administered questionnaire answered by medical students from the first through the sixth year that was based on information from the Associação Brasileira de Transplante de Órgãos e Tecidos, the Registro Brasileiro de Transplantes and the resolution that defines the criteria for brain death. Of the 677 medical students asked, 310 (45.8%) agreed to answer the questionnaire. In total, 22 (7.0%) subjects were excluded. Of the students who participated, 41.3% reported having already attended a class on organ transplantation and 33% on brain death; 9.7% felt able to diagnose brain death (ptransplanted solid organ in Brazil. The level of knowledge of medical students at this institution regarding brain death and transplantation is limited, which may be the result of an inadequate approach during medical school.

  3. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  4. Identifying signature Zernike modes for efficient light delivery through brain tissue

    CERN Document Server

    Sane, Sharmila; Lee, Woei Ming; Stricker, Christian; Bachor, Hans; Daria, Vincent

    2015-01-01

    Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions of the wavefront of the incoming light which broadens the focus, thereby reducing the intensity and resolution especially in techniques requiring focal illumination. Adaptive wavefront correction has been demonstrated to compensate for these distortions. However, in many situations iterative derivation of the corrective wavefront introduces time constraints that limit its usefulness when used to probe living cells. Here we demonstrate a direct and fast technique by working with a small set of Zernike modes and demonstrate that corrections derived a priori can lead to significant improvement of the focus. We verify this idea by the electrical response of whole-cell patched neurons following t...

  5. Changes of amino acid gradients in brain tissues induced by microwave irradiation and other means

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, C.F.; Parsons, J.E.; Oh, C.C.; Wasterlain, C.G.; Baldwin, R.A. (Neurochem. Labs, V.A. Med. Ctr. Sepulveda, CA (USA))

    1989-09-01

    Focused microwave irradiation to the head (FMI) has been used extensively by neurochemists for rapid inactivation of enzymatic activity in brain tissues and the preservation, for in vitro analysis, of in vivo substrate concentrations. Periodically the suitability of this technique for regional studies has been questioned. Evidence has now been obtained, on the basis of altered concentration gradients for GABA and taurine from the Substantia Nigra (SN) to an Adjacent Dorsal Area (ADJ), that FMI not only inactivates enzymes, but also facilitates rapid diffusion of small molecules from areas of high concentrations to adjacent areas of lower concentration. To a lesser extent, the implantation of plastic injection cannulas also decreased these concentration gradients. These results offer clear evidence that FMI is ill suited and unreliable for studies designed to map and compare the in vivo regional concentrations of diffusible organic molecules (such as amino acids) in brain tissues. Any invasive technique that compromises membrane barriers is likely to produce smaller similar effects.

  6. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    Science.gov (United States)

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  7. Identification, tissue distribution and evaluation of brain neuropeptide Y gene expression in the Brazilian flounder Paralichthys orbignyanus

    Indian Academy of Sciences (India)

    Vinicius F Campos; Tiago Collares; João C Deschamps; Fabiana K Seixas; Odir A Dellagostin; Carlos Frederico C Lanes; Juliana Sandrini; Luis Fernando Marins; Marcelo Okamoto; Luís A Sampaio; Ricardo B Robaldo

    2010-09-01

    Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in vertebrates, mammals and fish. However, the present knowledge about feeding behaviour in fish is still limited and based on studies in a few species. The Brazilian flounder Paralichthys orbignyanus is being considered for aquaculture, and it is important to understand the mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from Brazilian flounder brain. NPY expression was detected in all the peripheral tissues analysed. No significant differences were observed in brain NPY gene expression over 24 h after food intake at a temperature of 15 ± 3°C. No correlation was observed among plasma glucose, total protein, cholesterol, triglycerides and NPY expression levels during this 24 h period. On the other hand, mRNA levels were increased after two weeks of fasting at elevated temperatures. Our results suggest that NPY mRNA levels in Brazilian flounder are affected by temperature.

  8. Acupuncture activates signal transduction pathways related to brain-tissue restoration after ischemic injury.

    Science.gov (United States)

    Tian, Haomei; Zhang, Hong; Zhu, Junbao; Zhang, Juan; Cai, Hening; Zhang, Yuchen; Chen, Chutao

    2012-08-25

    A middle cerebral artery occlusion-model was established in rats using the improved thread embolism method. Rats were treated with acupuncture at either Dazhui (DU14), Renzhong (DU26), Baihui (DU20), or a non-meridian point. Detection with protein-chip technology showed that the level of protein phosphorylation in both groups was upregulated or downregulated depending on the signaling pathway compared with the model group that did not receive acupuncture. Analysis of proteins showing downregulated phosphorylation revealed that five signaling pathways were activated in the acupuncture-treatment group, while only two were activated in the acupuncture- control group. In contrast, analysis of proteins showing upregulated phosphorylation revealed only one pathway was activated in the acupuncture-treatment group, whereas four pathways were activated in the acupuncture-control group. Furthermore, the number of activated proteins in the acupuncture-treatment group was not only higher than the acupuncture-control group, but unlike the acupuncture-control group, the majority of activated proteins were key proteins in the signaling pathways. Our findings indicate that acupuncture at specific points can activate multiple signaling pathways to promote the restoration of brain tissue following ischemic injury, and that this is based on a combination of effects resulting from multiple pathways, targets, and means.

  9. Concentrations of Nitric Oxide in Rat Brain Tissues after Diffuse Brain Injury and Neuroprotection by the Selective Inducible Nitric Oxide Synthase Inhibitor Aminoguanidine

    Institute of Scientific and Technical Information of China (English)

    Yi-bao Wang; Shao-wu Ou; Guang-yu Li; Yun-hui Liu

    2005-01-01

    @@ To investigate the effects of nitric oxide (NO) and the selective inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (AG) on trauma, we explored the concentrations of nitric oxide in rat brain tissues at different time stamps after diffuse brain injury (DBI) with or without AG treatment.

  10. Focussed Ion Beam Milling and Scanning Electron Microscopy of Brain Tissue

    OpenAIRE

    Knott, Graham; Rosset, Stéphanie; Cantoni, Marco

    2011-01-01

    This protocol describes how biological samples, like brain tissue, can be imaged in three dimensions using the focussed ion beam/scanning electron microscope (FIB/SEM). The samples are fixed with aldehydes, heavy metal stained using osmium tetroxide and uranyl acetate. They are then dehydrated with alcohol and infiltrated with resin, which is then hardened. Using a light microscope and ultramicrotome with glass knives, a small block containing the region interest close to the surface is made....

  11. Neural mass model-based tracking of anesthetic brain states

    NARCIS (Netherlands)

    Kuhlmann, Levin; Freestone, Dean R.; Manton, Jonathan H.; Heyse, Bjorn; Vereecke, Hugo E. M.; Lipping, Tarmo; Struys, Michel M. R. F.; Liley, David T. J.

    2016-01-01

    Neural mass model-based tracking of brain states from electroencephalographic signals holds the promise of simultaneously tracking brain states while inferring underlying physiological changes in various neuroscientific and clinical applications. Here, neural mass model-based tracking of brain state

  12. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  13. Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

    Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

  14. Mechanical Characterization of Brain Tissue in Compression at Dynamic Strain Rates

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.01.022

    2013-01-01

    Traumatic brain injury (TBI) occurs when local mechanical load exceeds certain tolerance levels for brain tissue. Extensive research has been done previously for brain matter experiencing compression at quasistatic loading; however, limited data is available to model TBI under dynamic impact conditions. In this research, an experimental setup was developed to perform unconfined compression tests and stress relaxation tests at strain rates < 90/s. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the compressive nominal stress at 30% strain was 8.83 +/- 1.94, 12.8 +/- 3.10 and 16.0 +/- 1.41 kPa (mean +/- SD) at strain rates of 30, 60 and 90/s, respectively. Relaxation tests were also conducted at 10%-50% strain with the average rise time of 10 ms, which can be used to derive time dependent parameters. Numerical simulations were performed using one-term Ogden model with initial shear modulus mu_0 = 6.06 +/- 1.44, 9.44 +/-...

  15. Protein analysis through Western blot of cells excised individually from human brain and muscle tissue.

    Science.gov (United States)

    Koob, A O; Bruns, L; Prassler, C; Masliah, E; Klopstock, T; Bender, A

    2012-06-15

    Comparing protein levels from single cells in tissue has not been achieved through Western blot. Laser capture microdissection allows for the ability to excise single cells from sectioned tissue and compile an aggregate of cells in lysis buffer. In this study we analyzed proteins from cells excised individually from brain and muscle tissue through Western blot. After we excised individual neurons from the substantia nigra of the brain, the accumulated surface area of the individual cells was 120,000, 24,000, 360,000, 480,000, 600,000 μm2. We used an optimized Western blot protocol to probe for tyrosine hydroxylase in this cell pool. We also took 360,000 μm2 of astrocytes (1700 cells) and analyzed the specificity of the method. In muscle we were able to analyze the proteins of the five complexes of the electron transport chain through Western blot from 200 human cells. With this method, we demonstrate the ability to compare cell-specific protein levels in the brain and muscle and describe for the first time how to visualize proteins through Western blot from cells captured individually. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Optical vortex beam transmission with different OAM in scattering beads and brain tissue media

    Science.gov (United States)

    Wang, W. B.; Shi, Lingyan; Lindwasser, Lukas; Marque, Paulo; Lavery, M. P. J.; Alfano, R. R.

    2016-03-01

    Light transmission of Laguerre Gaussian (LG) vortex beams with different orbital angular momentum (OAM) values (L) in scattering beads and mouse brain tissue media were experimentally investigated for the first time in comparison with Gaussian (G) beams. The LG beams with different OAM were generated using a spatial light modulator (SLM) in reflection mode. The scattering beads media consist of various sizes and concentrations of latex beads in water solutions. The transmissions of LG and G beams through scattering beads and brain tissue media were measured with different ratios of sample thicknesses (z) to scattering mean free path (ls) of the turbid media, z/ls. The results indicate that within the ballistic region where z/ls is small, the LG and G beams show no significant difference, while in the diffusive region where z/ls is higher, the vortex beams show higher transmission than G beams. In the diffusive region, the LG beams with higher L values show higher transmission than the beams with lower L values due to the eigen channels in the media. The transition points from the ballistic to diffusive regions for different scattering beads and brain tissue media were studied.

  17. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  18. [Influence of n-hexane on vascular endothelial active substances in brain tissue in mice].

    Science.gov (United States)

    Lin, L; Zhang, Z Q; Zhang, C Z

    2017-01-20

    Objective: To investigate the influence of n-hexane on vascular endothelial active substances in brain tissue in mice and its significance. Methods: A total of 48 healthy Kunming mice were randomly divided into high-dose exposure group, middle-dose exposure group, low-dose exposure group, and control group, with 12 mice in each group. All groups except the control group were exposed to n-hexane via static inhalation (0.035 g/L, 0.018 g/L, and 0.009 g/L for the high-, middle-, and low-dose exposure groups, respectively) 4 hours a day for 21 days. the mice in the control groups were not exposed to n-hexane. After the exposure, the lev-els of endothelin-1 (ET-1) , nitric oxide (NO) , and angiotensin II (Ang II) in brain tissue were measured in all groups. Results: There were significant differences in the levels of ET-1, NO, and Ang II between the three ex-posure groups and the control group (PHexane can affect the vascular endothe-lial active substances in brain tissue in mice, and the changes and imbalance in vascular endothelial active sub-stances may be one of the reasons for central nervous system impairment caused by n-hexane.

  19. Preliminary observation of genes specifically expressed in brain tissues during stroke-like episodes in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Xian-mei; ZHAO Bin; ZHU Shan-jun; ZHU Zhi-ming; ZHANG Qian; HUI Ru-tai

    2001-01-01

    Objective: To observe the difference of gene expressions of brain tissues during apoplectic episodes and those of normal brain in Wistar rats in order to study the pathological mechanism of apoplexy. Methods: A rat model of hypertension was established with the administration of cold stimulus and high salt intake as the environmental risk factors.Apoplexy occurred in the rats because of hypertension. Suppression subtractive hybridization(SSH) was used to identify and analyze the differential genes specifically expressed in cerebral tissues of stoke group and control rats. Results: A total of 226 genes out of the 228 were usable and analyzed. The average length of the 226 genes was (286.6±120.3) bp with a range from 50 bp to 619 bp. And 126 clones out of the 226 showed a sequence with significant identity to the known genes; 78 clones demonstrated homogenous sequences to the existing ESTs ofdbEST, but no one of the 78 showed sequence with identity to that of known genes; and remaining 22 were novel transrcipts exhibiting no similarity to any known sequences. All the clones which were highly homogenous to the known genes were categorized on the basis of their function. It was found that 26.5% of the mitochodrial genes in brain tissues underwent changes after apoplexy and the changes showed a twofold relationship of cause and effect. Conclusion: Environmental factors are able to induce changes of gene expression, which may increase the sensitivity to apoplectic stroke.

  20. THE STATE OF THE WATER IN BRAIN TISSUE IN PRESENCE OF TS-100 NANOPARTICLES

    Directory of Open Access Journals (Sweden)

    T. V.

    2015-12-01

    Full Text Available By the method of low-temperature 1Н NMR spectroscopy the structure of the hydrate layers of water associated with brain cells, the changes of these parameters during necrotic lesions (stroke and in the presence of trifluoroacetic acid, which allows differentiating intracellular water clusters according to their ability to dissolve the acid, were studied. Also the impact of silica TS-100 nanoparticles on the state of water in brain tissue, namely on the water binding parameters in the air and in the presence of a weakly polar solvent was considered. The distributions by the radii and change of Gibbs free energy for clusters of strongly bound interfacial water were obtained. It was shown that the hydration properties of the native brain tissue differ from the hydration properties of necrotic damaged tissue by the structure of weakly bound water clusters. In intact tissue all the water is associated and is a part of clusters and domains, most of which have a radii R = 2 and 20 nm. The media with chloroform stabilizes water polyassociates with the radius up to R = 100 nm and trifluoroacetic acid stabilizes water polyassociates with radii R = 7–20 nm. It was found that the partial dehydration of the investigated tissue samples is accompanied by decreasing of weakly bound water amount and some increasing of strongly bound water that indicates a change of molecular interactions between the components of cells-nanoparticles composite system. The ischemic necrosis area presence leads to a decrease of water binding due to the average size water polyassociates increasing. This effect is observed both in air and in a weakly polar organic solvent medium (deuterochloroform.

  1. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    Science.gov (United States)

    Jugé, Lauriane; Pong, Alice C; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P hydrocephalus development.

  2. A comparison of hyperelastic constitutive models applicable to brain and fat tissues.

    Science.gov (United States)

    Mihai, L Angela; Chin, LiKang; Janmey, Paul A; Goriely, Alain

    2015-09-06

    In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney-Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations.

  3. Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

    Science.gov (United States)

    Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

    2016-03-01

    Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

  4. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We...... report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  5. Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue.

    Science.gov (United States)

    Godridge, H; Reynolds, G P; Czudek, C; Calcutt, N A; Benton, M

    1987-01-01

    Brain tissue taken at necropsy from five cases of Down's syndrome and six controls was analysed for changes in neurotransmitter markers. Concentrations of noradrenaline (NA), dopamine (DA) and its major metabolite homovanillic acid (HVA), 5-hydroxytryptamine (5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by means of HPLC, whilst choline acetyltransferase (ChAT) was measured by a radiochemical technique. Significant reductions in NA, 5HT and ChAT were found in most cortical and subcortical regions of the Down's syndrome tissue investigated. The neuropathological lesions were assessed using a fluorescent stain for neuritic plaques and neurofibrillary tangles. These were present to varying extents in every Down's syndrome case except the youngest but were not found in control tissue of comparable age. The results indicate profound transmitter deficits and neuropathological abnormalities in adult patients with Down's syndrome, which closely resemble those of Alzheimer's disease. PMID:2440994

  6. Evaluation of three-dimensional anisotropic head model for mapping realistic electromagnetic fields of brain tissues

    OpenAIRE

    Woo Chul Jeong; Hun Wi; Saurav Z. K. Sajib; Tong In Oh; Hyung Joong Kim; Oh In Kwon; Eung Je Woo

    2015-01-01

    Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR)-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understan...

  7. Supervised novelty detection in brain tissue classification with an application to white matter hyperintensities

    Science.gov (United States)

    Kuijf, Hugo J.; Moeskops, Pim; de Vos, Bob D.; Bouvy, Willem H.; de Bresser, Jeroen; Biessels, Geert Jan; Viergever, Max A.; Vincken, Koen L.

    2016-03-01

    Novelty detection is concerned with identifying test data that differs from the training data of a classifier. In the case of brain MR images, pathology or imaging artefacts are examples of untrained data. In this proof-of-principle study, we measure the behaviour of a classifier during the classification of trained labels (i.e. normal brain tissue). Next, we devise a measure that distinguishes normal classifier behaviour from abnormal behavior that occurs in the case of a novelty. This will be evaluated by training a kNN classifier on normal brain tissue, applying it to images with an untrained pathology (white matter hyperintensities (WMH)), and determine if our measure is able to identify abnormal classifier behaviour at WMH locations. For our kNN classifier, behaviour is modelled as the mean, median, or q1 distance to the k nearest points. Healthy tissue was trained on 15 images; classifier behaviour was trained/tested on 5 images with leave-one-out cross-validation. For each trained class, we measure the distribution of mean/median/q1 distances to the k nearest point. Next, for each test voxel, we compute its Z-score with respect to the measured distribution of its predicted label. We consider a Z-score >=4 abnormal behaviour of the classifier, having a probability due to chance of 0.000032. Our measure identified >90% of WMH volume and also highlighted other non-trained findings. The latter being predominantly vessels, cerebral falx, brain mask errors, choroid plexus. This measure is generalizable to other classifiers and might help in detecting unexpected findings or novelties by measuring classifier behaviour.

  8. Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

    Science.gov (United States)

    Takahashi, Hironobu; Okano, Teruo

    2015-11-18

    In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

    Directory of Open Access Journals (Sweden)

    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

  10. New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains.

    Science.gov (United States)

    Miyata, Seiji

    2015-01-01

    The blood-brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both of

  11. PLA-based foams: tissue engineering

    OpenAIRE

    Velasco Perero, José Ignacio; Antunes, Marcelo de Sousa Pais

    2015-01-01

    Biodegradable porous scaffolds with or without bioactive molecules prepared by clean techniques attract an enormous interest for tissue engineering applications. Scaffolds work as structural support for both cell implantation and growth, favoring the regeneration or formation of new tissue. Scaffold requisites for tissue engineering applications include a proper material selection, which has to be biocompatible and biodegradable and with a good balance of mechanical properties, as...

  12. A Novel Statistical Approach for Brain MR Images Segmentation Based on Relaxation Times

    Directory of Open Access Journals (Sweden)

    Fabio Baselice

    2015-01-01

    Full Text Available Brain tissue segmentation in Magnetic Resonance Imaging is useful for a wide range of applications. Classical approaches exploit the gray levels image and implement criteria for differentiating regions. Within this paper a novel approach for brain tissue joint segmentation and classification is presented. Starting from the estimation of proton density and relaxation times, we propose a novel method for identifying the optimal decision regions. The approach exploits the statistical distribution of the involved signals in the complex domain. The technique, compared to classical threshold based ones, is able to globally improve the classification rate. The effectiveness of the approach is evaluated on both simulated and real datasets.

  13. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M;

    1983-01-01

    ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion......In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...... the infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively...

  14. Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue.

    Science.gov (United States)

    Häke, Ines; Schönenberger, Silvia; Neumann, Jens; Franke, Katrin; Paulsen-Merker, Katrin; Reymann, Klaus; Ismail, Ghazally; Bin Din, Laily; Said, Ikram M; Latiff, A; Wessjohann, Ludger; Zipp, Frauke; Ullrich, Oliver

    2009-01-03

    Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 microg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.

  15. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    Science.gov (United States)

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P brain (P brain, liver, and kidney (all P brain (all P brain (P drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  16. Touch-based Brain Computer Interfaces: State of the art

    NARCIS (Netherlands)

    Erp, J.B.F. van; Brouwer, A.M.

    2014-01-01

    Brain Computer Interfaces (BCIs) rely on the user's brain activity to control equipment or computer devices. Many BCIs are based on imagined movement (called active BCIs) or the fact that brain patterns differ in reaction to relevant or attended stimuli in comparison to irrelevant or unattended

  17. Brain-Based Education: Its Pedagogical Implications and Research Relevance

    Science.gov (United States)

    Laxman, Kumar; Chin, Yap Kueh

    2010-01-01

    The brain, being the organ of learning, must be understood if classrooms are to be places of meaningful learning. Understanding the brain has the potential to alter the foundation of education, transform traditional classrooms to interactive learning environments and promote better instructional approaches amongst teachers. Brain-based education…

  18. Touch-based Brain Computer Interfaces: State of the art

    NARCIS (Netherlands)

    Erp, J.B.F. van; Brouwer, A.M.

    2014-01-01

    Brain Computer Interfaces (BCIs) rely on the user's brain activity to control equipment or computer devices. Many BCIs are based on imagined movement (called active BCIs) or the fact that brain patterns differ in reaction to relevant or attended stimuli in comparison to irrelevant or unattended stim

  19. Scattering of Sculpted Light in Intact Brain Tissue, with implications for Optogenetics

    Science.gov (United States)

    Favre-Bulle, Itia A.; Preece, Daryl; Nieminen, Timo A.; Heap, Lucy A.; Scott, Ethan K.; Rubinsztein-Dunlop, Halina

    2015-06-01

    Optogenetics uses light to control and observe the activity of neurons, often using a focused laser beam. As brain tissue is a scattering medium, beams are distorted and spread with propagation through neural tissue, and the beam’s degradation has important implications in optogenetic experiments. To address this, we present an analysis of scattering and loss of intensity of focused laser beams at different depths within the brains of zebrafish larvae. Our experimental set-up uses a 488 nm laser and a spatial light modulator to focus a diffraction-limited spot of light within the brain. We use a combination of experimental measurements of back-scattered light in live larvae and computational modelling of the scattering to determine the spatial distribution of light. Modelling is performed using the Monte Carlo method, supported by generalised Lorenz-Mie theory in the single-scattering approximation. Scattering in areas rich in cell bodies is compared to that of regions of neuropil to identify the distinct and dramatic contributions that cell nuclei make to scattering. We demonstrate the feasibility of illuminating individual neurons, even in nucleus-rich areas, at depths beyond 100 μm using a spatial light modulator in combination with a standard laser and microscope optics.

  20. Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography.

    Directory of Open Access Journals (Sweden)

    Daniel F Hughes

    Full Text Available Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we

  1. Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography.

    Science.gov (United States)

    Hughes, Daniel F; Walker, Ellen M; Gignac, Paul M; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S; Greenbaum, Eli; Khan, Arshad M

    2016-01-01

    Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated

  2. Effects of formalin fixation, paraffin embedding, and time of storage on DNA preservation in brain tissue: a BrainNet Europe study.

    Science.gov (United States)

    Ferrer, Isidre; Armstrong, Judith; Capellari, Sabina; Parchi, Piero; Arzberger, Thomas; Bell, Jeanne; Budka, Herbert; Ströbel, Thomas; Giaccone, Giorgio; Rossi, Giacomina; Bogdanovic, Nenad; Fakai, Peter; Schmitt, Andrea; Riederers, Peter; Al-Sarraj, Safa; Ravid, Rivka; Kretzschmar, Hans

    2007-07-01

    There is a large amount of tissue stored in brain collections and brain banks, but little is known about whether formalin-fixed tissues and paraffin blocks stored for years in brain banks are suitable for the retrospective genetic studies. The study was carried out in order to: (i) compare DNA preservation in frozen, formalin-fixed and paraffin-embedded tissues stored for different periods; (ii) study point mutations and triplet expansions in frozen, formalin-fixed and paraffin-embedded material stored for variable periods, and using different fixative solutions; (iii) compare different methods to optimize DNA extraction and DNA amplification from suboptimally preserved brain tissue. DNA preservation is suitable for genetic studies in samples stored at -80 degrees C for several years. Formalin-fixed, paraffin-embedded tissue was inferior to frozen tissue, but did yield adequate results in many cases depending on the type of fixative solution and time of fixation before embedding. Prolonged fixation in formalin rarely yielded useful DNA. Similar results were obtained in samples from prion diseases. The best results were obtained by using the Qiagen kits (QIAmp DNA Micro) in frozen material, paraffin blocks and formalin-fixed tissue. Genomiphi and TaKaRa Ex Taq methods were also assayed in paraffin blocks and in formalin-fixed samples with limited success.

  3. A Novel Albumin-Based Tissue Scaffold for Autogenic Tissue Engineering Applications

    Science.gov (United States)

    Li, Pei-Shan; -Liang Lee, I.; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin

    2014-07-01

    Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes.

  4. A white matter lesion-filling approach to improve brain tissue volume measurements

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2014-01-01

    Full Text Available Multiple sclerosis white matter (WM lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  5. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  6. An empirical approach to estimate near-infra-red photon propagation and optically induced drug release in brain tissues

    Science.gov (United States)

    Prabhu Verleker, Akshay; Fang, Qianqian; Choi, Mi-Ran; Clare, Susan; Stantz, Keith M.

    2015-03-01

    The purpose of this study is to develop an alternate empirical approach to estimate near-infra-red (NIR) photon propagation and quantify optically induced drug release in brain metastasis, without relying on computationally expensive Monte Carlo techniques (gold standard). Targeted drug delivery with optically induced drug release is a noninvasive means to treat cancers and metastasis. This study is part of a larger project to treat brain metastasis by delivering lapatinib-drug-nanocomplexes and activating NIR-induced drug release. The empirical model was developed using a weighted approach to estimate photon scattering in tissues and calibrated using a GPU based 3D Monte Carlo. The empirical model was developed and tested against Monte Carlo in optical brain phantoms for pencil beams (width 1mm) and broad beams (width 10mm). The empirical algorithm was tested against the Monte Carlo for different albedos along with diffusion equation and in simulated brain phantoms resembling white-matter (μs'=8.25mm-1, μa=0.005mm-1) and gray-matter (μs'=2.45mm-1, μa=0.035mm-1) at wavelength 800nm. The goodness of fit between the two models was determined using coefficient of determination (R-squared analysis). Preliminary results show the Empirical algorithm matches Monte Carlo simulated fluence over a wide range of albedo (0.7 to 0.99), while the diffusion equation fails for lower albedo. The photon fluence generated by empirical code matched the Monte Carlo in homogeneous phantoms (R2=0.99). While GPU based Monte Carlo achieved 300X acceleration compared to earlier CPU based models, the empirical code is 700X faster than the Monte Carlo for a typical super-Gaussian laser beam.

  7. Detection of constitutive and inducible HSP70 proteins in formalin fixed human brain tissue.

    Science.gov (United States)

    Preusse-Prange, A; Modrow, J-H; Schwark, T; von Wurmb-Schwark, N

    2014-02-01

    The investigation of formalin fixed and paraffin embedded tissue is a routine method in forensic histology. Since these samples are usually stored for decades they provide a unique tissue bank for different scientific issues. In the past, numerous studies were conducted using different kinds of paraffin embedded tissues. However, it is well known that formalin affects macromolecules and thus might hamper reliable and reproducible molecular experiments. The aim of this study was to find out if the treatment with formalin has a negative effect on different protein detection methods and additionally to define the dimension of those possible deleterious effects. We incubated brain tissue samples in formalin for up to three months. After incubation, the samples were analyzed using immunohistochemistry (IHC) and Western blotting to specifically detect and quantify members of the HSP70 superfamily (heat shock proteins). Our study shows that the Western blot analysis of formalin fixed tissues does not allow a reliable detection of proteins at all, while a reproducible detection by IHC was still possible after one month of incubation.

  8. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. (Cleveland Clinic Foundation, OH (USA))

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

  9. Stages of restricted HIV-1 infection in astrocyte cultures derived from human fetal brain tissue.

    Science.gov (United States)

    Messam, C A; Major, E O

    2000-05-01

    The predominant cell types infected by HIV-1 in AIDS associated encephalopathy are cells of the macrophage/microglial lineage. There has been consistent evidence, however, that astrocytes also become infected although not at the same frequency or level of multiplication as microglial cells. HIV-1 antigens and/or nucleic acid have been identified in astrocytes in brain autopsy tissue from both adult and pediatric AIDS cases. In cell cultures, HIV-1 infection of astrocytes results in an initial productive but non-cytopathogenic infection that diminishes to a viral persistence or latent state. Understanding the nature of HIV-1 infection of astrocytes, which represents the largest population of cells in the brain, will contribute to the understanding of AIDS encephalopathy and the dementia that occurs in nearly one-quarter of all AIDS patients.

  10. A biphasic hyperelastic model for the analysis of fluid and mass transport in brain tissue.

    Science.gov (United States)

    García, José Jaime; Smith, Joshua H

    2009-02-01

    A biphasic hyperelastic finite element model is proposed for the description of the mechanical behavior of brain tissue. The model takes into account finite deformations through an Ogden-type hyperelastic compressible function and a hydraulic conductivity dependent on deformation. The biphasic equations, implemented here for spherical symmetry using an updated Lagrangian algorithm, yielded radial coordinates and fluid velocities that were used with the convective-diffusive equation in order to predict mass transport in the brain. Results of the model were equal to those of a closed-form solution under infinitesimal deformations, however, for a wide range of material parameters, the model predicted important increments in the infusion sphere, reductions of the fluid velocities, and changes in the species content distribution. In addition, high localized deformation and stresses were obtained at the infusion sphere. Differences with the infinitesimal solution may be mainly attributed to geometrical nonlinearities related to the increment of the infusion sphere and not to material nonlinearities.

  11. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI.

    Science.gov (United States)

    Scott, Julia A; Habas, Piotr A; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S; Corbett-Detig, James M; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2011-08-01

    In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. Published by Elsevier Ltd.

  12. Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

    Science.gov (United States)

    Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

    2014-03-01

    The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

  13. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  14. Assessment of Breast, Brain and Skin Pathological Tissue Using Full Field OCM

    Science.gov (United States)

    Dalimier, Eugénie; Assayag, Osnath; Harms, Fabrice; Boccara, A. Claude

    The aim of this chapter is to assess whether the images of the breast, brain, and skin tissue obtained by FFOCM contain sufficient detail to allow pathologists to make a diagnosis of cancer and other pathologies comparable to what was obtained by conventional histological techniques. More precisely, it is necessary to verify on FFOCM images if it is possible to differentiate a healthy area from a pathological area. The reader interested in other organs or in animal studies may find a large number of 2D or 3D images in the atlas [2].

  15. Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation.

    Science.gov (United States)

    Serulle, Yafell; Rusinek, Henry; Kirov, Ivan I; Milch, Hannah; Fieremans, Els; Baxter, Alexander B; McMenamy, John; Jain, Rajan; Wisoff, Jeffrey; Golomb, James; Gonen, Oded; George, Ajax E

    2014-10-01

    Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33% relative to HC characterized AD (P normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3% accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.

  16. Diffusion tensor imaging measures of white matter compared to myelin basic protein immunofluorescence in tissue cleared intact brains

    Directory of Open Access Journals (Sweden)

    Eric H. Chang

    2017-02-01

    Full Text Available We provide datasets from combined ex vivo diffusion tensor imaging (DTI and Clear Lipid-exchanged, Anatomically Rigid, Imaging/immunostaining compatible, Tissue hYdrogel (CLARITY performed on intact mouse brains. DTI-derived measures of fractional anisotropy (FA, radial diffusivity (RD, and axial diffusivity (AD were compared to antibody-based labeling of myelin basic protein (MBP, as measured by fluorescence microscopy. We used a customized CLARITY hydrogel solution to facilitate whole brain tissue clearing and subsequent immunolabeling. We describe how CLARITY was made compatible with magnetic resonance imaging with the intention of facilitating future multimodal imaging studies that may combine noninvasive imaging with 3D immunohistochemistry. These data and methods are related to the accompanying research article entitled, ‘The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains’ (E.H. Chang, M. Argyelan, M. Aggarwal, T-S. Chandon, K.H. Karlsgodt, S. Mori, A.K. Malhotra, 2016 [1].

  17. A calibration strategy in bioimaging trace elements in rat brain tissue by LA ICP-TOF-MS method.

    Science.gov (United States)

    Jurowski, Kamil; Walas, Stanislaw; Piekoszewski, Wojciech

    2013-10-15

    A calibration step in an analytical procedure is often not adequately treated, although it is a very important step in the analysis. Also, the approach to the nomenclature seems to be disrespectful. In order to resolve this problem we chose a new classification based on both how the calibration dependence is reconstructed, and how the measurement data is then transformed. In this paper we discussed the steps of a developed calibration procedure in the determination of trace elements in rat brain tissues by the Laser Ablation Inductively Coupled Plasma Time of Flight Mass Spectrometry (LA ICP-TOF-MS) method. The developed calibration procedure uses the long established calibration method - the method of standard addition - although the standard samples are in this case the rat brain tissue samples. The results show the usefulness of the procedure developed in the presented analytical problem related to the analysis of solid samples, which is where the work is original. © 2013 Elsevier B.V. All rights reserved.

  18. Tissue sensitive imaging and tomography without contrast agents for small animals with Timepix based detectors

    Science.gov (United States)

    Trojanova, E.; Schyns, L. E. J. R.; Ludwig, D.; Jakubek, J.; Le Pape, A.; Sefc, L.; Lotte, S.; Sykora, V.; Turecek, D.; Uher, J.; Verhaegen, F.

    2017-01-01

    The tissue type resolving X-ray radiography and tomography can be performed even without contrast agents. The differences between soft tissue types such as kidney, muscles, fat, liver, brain and spleen were measured based on their spectral response. The Timepix based X-ray imaging detector WidePIX2×5 with 300 μm thick silicon sensors was used for most of the measurements presented in this work. These promising results are used for further optimizations of the detector technology and radiographic methods.

  19. Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

    2015-01-01

    Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

  20. MR-based attenuation correction in brain PET based on UTE sequences

    Energy Technology Data Exchange (ETDEWEB)

    Cabello, Jorge; Nekolla, Stephan G; Ziegler, Sibylle I [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München (Germany)

    2014-07-29

    Attenuation correction (AC) in brain PET/MR has recently emerged as one of the challenging tasks in the PET/MR field. It has been shown that to ignore the attenuation produced by bone can lead to errors ranging from 5-30% in regions close to bone structures. Since the information provided by the MR signal is not directly related to tissue attenuation, alternative methods have to be developed. Signal from bone tissue is difficult to measure given its short transverse relaxation time (T2). Ultrashort-echo time (UTE) pulse sequences were developed to measure signal from tissues with short T2. A combination of two consecutive UTE echoes has been used in several works to measure signal from bone tissue. The first echo is able to measure signal from bone tissue in addition to soft tissue, while the second echo contains most of the soft tissue contained in the first echo but not bone. In this work we extract the attenuation information from the difference between the logarithm of two images obtained after applying two consecutive UTE pulse sequences using the mMR scanner (Siemens Healthcare). Subsequently, image processing techniques are applied to reduce the noise and extract air cavities within the head. The resulting image is converted to linear attenuation coefficients, generating what is known as µ-map, to be used during reconstruction. For comparison purposes PET/CT scans of the same patients were acquired prior to the PET/MR scan. Additional µ-maps obtained for comparison were extracted from a Dixon sequence (used in clinical routine) and an additional µ-map calculated by the scanner based on UTE pulse sequences. Preliminary quantitative results measured in the cerebellum, using the value obtained with CT-based AC as reference, show differences of 34% without AC, 13% using the Dixon-based and UTE-based provided by the scanner, and 0.8% with the AC strategy presented here.

  1. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  2. Diffusion Based Modeling of Human Brain Response to External Stimuli

    CERN Document Server

    Namazi, Hamidreza

    2012-01-01

    Human brain response is the overall ability of the brain in analyzing internal and external stimuli in the form of transferred energy to the mind/brain phase-space and thus, making the proper decisions. During the last decade scientists discovered about this phenomenon and proposed some models based on computational, biological, or neuropsychological methods. Despite some advances in studies related to this area of the brain research there was less effort which have been done on the mathematical modeling of the human brain response to external stimuli. This research is devoted to the modeling of human EEG signal, as an alert state of overall human brain activity monitoring, due to receiving external stimuli, based on fractional diffusion equation. The results of this modeling show very good agreement with the real human EEG signal and thus, this model can be used as a strong representative of the human brain activity.

  3. High-resolution in vivo Wistar rodent brain atlas based on T1 weighted image

    Science.gov (United States)

    Huang, Su; Lu, Zhongkang; Huang, Weimin; Seramani, Sankar; Ramasamy, Boominathan; Sekar, Sakthivel; Guan, Cuntai; Bhakoo, Kishore

    2016-03-01

    Image based atlases for rats brain have a significant impact on pre-clinical research. In this project we acquired T1-weighted images from Wistar rodent brains with fine 59μm isotropical resolution for generation of the atlas template image. By applying post-process procedures using a semi-automatic brain extraction method, we delineated the brain tissues from source data. Furthermore, we applied a symmetric group-wise normalization method to generate an optimized template of T1 image of rodent brain, then aligned our template to the Waxholm Space. In addition, we defined several simple and explicit landmarks to corresponding our template with the well known Paxinos stereotaxic reference system. Anchoring at the origin of the Waxholm Space, we applied piece-wise linear transformation method to map the voxels of the template into the coordinates system in Paxinos' stereotoxic coordinates to facilitate the labelling task. We also cross-referenced our data with both published rodent brain atlas and image atlases available online, methodologically labelling the template to produce a Wistar brain atlas identifying more than 130 structures. Particular attention was paid to the cortex and cerebellum, as these areas encompass the most researched aspects of brain functions. Moreover, we adopted the structure hierarchy and naming nomenclature common to various atlases, so that the names and hierarchy structure presented in the atlas are readily recognised for easy use. It is believed the atlas will present a useful tool in rodent brain functional and pharmaceutical studies.

  4. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2015-01-01

    Full Text Available Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM and white matter (WM using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  5. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C.; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations. PMID:26740917

  6. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  7. Stem Cell-Based Dental Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Petar Zivkovic

    2010-01-01

    Full Text Available The development of biological and biomaterial sciences profiled tissue engineering as a new and powerful tool for biological replacement of organs. The combination of stem cells and suitable scaffolds is widely used in experiments today, in order to achieve partial or whole organ regeneration. This review focuses on the use of tissue engineering strategies in tooth regeneration, using stem cells and stem cells/scaffold constructs. Although whole tooth regeneration is still not possible, there are promising results. However, to achieve this goal, it is important to understand and further explore the mechanisms underlying tooth development. Only then will we be able to mimic the natural processes with the use of stem cells and tissue engineering techniques.

  8. Localization and labeling of rat brain in MR image based on Paxinos-Watson atlas

    Science.gov (United States)

    Cao, Jie; Cai, Chao; Ding, Mingyue; Zhou, Chengping

    2006-03-01

    Localization and labeling of function regions in brain is an important topic in experimental brain sciences because the huge amount of data collected by neuroscientists will become meaningless if we cannot give them a precise description of their locations. In this paper, we proposed a localization and labelling method of 3D MR image of rat brain based on Paxinos-Watson atlas. Our objective is to use the specific atlas to accomplish localization and labeling of specified tissue of interest (TOI) to mimic a veteran expert such that invisible or unclear anatomic function regions in the MR images of rat brain can be automatically identified and marked. We proposed a multi-step method to locate and label the TOIs from the MR image of rat brain. Firstly, pre-processing. It aims at the digitization and 3D reconstruction of the atlas and MRI of rat brain. Secondly, two-step registration. The global registration is to eliminate the big misalign and section angle offset as well as the scale between the MRI and atlas. We can choose some unambiguous and characteristic points manually, and based on these correspondences a coarse registration is obtained using affine model. The local registration is to address individual variability of rat brain that can be performed by using Snake model. Thirdly, post-processing. The goal is to locate and label the TOIs in the selected MR image of rat brain slice guided by well-registered atlas. The experiments demonstrated the feasibility of our method.

  9. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    Science.gov (United States)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  10. Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.

    Science.gov (United States)

    Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

    2013-01-01

    The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two.

  11. Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection

    Directory of Open Access Journals (Sweden)

    Balasubramaniam Vinod RMT

    2012-02-01

    Full Text Available Abstract Background Highly-pathogenic avian influenza (HPAI H5N1 and Newcastle disease (ND viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses. Methods An improved mRNA differential display technique (Gene Fishing™ was undertaken to analyze differentially expressed transcripts regulated during HPAI H5N1 and velogenic neurotropic NDV infections of whole brain of chickens. The identification of differentially expressed genes (DEGs was made possible as this technique uses annealing control primers that generate reproducible, authentic and long PCR products that are detectable on agarose gels. Results Twenty-three genes were identified to be significantly regulated during infections with both viruses, where ten of the genes have been selected for validation using a TaqMan® based real time quantitative PCR assay. Some of the identified genes demonstrated to be key factors involving the cytoskeletal system, neural signal transduction and protein folding during stress. Interestingly, Septin 5, one of the genes isolated from HPAI H5N1-infected brain tissues has been reported to participate in the pathogenic process of Parkinson's disease. Conclusions In this limited study, the differentially expressed genes of infected brain tissues regulated by the viruses were found not to be identical, thus suggesting that their neurovirulence and neuropathogenesis may not share similar mechanisms and pathways.

  12. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  13. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  14. Imaging of non tumorous and tumorous human brain tissue with full-field optical coherence tomography

    CERN Document Server

    Assayag, Osnath; Devaux, Bertrand; Harms, Fabrice; Pallud, Johan; Chretien, Fabrice; Boccara, Claude; Varlet, Pascale

    2013-01-01

    A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\\mum resolution in 3D with a typical 200\\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and brain tumors such as meningiomas, low- grade and high-grade gliomas, and choroid plexus papilloma were imaged. A subpopulation of neurons, myelin fibers and CNS vasculature were clearly identified. Cortex could be discriminated from white matter, but individual glial cells as astrocytes (normal or reactive) or oligodendrocytes were not observable. This study reports for the first time on the feasibility of using FF-OCT in a...

  15. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    Science.gov (United States)

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  16. Robust volume assessment of brain tissues for 3-dimensional fourier transformation MRI via a novel multispectral technique.

    Directory of Open Access Journals (Sweden)

    Jyh-Wen Chai

    Full Text Available A new TRIO algorithm method integrating three different algorithms is proposed to perform brain MRI segmentation in the native coordinate space, with no need of transformation to a standard coordinate space or the probability maps for segmentation. The method is a simple voxel-based algorithm, derived from multispectral remote sensing techniques, and only requires minimal operator input to depict GM, WM, and CSF tissue clusters to complete classification of a 3D high-resolution multislice-multispectral MRI data. Results showed very high accuracy and reproducibility in classification of GM, WM, and CSF in multislice-multispectral synthetic MRI data. The similarity indexes, expressing overlap between classification results and the ground truth, were 0.951, 0.962, and 0.956 for GM, WM, and CSF classifications in the image data with 3% noise level and 0% non-uniformity intensity. The method particularly allows for classification of CSF with 0.994, 0.961 and 0.996 of accuracy, sensitivity and specificity in images data with 3% noise level and 0% non-uniformity intensity, which had seldom performed well in previous studies. As for clinical MRI data, the quantitative data of brain tissue volumes aligned closely with the brain morphometrics in three different study groups of young adults, elderly volunteers, and dementia patients. The results also showed very low rates of the intra- and extra-operator variability in measurements of the absolute volumes and volume fractions of cerebral GM, WM, and CSF in three different study groups. The mean coefficients of variation of GM, WM, and CSF volume measurements were in the range of 0.03% to 0.30% of intra-operator measurements and 0.06% to 0.45% of inter-operator measurements. In conclusion, the TRIO algorithm exhibits a remarkable ability in robust classification of multislice-multispectral brain MR images, which would be potentially applicable for clinical brain volumetric analysis and explicitly promising

  17. Tissue-based map of the human proteome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

    2015-01-01

    transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human......Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative...... secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns...

  18. Detection of Neospora caninum-DNA in brain tissues from pigeons in Changchun, Jilin (China).

    Science.gov (United States)

    Du, Ling; Yang, Dongsheng; Zhai, Tao; Gong, Pengtao; Zhang, Xichen; Li, Jianhua

    2015-11-30

    Neospora caninum is an intracellular protozoan infecting many domestic and wild animals. The domestic chicken (Gallus domesticus) and the sparrow (Passer domesticus) are known as natural intermediate hosts of N. caninum, whereas the role of other birds such as pigeons is still unclear. In the present study, pigeon brain tissues collected in Jilin of China were screened by N. caninum specific-nested PCR to determine whether pigeons functioned as the natural intermediate hosts of N. caninum. The prevalences of N. caninum DNA and Toxoplasma gondii DNA among the brain samples were 30% (63/210) and 13.33% (28/210), respectively. One brain sample was co-infected with N. caninum and T. gondii in naturally infected pigeon. Of the 63 positive samples 42 could be assigned to the NC-PR genotype, 10 to the NC-1 genotypes and 5, 3 and 3 respectively to the each of the three new genotypes identified, indicating genetic polymorphism of N. caninum in pigeons in Jilin of China. The present study expanded the list of intermediate hosts of N. caninum to include pigeons which suggests that pigeons are involved in the transmission of the N. caninum.

  19. A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI.

    Science.gov (United States)

    Schwarz, Adam J; Danckaert, Anne; Reese, Torsten; Gozzi, Alessandro; Paxinos, George; Watson, Charles; Merlo-Pich, Emilio V; Bifone, Angelo

    2006-08-15

    We describe a stereotaxic rat brain MRI template set with a co-registered digital anatomical atlas and illustrate its application to the analysis of a pharmacological MRI (phMRI) study of apomorphine. The template set includes anatomical images and tissue class probability maps for brain parenchyma and cerebrospinal fluid (CSF). These facilitate the use of standard fMRI software for spatial normalisation and tissue segmentation of rat brain data. A volumetric reconstruction of the Paxinos and Watson rat brain atlas is also co-localised with the template, enabling the atlas structure and stereotaxic coordinates corresponding to a feature within a statistical map to be interactively reported, facilitating the localisation of functional effects. Moreover, voxels falling within selected brain structures can be combined to define anatomically based 3D volumes of interest (VOIs), free of operator bias. As many atlas structures are small relative to the typical resolution of phMRI studies, a mechanism for defining composite structures as agglomerations of individual atlas structures is also described. This provides a simple and robust means of interrogating structures that are otherwise difficult to delineate and an objective framework for comparing and classifying compounds based on an anatomical profile of their activity. These developments allow a closer alignment of pre-clinical and clinical analysis techniques.

  20. Spectroscopic magnetic resonance imaging of the brain: voxel localisation and tissue segmentation in the follow up of brain tumour.

    Science.gov (United States)

    Poloni, Guy; Bastianello, S; Vultaggio, Angela; Pozzi, S; Maccabelli, Gloria; Germani, Giancarlo; Chiarati, Patrizia; Pichiecchio, Anna

    2008-01-01

    The field of application of magnetic resonance spectroscopy (MRS) in biomedical research is expanding all the time and providing opportunities to investigate tissue metabolism and function. The data derived can be integrated with the information on tissue structure gained from conventional and non-conventional magnetic resonance imaging (MRI) techniques. Clinical MRS is also strongly expected to play an important role as a diagnostic tool. Essential for the future success of MRS as a clinical and research tool in biomedical sciences, both in vivo and in vitro, is the development of an accurate, biochemically relevant and physically consistent and reliable data analysis standard. Stable and well established analysis algorithms, in both the time and the frequency domain, are already available, as is free commercial software for implementing them. In this study, we propose an automatic algorithm that takes into account anatomical localisation, relative concentrations of white matter, grey matter, cerebrospinal fluid and signal abnormalities and inter-scan patient movement. The endpoint is the collection of a series of covariates that could be implemented in a multivariate analysis of covariance (MANCOVA) of the MRS data, as a tool for dealing with differences that may be ascribed to the anatomical variability of the subjects, to inaccuracies in the localisation of the voxel or slab, or to movement, rather than to the pathology under investigation. The aim was to develop an analysis procedure that can be consistently and reliably applied in the follow up of brain tumour. In this study, we demonstrate that the inclusion of such variables in the data analysis of quantitative MRS is fundamentally important (especially in view of the reduced accuracy typical of MRS measures compared to other MRI techniques), reducing the occurrence of false positives.

  1. Antioxidant effect of sericin in brain and peripheral tissues of oxidative stress induced hypercholesterolemic rats

    Directory of Open Access Journals (Sweden)

    Meetali Deori

    2016-09-01

    Full Text Available This study evaluated the antioxidant effect of crude sericin extract (CSE from Antheraea assamenisis (Aa in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w./day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control (NC, high cholesterol fed (HCF, HCF + 0.065 gm/kg b.w./day fenofibrate (FF, HCF + sericin 0.25 gm/kg b.w./day (LSD and HCF + sericin 0.5 gm/kg b.w./day (HSD. In brain, heart, liver, serum and kidney homogenates nitric oxide (NO, thiobarbituric acid reactive substances (TBARS, protein carbonyl content (PCC, superoxide dismutase (SOD, reduced glutathione (GSH was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress (OS marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

  2. Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress Induced Hypercholesterolemic Rats.

    Science.gov (United States)

    Deori, Meetali; Devi, Dipali; Kumari, Sima; Hazarika, Ankita; Kalita, Himadri; Sarma, Rahul; Devi, Rajlakshmi

    2016-01-01

    This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH) was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC) excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

  3. Segmentation of Brain MRI Using SOM-FCM-Based Method and 3D Statistical Descriptors

    Directory of Open Access Journals (Sweden)

    Andrés Ortiz

    2013-01-01

    Full Text Available Current medical imaging systems provide excellent spatial resolution, high tissue contrast, and up to 65535 intensity levels. Thus, image processing techniques which aim to exploit the information contained in the images are necessary for using these images in computer-aided diagnosis (CAD systems. Image segmentation may be defined as the process of parcelling the image to delimit different neuroanatomical tissues present on the brain. In this paper we propose a segmentation technique using 3D statistical features extracted from the volume image. In addition, the presented method is based on unsupervised vector quantization and fuzzy clustering techniques and does not use any a priori information. The resulting fuzzy segmentation method addresses the problem of partial volume effect (PVE and has been assessed using real brain images from the Internet Brain Image Repository (IBSR.

  4. Brain parcellation based on information theory.

    Science.gov (United States)

    Bonmati, Ester; Bardera, Anton; Boada, Imma

    2017-11-01

    In computational neuroimaging, brain parcellation methods subdivide the brain into individual regions that can be used to build a network to study its structure and function. Using anatomical or functional connectivity, hierarchical clustering methods aim to offer a meaningful parcellation of the brain at each level of granularity. However, some of these methods have been only applied to small regions and strongly depend on the similarity measure used to merge regions. The aim of this work is to present a robust whole-brain hierarchical parcellation that preserves the global structure of the network. Brain regions are modeled as a random walk on the connectome. From this model, a Markov process is derived, where the different nodes represent brain regions and in which the structure can be quantified. Functional or anatomical brain regions are clustered by using an agglomerative information bottleneck method that minimizes the overall loss of information of the structure by using mutual information as a similarity measure. The method is tested with synthetic models, structural and functional human connectomes and is compared with the classic k-means. Results show that the parcellated networks preserve the main properties and are consistent across subjects. This work provides a new framework to study the human connectome using functional or anatomical connectivity at different levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

    Science.gov (United States)

    Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2016-10-01

    Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

  6. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

    Science.gov (United States)

    Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

    2014-04-01

    Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

  7. Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj on brain cerebrum, liver & kidney in rats

    Directory of Open Access Journals (Sweden)

    Gajendra Kumar

    2014-01-01

    Full Text Available Background & objectives: Sidh Makardhwaj (SM is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg, mercuric chloride (1 mg/kg and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA, reduced glutathione (GSH in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin and kidney (serum urea and creatinine function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

  8. A discriminative model-constrained EM approach to 3D MRI brain tissue classification and intensity non-uniformity correction

    Energy Technology Data Exchange (ETDEWEB)

    Wels, Michael; Hornegger, Joachim [Pattern Recognition Lab, Department of Computer Science, Friedrich-Alexander University Erlangen-Nuremberg, Martensstr. 3, 91058 Erlangen (Germany); Zheng Yefeng; Comaniciu, Dorin [Corporate Research and Technologies, Siemens Corporate Technology, 755 College Road East, Princeton, NJ 08540 (United States); Huber, Martin, E-mail: michael.wels@informatik.uni-erlangen.de [Corporate Research and Technologies, Siemens Corporate Technology, Guenther-Scharowsky-Str. 1, 91058 Erlangen (Germany)

    2011-06-07

    We describe a fully automated method for tissue classification, which is the segmentation into cerebral gray matter (GM), cerebral white matter (WM), and cerebral spinal fluid (CSF), and intensity non-uniformity (INU) correction in brain magnetic resonance imaging (MRI) volumes. It combines supervised MRI modality-specific discriminative modeling and unsupervised statistical expectation maximization (EM) segmentation into an integrated Bayesian framework. While both the parametric observation models and the non-parametrically modeled INUs are estimated via EM during segmentation itself, a Markov random field (MRF) prior model regularizes segmentation and parameter estimation. Firstly, the regularization takes into account knowledge about spatial and appearance-related homogeneity of segments in terms of pairwise clique potentials of adjacent voxels. Secondly and more importantly, patient-specific knowledge about the global spatial distribution of brain tissue is incorporated into the segmentation process via unary clique potentials. They are based on a strong discriminative model provided by a probabilistic boosting tree (PBT) for classifying image voxels. It relies on the surrounding context and alignment-based features derived from a probabilistic anatomical atlas. The context considered is encoded by 3D Haar-like features of reduced INU sensitivity. Alignment is carried out fully automatically by means of an affine registration algorithm minimizing cross-correlation. Both types of features do not immediately use the observed intensities provided by the MRI modality but instead rely on specifically transformed features, which are less sensitive to MRI artifacts. Detailed quantitative evaluations on standard phantom scans and standard real-world data show the accuracy and robustness of the proposed method. They also demonstrate relative superiority in comparison to other state-of-the-art approaches to this kind of computational task: our method achieves average

  9. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure

    Directory of Open Access Journals (Sweden)

    E.M. Meintjes

    2014-01-01

    Full Text Available Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD. Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years and controls (n = 16, 9.5–11.0 years. Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1 the thalamus, midbrain, and ventromedial frontal lobe, (2 the superior cerebellum and inferior occipital lobe, (3 the dorsolateral frontal cortex, and (4 the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

  10. Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

    Science.gov (United States)

    Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

    2017-08-01

    Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

  11. Implementation of an absolute brain 1H-MRS quantification method to assess different tissue alterations in multiple sclerosis.

    Science.gov (United States)

    Bagory, Matthieu; Durand-Dubief, Françoise; Ibarrola, Danielle; Comte, Jean-Christophe; Cotton, François; Confavreux, Christian; Sappey-Marinier, Dominique

    2012-10-01

    Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.

  12. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  13. Chicken FTO gene: tissue-specific expression, brain distribution, breed difference and effect of fasting.

    Science.gov (United States)

    Wang, Yufeng; Rao, Kaiqing; Yuan, Lixia; Everaert, Nadia; Buyse, Johan; Grossmann, Roland; Zhao, Ruqian

    2012-11-01

    Fat mass and obesity-associated (FTO) gene is widely expressed in central and peripheral tissues of mammals, and exhibits a range of functions, especially in energy balance. However, basic knowledge of FTO in the chicken is lacking. Therefore, we studied the tissue distribution, age and breed dependent changes, brain localization, as well as the impact of fasting on FTO mRNA expression in the chicken. FTO mRNA was expressed in all the tissues studied, and generally, with high expression in hypothalamus, liver, visceral fat and cerebellum. However it exhibited breed-specific patterns: in broilers, the highest expression was seen in the liver, while in layers, hypothalamus and cerebellum showed relatively higher FTO mRNA expression. One-week-old broilers expressed markedly higher FTO mRNA in liver compared with the layers of the same age (Pbreed difference was reversed in visceral fat and cerebellum (PBreed-specific expression of FTO mRNA was shown in PVN, but not in VMN, with higher abundance in broilers compared to layers. The decrease in FTO mRNA levels after 24h of fasting was seen only in VMN of layer chickens. These results may provide some intriguing hints for further investigation of FTO function in the chicken. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Automatic Tissue Differentiation Based on Confocal Endomicroscopic Images for Intraoperative Guidance in Neurosurgery

    Directory of Open Access Journals (Sweden)

    Ali Kamen

    2016-01-01

    Full Text Available Diagnosis of tumor and definition of tumor borders intraoperatively using fast histopathology is often not sufficiently informative primarily due to tissue architecture alteration during sample preparation step. Confocal laser microscopy (CLE provides microscopic information of tissue in real-time on cellular and subcellular levels, where tissue characterization is possible. One major challenge is to categorize these images reliably during the surgery as quickly as possible. To address this, we propose an automated tissue differentiation algorithm based on the machine learning concept. During a training phase, a large number of image frames with known tissue types are analyzed and the most discriminant image-based signatures for various tissue types are identified. During the procedure, the algorithm uses the learnt image features to assign a proper tissue type to the acquired image frame. We have verified this method on the example of two types of brain tumors: glioblastoma and meningioma. The algorithm was trained using 117 image sequences containing over 27 thousand images captured from more than 20 patients. We achieved an average cross validation accuracy of better than 83%. We believe this algorithm could be a useful component to an intraoperative pathology system for guiding the resection procedure based on cellular level information.

  15. Establishment of a Stable PrPSc Panel from Brain Tissues of Experimental Hamsters with Scrapie Strain 263K

    Institute of Scientific and Technical Information of China (English)

    BAO-YUN ZHANG; CHAN TIAN; JUN HAN; CHEN GAO; QI SHI; JIAN-MING CHEN; HUI-YING JIANG; WEI ZHOU; XIAO-Ping DONG

    2009-01-01

    Objective To establish a stable PrPSc panel from brain tissues of experimental hamsters infected with scrapie agent 263K for evaluating diagnostic techniques of human and animals' prion diseases. Methods Thirty brain tissue samples from hamsters intracerebrally infected with scrapie strain 263K and another 30 samples from normal hamsters were selected to prepare 10%, 1%, and 0.5% brain homogenates, which were aliquoted into stocks. PrPSc in each brain homogenate was determined by proteinase K digestions followed by Western blot assay and partially by immunohistochemistry. Stability and glycoforms of PrPSc were repeatedly detected by PrPSc-specific Western blots in half a year and 3 years later. Results PrPSc signals were observed in all 10% brain homogenates of infected hamsters. Twenty out of 30 stocks and 19 out of 30 stocks were PrPSc positive in 1% and 0.5% brain homogenatesof infected hamsters, respectively. Twenty-seven out of 30 stocks presented three positive bands in 10% brain homogenates, whereas none of 1% and 0.5% homogenates contained 3 bands. The detection of PrPSc-specific signals stored in half a year and 3 years later demonstrated that the ratio of PrPSc positive samples and glycoforms was almost unchanged. All normal hamsters' brain homogenates were PrPSc negative. Conclusion A PrPSc panel of prion disease can be established, which displays reliably stable PrPSc-specific signals and glycoforms.

  16. Fiber optic based multiparametric spectroscopy in vivo: Toward a new quantitative tissue vitality index

    Science.gov (United States)

    Kutai-Asis, Hofit; Barbiro-Michaely, Efrat; Deutsch, Assaf; Mayevsky, Avraham

    2006-02-01

    In our previous publication (Mayevsky et al SPIE 5326: 98-105, 2004) we described a multiparametric fiber optic system enabling the evaluation of 4 physiological parameters as indicators of tissue vitality. Since the correlation between the various parameters may differ in various pathophysiological conditions there is a need for an objective quantitative index that will integrate the relative changes measured in real time by the multiparametric monitoring system into a single number-vitality index. Such an approach to calculate tissue vitality index is critical for the possibility to use such an instrument in clinical environments. In the current presentation we are reporting our preliminary results indicating that calculation of an objective tissue vitality index is feasible. We used an intuitive empirical approach based on the comparison between the calculated index by the computer and the subjective evaluation made by an expert in the field of physiological monitoring. We used the in vivo brain of rats as an animal model in our current studies. The rats were exposed to anoxia, ischemia and cortical spreading depression and the responses were recorded in real time. At the end of the monitoring session the results were analyzed and the tissue vitality index was calculated offline. Mitochondrial NADH, tissue blood flow and oxy-hemoglobin were used to calculate the vitality index of the brain in vivo, where each parameter received a different weight, in each experiment type based on their significance. It was found that the mitochondrial NADH response was the main factor affected the calculated vitality index.

  17. Prediction of drug distribution in subcutaneous xenografts of human tumor cell lines and healthy tissues in mouse: application of the tissue composition-based model to antineoplastic drugs.

    Science.gov (United States)

    Poulin, Patrick; Chen, Yung-Hsiang; Ding, Xiao; Gould, Stephen E; Hop, Cornelis Eca; Messick, Kirsten; Oeh, Jason; Liederer, Bianca M

    2015-04-01

    Advanced tissue composition-based models can predict the tissue-plasma partition coefficient (Kp ) values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on healthy tissues and do not incorporate data from tumors. The objective of this study was to apply a tissue composition-based model to six marketed antineoplastic drugs (docetaxel, DOC; doxorubicin, DOX; gemcitabine, GEM; methotrexate, MTX; topotecan, TOP; and fluorouracil, 5-FU) to predict their Kp values in three human tumor xenografts (HCT-116, H2122, and PC3) as well as in healthy tissues (brain, muscle, lung, and liver) under steady-state in vivo conditions in female NCR nude mice. The mechanisms considered in the tissue/tumor composition-based model are the binding to lipids and to plasma proteins, but the transporter effect was also investigated. The method consisted of analyzing tissue composition, performing the pharmacokinetics studies in mice, and calculating the corresponding in vivo Kp values. Analyses of tumor composition indicated that the tumor xenografts contained no or low amounts of common transporters by contrast to lipids. The predicted Kp values were within twofold and threefold of the measured values in 77% and 93% of cases, respectively. However, predictions for brain for each drug, for liver for MTX, and for each tumor xenograft for GEM were disparate from the observed values, and, therefore, not well served by the model. Overall, this study is the first step toward the mechanism-based prediction of Kp values of small molecules in healthy and tumor tissues in mouse when no transporter and permeation limitation effect is evident. This approach will be useful in selecting compounds based on their abilities to penetrate human cancer xenografts with a physiologically based pharmacokinetic (PBPK) model, thereby increasing therapeutic index for chemotherapy in oncology study. © 2015 Wiley Periodicals, Inc. and the American

  18. An automatic framework for quantitative validation of voxel based morphometry measures of anatomical brain asymmetry.

    Science.gov (United States)

    Pepe, Antonietta; Dinov, Ivo; Tohka, Jussi

    2014-10-15

    The study of anatomical brain asymmetries has been a topic of great interest in the neuroimaging community in the past decades. However, the accuracy of brain asymmetry measurements has been rarely investigated. In this study, we propose a fully automatic methodology for the quantitative validation of brain tissue asymmetries as measured by Voxel Based Morphometry (VBM) from structural magnetic resonance (MR) images. Starting from a real MR image, the methodology generates simulated 3D MR images with a known and realistic pattern of inter-hemispheric asymmetry that models the left-occipital right-frontal petalia of a normal brain and the related rightward bending of the inter-hemispheric fissure. As an example, we generated a dataset of 64 simulated MR images and applied this dataset for the quantitative validation of optimized VBM measures of asymmetries in brain tissue composition. Our results suggested that VBM analysis strongly depended on the spatial normalization of the individual brain images, the selected template space, and the amount of spatial smoothing applied. The most accurate asymmetry detections were achieved by 9-degrees of freedom registration to the symmetrical template space with 4 to 8mm spatial smoothing.

  19. Multi-elemental analysis of brain tissue from healthy Wistar rats using sector field inductively coupled plasma mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Mitchell C. [Molecular Structure and Detection Group, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia); Parsons, Carl H. [School of Biomedical Science, University of Newcastle, Callaghan NSW 2308 (Australia); Calford, Mike B. [School of Biomedical Science, University of Newcastle, Callaghan NSW 2308 (Australia); Nagy-Felsobuki, Ellak I. von [Molecular Structure and Detection Group, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan NSW 2308 (Australia)]. E-mail: ellak@newcastle.edu.au

    2004-09-20

    The normal distribution of a range of elements in the brain tissue of healthy Wistar rats was established using sector field inductively coupled plasma mass spectrometry. A protocol was developed to determine concentrations of Ag, Cd, Hg, Pb, Bi, U, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As and Se in specific brain regions. The concentrations of these elements were determined in the range of 2{+-}1 (e.g. Cr in diencephalon) to 7558{+-}450 ng ml{sup -1} (e.g. Fe in olfactory bulb). The detection limits of the sixteen elements ranged between 5 and 300 pg ml{sup -1}, with U yielding the lowest and Fe the highest value. The validity of the protocol was assessed by the analysis of SRM 1577B Bovine Liver and brain tissue spike recoveries. A principal component analysis was used to reveal elemental patterns of the brain regions.

  20. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients.

    Science.gov (United States)

    Wu, L; Sluiter, A A; Guo, Ho-Fu; Balesar, R A; Swaab, D F; Zhou, Jiang-Ning; Verwer, R W H

    2008-01-01

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control participants with rat embryonic day 14 (E14) neural stem cells. Viability staining based on the exclusion of ethidium bromide by intact plasma membranes showed that there were strikingly more viable cells and fewer dead cells in slices co-cultured with neural stem cells than in untreated slices. The presence of Alzheimer pathology in the brain slices did not influence this effect, although the slices from Alzheimer patients, in general, contained fewer viable cells. Co-culturing with rat E14 fibroblasts did not improve the viability of neurons in the human brain slices. Since the human slices and neural stem cells were separated by a membrane during co-culturing our data show for the first time that neural stem cells release diffusible factors that may improve the survival of aged and degenerating neurons in human brains.

  1. Alginate based scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Valente, J.F.A.; Valente, T.A.M. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Alves, P.; Ferreira, P. [CIEPQPF, Departamento de Engenharia Quimica, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Silva, A. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2012-12-01

    The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays. - Highlights: Black-Right-Pointing-Pointer Design and production of scaffolds for bone tissue regeneration. Black-Right-Pointing-Pointer Microparticle and microfiber alginate scaffolds were produced through a particle aggregation technique; Black-Right-Pointing-Pointer Scaffolds' mechanically and biologically properties were characterized through in vitro studies;.

  2. Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

    Science.gov (United States)

    Ramos, Patrícia; Santos, Agostinho; Pinto, Edgar; Pinto, Nair Rosas; Mendes, Ricardo; Magalhães, Teresa; Almeida, Agostinho

    2016-12-01

    The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4μg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus). Copyright © 2016 Elsevier GmbH. All

  3. Stem cell homing-based tissue engineering using bioactive materials

    Science.gov (United States)

    Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

    2017-06-01

    Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

  4. An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

    Science.gov (United States)

    Karimi, Alireza; Navidbakhsh, Mahdi

    2014-07-01

    There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

  5. The physiological and biochemical bases of functional brain imaging

    OpenAIRE

    2007-01-01

    Functional brain imaging is based on the display of computer-derived images of changes in physiological and/or biochemical functions altered by activation or depression of local functional activities in the brain. This article reviews the physiological and biochemical mechanisms involved.

  6. Enhancing Student Learning with Brain-Based Research

    Science.gov (United States)

    Bonnema, Ted R.

    2009-01-01

    This paper discusses brain-based learning and its relation to classroom instruction. A rapidly growing quantity of research currently exists regarding how the brain perceives, processes, and ultimately learns new information. In order to maximize their teaching efficacy, educators should have a basic understanding of key memory functions in the…

  7. Imaging MALDI MS of Dosed Brain Tissues Utilizing an Alternative Analyte Pre-extraction Approach

    Science.gov (United States)

    Quiason, Cristine M.; Shahidi-Latham, Sheerin K.

    2015-06-01

    Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry has been adopted in the pharmaceutical industry as a useful tool to detect xenobiotic distribution within tissues. A unique sample preparation approach for MALDI imaging has been described here for the extraction and detection of cobimetinib and clozapine, which were previously undetectable in mouse and rat brain using a single matrix application step. Employing a combination of a buffer wash and a cyclohexane pre-extraction step prior to standard matrix application, the xenobiotics were successfully extracted and detected with an 8 to 20-fold gain in sensitivity. This alternative approach for sample preparation could serve as an advantageous option when encountering difficult to detect analytes.

  8. Peripheral tissue-brain interactions in the regulation of food intake.

    Science.gov (United States)

    López, Miguel; Tovar, Sulay; Vázquez, María J; Williams, Lynda M; Diéguez, Carlos

    2007-02-01

    More than 70 years ago the glucostatic, lipostatic and aminostatic hypotheses proposed that the central nervous system sensed circulating levels of different metabolites, changing feeding behaviour in response to the levels of those molecules. In the last 20 years the rapid increase in obesity and associated pathologies in developed countries has involved a substantial increase in the knowledge of the physiological and molecular mechanism regulating body mass. This effort has resulted in the recent discovery of new peripheral signals, such as leptin and ghrelin, as well as new neuropeptides, such as orexins, involved in body-weight homeostasis. The present review summarises research into energy balance, starting from the original classical hypotheses proposing metabolite sensing, through peripheral tissue-brain interactions and coming full circle to the recently-discovered role of hypothalamic fatty acid synthase in feeding regulation. Understanding these molecular mechanisms will provide new pharmacological targets for the treatment of obesity and appetite disorders.

  9. The large shear strain dynamic behaviour of in-vitro porcine brain tissue and a silicone gel model material.

    Science.gov (United States)

    Brands, D W; Bovendeerd, P H; Peters, G W; Wismans, J S

    2000-11-01

    The large strain dynamic behaviour of brain tissue and silicone gel, a brain substitute material used in mechanical head models, was compared. The non-linear shear strain behaviour was characterised using stress relaxation experiments. Brain tissue showed significant shear softening for strains above 1% (approximately 30% softening for shear strains up to 20%) while the time relaxation behaviour was nearly strain independent. Silicone gel behaved as a linear viscoelastic solid for all strains tested (up to 50%) and frequencies up to 461 Hz. As a result, the large strain time dependent behaviour of both materials could be derived for frequencies up to 1000 Hz from small strain oscillatory experiments and application of Time Temperature Superpositioning. It was concluded that silicone gel material parameters are in the same range as those of brain tissue. Nevertheless the brain tissue response will not be captured exactly due to increased viscous damping at high frequencies and the absence of shear softening in the silicone gel. For trend studies and benchmarking of numerical models the gel can be a good model material.

  10. Assessing Antioxidant Capacity in Brain Tissue: Methodologies and Limitations in Neuroprotective Strategies

    Directory of Open Access Journals (Sweden)

    Jennifer E. Slemmer

    2014-10-01

    Full Text Available The number of putative neuroprotective compounds with antioxidant activity described in the literature continues to grow. Although these compounds are validated using a variety of in vivo and in vitro techniques, they are often evaluated initially using in vitro cell culture techniques in order to establish toxicity and effective concentrations. Both in vivo and in vitro methodologies have their respective advantages and disadvantages, including, but not limited to, cost, time, use of resources and technical limitations. This review expands on the inherent benefits and drawbacks of in vitro and in vivo methods for assessing neuroprotection, especially in light of proper evaluation of compound efficacy and neural bioavailability. For example, in vivo studies can better evaluate the effects of protective compounds and/or its metabolites on various tissues, including the brain, in the whole animal, whereas in vitro studies can better discern the cellular and/or mechanistic effects of compounds. In particular, we aim to address the question of appropriate and accurate extrapolation of findings from in vitro experiment-where compounds are often directly applied to cellular extracts, potentially at higher concentrations than would ever cross the blood-brain barrier—to the more complex scenario of neuroprotection due to pharmacodynamics in vivo.

  11. High dose Erythropoietin increases Brain Tissue Oxygen Tension in Severe Vasospasm after Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Helbok Raimund

    2012-06-01

    Full Text Available Abstract Background Vasospasm-related delayed cerebral ischemia (DCI significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH. Erythropoietin (EPO may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2. Methods Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM received systemic EPO therapy (30.000 IU per day for 3 consecutive days for severe cerebral vasospasm. Cerebral perfusion pressure (CPP, mean arterial blood pressure (MAP, intracranial pressure (ICP, PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. Results A total of 22 interventions were analyzed. Median age was 47 years (32–68 and 86 % were female. Three patients (38 % developed DCI. MAP decreased 2 hours after intervention (P btO2 significantly increased over time (P  Conclusions EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation.

  12. [Influence of mastication on the amount of hemoglobin in human brain tissue].

    Science.gov (United States)

    Sasaki, A

    2001-03-01

    The purpose of this study was to investigate the influence of mastication on the amount of hemoglobin in human brain tissue. Nine healthy volunteers (6 males and 3 females) participated in this study. They underwent two tasks: 1) at rest, 2) gum-chewing. In seven of the nine (4 males and 3 females), experimental occlusal interference was applied to the first molar of the mandibule on the habitual masticatory side. They underwent the gum-chewing task. To evaluate the amount of hemoglobin, both the hemoglobin oxygenation state and blood volume during gum-chewing were measured in the frontal region, using near-infrared spectroscopy. The amount of total-hemoglobin (blood volume) and oxyhemoglobin of subjects significantly increased during gum-chewing (p < 0.01). When the subjects finished gum-chewing, both levels returned to the original levels. When experimental occlusal interference was imposed on the subject, the amount of them significantly decreased compared with subjects without experimental occlusal interference (p < 0.05). The results suggested that increases of cerebral blood flow in the frontal region were not due to the mandibular movement, and that human brain activity caused by mastication was not only in the cortical masticatory area but also in the frontal region.

  13. CORPORA AMYLACEA OF BRAIN TISSUE FROM NEURODEGENERATIVE DISEASES ARE STAINED WITH SPECIFIC ANTIFUNGAL ANTIBODIES

    Directory of Open Access Journals (Sweden)

    LUIS eCARRASCO

    2016-03-01

    Full Text Available The origin and potential function of corpora amylacea (CA remains largely unknown. Low numbers of CA are detected in the aging brain of normal individuals but they are abundant in the central nervous system of patients with neurodegenerative diseases. In the present study, we show that CA from patients diagnosed with Alzheimer’s disease (AD contain fungal proteins as detected by immunohistochemistry analyses. Accordingly, CA were labeled with different anti-fungal antibodies at the external surface, whereas the central portion composed of calcium salts contain less proteins. Detection of fungal proteins was achieved using a number of antibodies raised against different fungal species, which indicated cross-reactivity between the fungal proteins present in CA and the antibodies employed. Importantly, these antibodies do not immunoreact with cellular proteins. Additionally, CNS samples from patients diagnosed with amyotrophic lateral sclerosis (ALS and Parkinson’s disease (PD also contained CA that were immunoreactive with a range of antifungal antibodies. However, CA were less abundant in ALS or PD patients as compared to CNS samples from AD. By contrast, CA from brain tissue of control subjects were almost devoid of fungal immunoreactivity. These observations are consistent with the concept that CA associate with fungal infections and may contribute to the elucidation of the origin of CA.

  14. Decoding Brain States Based on Magnetoencephalography From Prespecified Cortical Regions.

    Science.gov (United States)

    Zhang, Jinyin; Li, Xin; Foldes, Stephen T; Wang, Wei; Collinger, Jennifer L; Weber, Douglas J; Bagić, Anto

    2016-01-01

    Brain state decoding based on whole-head MEG has been extensively studied over the past decade. Recent MEG applications pose an emerging need of decoding brain states based on MEG signals originating from prespecified cortical regions. Toward this goal, we propose a novel region-of-interest-constrained discriminant analysis algorithm (RDA) in this paper. RDA integrates linear classification and beamspace transformation into a unified framework by formulating a constrained optimization problem. Our experimental results based on human subjects demonstrate that RDA can efficiently extract the discriminant pattern from prespecified cortical regions to accurately distinguish different brain states.

  15. Ontology-based, Tissue MicroArray oriented, image centered tissue bank

    Directory of Open Access Journals (Sweden)

    Viti Federica

    2008-04-01

    Full Text Available Abstract Background Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information. Results In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data. Conclusions Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.

  16. Virtual microstructural leaf tissue generation based on cell growth modeling

    NARCIS (Netherlands)

    Abera, M.K.; Retta, M.A.; Verboven, P.; Nicolai, B.M.; Berghuijs, H.; Struik, P.

    2016-01-01

    A cell growth algorithm for virtual leaf tissue generation is presented based on the biomechanics of plant cells in tissues. The algorithm can account for typical differences in epidermal layers, palisade mesophyll layer and spongy mesophyll layer which have characteristic differences in the shap

  17. Simultaneous analysis of diazepam and its metabolites in rat plasma and brain tissue by HPLC-UV and SPE.

    Science.gov (United States)

    Mercolini, Laura; Mandrioli, Roberto; Iannello, Carmelina; Matrisciano, Francesco; Nicoletti, Ferdinando; Raggi, Maria Augusta

    2009-11-15

    Diazepam is frequently used as an adjuvant during antidepressant therapy. Recently, some studies have suggested that the treatment with benzodiazepines could have different efficacy in depressed patients as opposed to non-depressed ones. To clarify the matter, a study is currently underway, regarding the drug metabolism in rats. In order to obtain a more complete and significant set of data, the main diazepam metabolites have also been considered, namely: nordiazepam, temazepam and oxazepam. A feasible and reliable HPLC method has been developed for the simultaneous determination of these compounds in plasma and brain tissue of rats. The method has been applied to "normal" rats and to genetic rat models of depression in order to estimate drug metabolism in different breeds. Analyte separation was achieved on a C8 reversed phase column using an acidic phosphate buffer/acetonitrile mixture as the mobile phase. The detection wavelength was 238 nm. An original sample pre-treatment, based on solid-phase extraction (SPE) was developed in order to eliminate endogenous interference, using only 250 microL of matrix (brain homogenate or plasma) for a complete analysis. The method has been validated with good results in terms of precision, extraction yield, sensitivity, selectivity and accuracy on both matrices and has been successfully applied to samples from some rats subjected to the preliminary study. The obtained data will hopefully contribute to the clarification of possible differences between depressed and non-depressed subjects with respect to benzodiazepine biotransformation.

  18. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies.

    Science.gov (United States)

    Yaqub, Maqsood; van Berckel, Bart N M; Schuitemaker, Alie; Hinz, Rainer; Turkheimer, Federico E; Tomasi, Giampaolo; Lammertsma, Adriaan A; Boellaard, Ronald

    2012-08-01

    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[(11)C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMV(b)). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (V(b)) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V(b) in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V(b) within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[(11)C]PK11195 neurodegeneration studies.

  19. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies

    Science.gov (United States)

    Yaqub, Maqsood; van Berckel, Bart NM; Schuitemaker, Alie; Hinz, Rainer; Turkheimer, Federico E; Tomasi, Giampaolo; Lammertsma, Adriaan A; Boellaard, Ronald

    2012-01-01

    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[11C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMVb). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (Vb) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of Vb in RPM improved both parametric images and binding potential contrast between groups. Incorporation of Vb within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[11C]PK11195 neurodegeneration studies. PMID:22588187

  20. Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering

    CERN Document Server

    Sultana, Naznin

    2013-01-01

    This book addresses the principles, methods and applications of biodegradable polymer based scaffolds for bone tissue engineering. The general principle of bone tissue engineering is reviewed and the traditional and novel scaffolding materials, their properties and scaffold fabrication techniques are explored. By acting as temporary synthetic extracellular matrices for cell accommodation, proliferation, and differentiation, scaffolds play a pivotal role in tissue engineering. This book does not only provide the comprehensive summary of the current trends in scaffolding design but also presents the new trends and directions for scaffold development for the ever expanding tissue engineering applications.

  1. Cost-effective elimination of lipofuscin fluorescence from formalin-fixed brain tissue by white phosphor light emitting diode array.

    Science.gov (United States)

    Sun, Yulong; Chakrabartty, Avi

    2016-12-01

    Autofluorescence of aldehyde-fixed tissues greatly hinders fluorescence microscopy. In particular, lipofuscin, an autofluorescent component of aged brain tissue, complicates fluorescence imaging of tissue in neurodegenerative diseases. Background and lipofuscin fluorescence can be reduced by greater than 90% through photobleaching using white phosphor light emitting diode arrays prior to treatment with fluorescent probes. We compared the effect of photobleaching versus established chemical quenchers on the quality of fluorescent staining in formalin-fixed brain tissue of frontotemporal dementia with tau-positive inclusions. Unlike chemical quenchers, which reduced fluorescent probe signals as well as background, photobleaching treatment had no effect on probe fluorescence intensity while it effectively reduced background and lipofuscin fluorescence. The advantages and versatility of photobleaching over established methods are discussed.

  2. The in vivo distribution of brain tissue loss in Richardson's syndrome and PSP-parkinsonism: a VBM-DARTEL study.

    Science.gov (United States)

    Agosta, Federica; Kostić, Vladimir S; Galantucci, Sebastiano; Mesaros, Sarlota; Svetel, Marina; Pagani, Elisabetta; Stefanova, Elka; Filippi, Massimo

    2010-08-01

    In this study, we wished to test, using magnetic resonance imaging and voxel-based morphometry (VBM), whether specific cortical and subcortical patterns of brain grey (GM) and white matter (WM) tissue loss can be detected in patients with Richardson's syndrome (PSP-RS) and progressive supranuclear palsy-parkinsonism (PSP-P), and possibly account for their clinical heterogeneity. Twenty patients with PSP, classified as PSP-RS (10 patients) or PSP-P (10 patients), and 24 healthy controls were studied. The Statistical Parametric Mapping (SPM5) and the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra method were used to perform a VBM analysis. Compared with controls, both patient groups showed GM loss in the central midbrain, cerebellar lobes, caudate nuclei, frontotemporal cortices and right hippocampus. WM loss was detected in both conditions in the midbrain, left superior cerebellar peduncle, internal capsulae, and left premotor and bilateral prefrontal regions. Compared with PSP-P, patients with PSP-RS showed additional regions of GM loss in the midbrain, left cerebellar lobe and dentate nuclei. PSP-RS was also associated with a more severe WM loss in the midbrain, internal capsulae, and orbitofrontal, prefrontal and precentral/premotor regions, bilaterally. Patients with PSP-P showed a more pronounced GM loss only in the frontal cortex, bilaterally. This study shows that, albeit the overall pattern of brain atrophy associated with PSP appears remarkably consistent across the spectrum of clinical features recorded in life, major anatomical differences between these two conditions do exist. Such a different topographical distribution of tissue damage may account for the clinical differences between PSP-RS and PSP-P.

  3. Nanobiotechnology-based drug delivery in brain targeting.

    Science.gov (United States)

    Dinda, Subas C; Pattnaik, Gurudutta

    2013-01-01

    Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity

  4. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

    Science.gov (United States)

    Fujiu, Katsuhito; Shibata, Munehiko; Nakayama, Yukiteru; Ogata, Fusa; Matsumoto, Sahohime; Noshita, Koji; Iwami, Shingo; Nakae, Susumu; Komuro, Issei; Nagai, Ryozo; Manabe, Ichiro

    2017-05-01

    Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6C(lo) macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6C(lo) macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

  5. Sources of technical variability in quantitative LC-MS proteomics: human brain tissue sample analysis.

    Science.gov (United States)

    Piehowski, Paul D; Petyuk, Vladislav A; Orton, Daniel J; Xie, Fang; Moore, Ronald J; Ramirez-Restrepo, Manuel; Engel, Anzhelika; Lieberman, Andrew P; Albin, Roger L; Camp, David G; Smith, Richard D; Myers, Amanda J

    2013-05-03

    To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE cleanup (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) > instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its suitability for discovery proteomics studies is demonstrated.

  6. Quantitative comparison of preparation methodologies for X-ray fluorescence microscopy of brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    James, Simon A.; Sexton, Brett A.; Hoobin, Pamela; Mayo, Sheridan C. [CSIRO, Materials Science and Engineering and the Preventative Health Flagship, Clayton, VIC (Australia); Myers, Damian E. [St. Vincent s Hospital, Department of Surgery/Orthopaedics, Fitzroy, VIC (Australia); University of Melbourne, Department of Surgery, Parkville, VIC (Australia); Jonge, Martin D. de; Paterson, David; Howard, Daryl L. [Australian Synchrotron, Clayton, VIC (Australia); Vogt, Stefan [Argonne National Laboratory, X-ray Science Division, Argonne, IL (United States); Ryan, Chris G. [CSIRO, Earth Science and Resources Engineering, Clayton, VIC (Australia); University of Melbourne, School of Physics, Parkville, VIC (Australia); University of Tasmania, CODES Centre of Excellence, Hobart, TAS (Australia); Altissimo, Matteo [Melbourne Centre for Nanofabrication, Clayton, VIC (Australia); Moorhead, Gareth F. [CSIRO, Materials Science and Engineering and the Preventative Health Flagship, Clayton, VIC (Australia); University of Melbourne, School of Physics, Parkville, VIC (Australia); Wilkins, Stephen W. [CSIRO, Materials Science and Engineering and the Preventative Health Flagship, Clayton, VIC (Australia); Monash University, School of Physics, Clayton, VIC (Australia)

    2011-08-15

    X-ray fluorescence microscopy (XFM) facilitates high-sensitivity quantitative imaging of trace metals at high spatial resolution over large sample areas and can be applied to a diverse range of biological samples. Accurate determination of elemental content from recorded spectra requires proper calibration of the XFM instrument under the relevant operating conditions. Here, we describe the manufacture, characterization, and utilization of multi-element thin-film reference foils for use in calibration of XFM measurements of biological and other specimens. We have used these internal standards to assess the two-dimensional distribution of trace metals in a thin tissue section of a rat hippocampus. The data used in this study was acquired at the XFM beamline of the Australian Synchrotron using a new 384-element array detector (Maia) and at beamline 2-ID-E at the Advanced Photon Source. Post-processing of samples by different fixation techniques was investigated, with the conclusion that differences in solvent type and sample handling can significantly alter elemental content. The present study highlights the quantitative capability, high statistical power, and versatility of the XFM technique for mapping trace metals in biological samples, e.g., brain tissue samples in order to help understand neurological processes, especially when implemented in conjunction with a high-performance detector such as Maia. (orig.)

  7. Sources of Technical Variability in Quantitative LC-MS Proteomics: Human Brain Tissue Sample Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Piehowski, Paul D.; Petyuk, Vladislav A.; Orton, Daniel J.; Xie, Fang; Moore, Ronald J.; Ramirez Restrepo, Manuel; Engel, Anzhelika; Lieberman, Andrew P.; Albin, Roger L.; Camp, David G.; Smith, Richard D.; Myers, Amanda J.

    2013-05-03

    To design a robust quantitative proteomics study, an understanding of both the inherent heterogeneity of the biological samples being studied as well as the technical variability of the proteomics methods and platform is needed. Additionally, accurately identifying the technical steps associated with the largest variability would provide valuable information for the improvement and design of future processing pipelines. We present an experimental strategy that allows for a detailed examination of the variability of the quantitative LC-MS proteomics measurements. By replicating analyses at different stages of processing, various technical components can be estimated and their individual contribution to technical variability can be dissected. This design can be easily adapted to other quantitative proteomics pipelines. Herein, we applied this methodology to our label-free workflow for the processing of human brain tissue. For this application, the pipeline was divided into four critical components: Tissue dissection and homogenization (extraction), protein denaturation followed by trypsin digestion and SPE clean-up (digestion), short-term run-to-run instrumental response fluctuation (instrumental variance), and long-term drift of the quantitative response of the LC-MS/MS platform over the 2 week period of continuous analysis (instrumental stability). From this analysis, we found the following contributions to variability: extraction (72%) >> instrumental variance (16%) > instrumental stability (8.4%) > digestion (3.1%). Furthermore, the stability of the platform and its’ suitability for discovery proteomics studies is demonstrated.

  8. The effects of perinatal protein malnutrition on spatial learning and memory behaviour and brain-derived neurotrophic factor concentration in the brain tissue in young rats.

    Science.gov (United States)

    Wang, Ling; Xu, Ruo-Jun

    2007-01-01

    This study aimed to investigate the effects of perinatal protein malnutrition on brain derived-neurotrophic factor (BDNF) concentration in brain tissue and spatial learning and memory performance in young rats. Nine pregnant Wistar rats were assigned into three groups. Rats in one group were fed with a control diet containing 20% protein. Rats in remaining two groups were fed with a diet containing 6% protein from gestation day eight and day 15 respectively till four weeks after birth. At four weeks of age, the rat pups were evaluated for spatial learning ability using Morris Water Maze (MWM) task. At the end of the behaviour tests, rat pups were sacrificed and the brain tissue samples were collected for measurement of total protein and BDNF concentrations. It was found that rat pups fed the low protein diet had lower body weight and slightly lighter brain compared to the control pups. Total protein levels in hippocampus and cerebral cortex were significantly lower in malnourished pups than the controls. The concentration of BDNF in the hippocampus was also significantly lower in rat pups suffered protein malnutrition from early pregnancy than in the controls. MWM tests showed that perinatal protein deprivation, particularly from early pregnancy, significantly impaired learning and memory ability. The results of the present study indicate that perinatal protein malnutrition had adverse influence on spatial navigation and brain BDNF levels in rats. The decreased hippocampal BDNF concentration might partially contribute to the poor learning memory performance in the protein deprived rats.

  9. Aluminium, iron and copper in human brain tissues donated to the Medical Research Council's Cognitive Function and Ageing Study.

    Science.gov (United States)

    House, Emily; Esiri, Margaret; Forster, Gill; Ince, Paul G; Exley, Christopher

    2012-01-01

    Aluminium, iron and copper are all implicated in the aetiology of neurodegenerative diseases including Alzheimer's disease. However, there are very few large cohort studies of the content of these metals in aged human brains. We have used microwave digestion and TH GFAAS to measure aluminium, iron and copper in the temporal, frontal, occipital and parietal lobes of 60 brains donated to the Cognitive Function and Ageing Study. Every precaution was taken to reduce contamination of samples and acid digests to a minimum. Actual contamination was estimated by preparing a large number of (170+) method blanks which were interspersed within the full set of 700+ tissue digests. Subtraction of method blank values (MBV) from tissue digest values resulted in metal contents in all tissues in the range, MBV to 33 μg g(-1) dry wt. for aluminium, 112 to 8305 μg g(-1) dry wt. for iron and MBV to 384 μg g(-1) dry wt. for copper. While the median aluminium content for all tissues was 1.02 μg g(-1) dry wt. it was informative that 41 brains out of 60 included at least one tissue with an aluminium content which could be considered as potentially pathological (> 3.50 μg g(-1) dry wt.). The median content for iron was 286.16 μg g(-1) dry wt. and overall tissue iron contents were generally high which possibly reflected increased brain iron in ageing and in neurodegenerative disease. The median content for copper was 17.41 μg g(-1) dry wt. and overall tissue copper contents were lower than expected for aged brains but they were commensurate with aged brains showing signs of neurodegenerative disease. In this study we have shown, in particular, the value of carrying out significant numbers of method blanks to identify unknown sources of contamination. When these values are subtracted from tissue digest values the absolute metal contents could be considered as conservative and yet they may still reflect aspects of ageing and neurodegenerative disease in individual brains.

  10. Sex- and Tissue-Specific Methylome Changes in Brains of Mice Perinatally Exposed to Lead

    Science.gov (United States)

    Sánchez-Martín, Francisco Javier; Lindquist, Diana M.; Landero-Figueroa, Julio; Zhang, Xiang; Chen, Jing; Cecil, Kim M.; Medvedovic, Mario; Puga, Alvaro

    2014-01-01

    Changes in DNA methylation and subsequent changes in gene expression regulation are the hallmarks of age- and tissue-dependent epigenetic drift and plasticity resulting from the combinatorial integration of genetic determinants and environmental cues. To determine whether perinatal lead exposure caused persistent DNA methylation changes in target tissues, we exposed mouse dams to 0, 3 or 30 ppm of lead acetate in drinking water for a period extending from 2 months prior to mating, through gestation, until weaning of pups at postnatal day-21, and analyzed whole-genome DNA methylation in brain cortex and hippocampus of 2-month old exposed and unexposed progeny. Lead exposure resulted in hypermethylation of three differentially methylated regions in the hippocampus of females, but not males. These regions mapped to Rn4.5s, Sfi1, and Rn45s loci in mouse chromosomes 2, 11 and 17, respectively. At a conservative fdr<0.001, 1,623 additional CpG sites were differentially methylated in female hippocampus, corresponding to 117 unique genes. Sixty of these genes were tested for mRNA expression and showed a trend towards negative correlation between mRNA expression and methylation in exposed females but not males. No statistically significant methylome changes were detected in male hippocampus or in cortex of either sex. We conclude that exposure to lead during embryonic life, a time when the organism is most sensitive to environmental cues, appears to have a sex- and tissue-specific effect on DNA methylation that may produce pathological or physiological deviations from the epigenetic plasticity operative in unexposed mice. PMID:25530354

  11. Joint source based analysis of multiple brain structures in studying major depressive disorder

    Science.gov (United States)

    Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

    2014-03-01

    We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

  12. Tissue-based environmental quality benchmarks and standards.

    Science.gov (United States)

    Meador, James P; Warne, Michael St J; Chapman, Peter M; Chan, King Ming; Yu, Shen; Leung, Kenneth M Y

    2014-01-01

    Although the use of tissue concentrations (residues) of chemical contaminants as the dose metric to characterize chemical toxicity to aquatic organisms has been gaining acceptance over the past 20 years, tissue concentrations are less commonly used in water quality management and have yet to be formally adopted as benchmarks or environmental quality standards (EQS). This synthesis paper addresses advantages and disadvantages for the development and application of tissue-based EQS as an alternative and supplement to exposure-based EQS determined with water and sediment concentration data. Tissue-based EQS can be readily developed in parallel with conventional toxicity tests, and achieved by quantification of chemical concentrations in tissue alongside traditional concentration-response toxicity testing. Tissue-residue toxicity metrics can be used as benchmarks for screening and monitoring water and sediment quality, to derive equivalent water or sediment EQS, and for ecological risk assessments and weight of evidence approaches for assessing ecosystem impairment. Tissue-based toxicity metrics and associated EQS provide several advantages; however, there are some limitations to consider and key knowledge gaps to fill.

  13. Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders.

    Science.gov (United States)

    Horiuchi, Yasue; Kano, Shin-Ichi; Ishizuka, Koko; Cascella, Nicola G; Ishii, Seiji; Talbot, C Conover; Jaffe, Andrew E; Okano, Hideyuki; Pevsner, Jonathan; Colantuoni, Carlo; Sawa, Akira

    2013-12-01

    Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a good surrogate system to address brain disease-associated molecular changes. Nonetheless, whether use of this experimental strategy is justified remains unclear. Here we compared expression profiles of olfactory cells systematically with those from the brain tissues and other cells. Principal component analysis indicated that the expression profiles of olfactory cells are very different from those of blood cells, but are closer to those of stem cells, in particular mesenchymal stem cells, that can be differentiated into the cells of the central nervous system.

  14. Joint learning and weighting of visual vocabulary for bag-of-feature based tissue classification

    KAUST Repository

    Wang, Jim Jing-Yan

    2013-12-01

    Automated classification of tissue types of Region of Interest (ROI) in medical images has been an important application in Computer-Aided Diagnosis (CAD). Recently, bag-of-feature methods which treat each ROI as a set of local features have shown their power in this field. Two important issues of bag-of-feature strategy for tissue classification are investigated in this paper: the visual vocabulary learning and weighting, which are always considered independently in traditional methods by neglecting the inner relationship between the visual words and their weights. To overcome this problem, we develop a novel algorithm, Joint-ViVo, which learns the vocabulary and visual word weights jointly. A unified objective function based on large margin is defined for learning of both visual vocabulary and visual word weights, and optimized alternately in the iterative algorithm. We test our algorithm on three tissue classification tasks: classifying breast tissue density in mammograms, classifying lung tissue in High-Resolution Computed Tomography (HRCT) images, and identifying brain tissue type in Magnetic Resonance Imaging (MRI). The results show that Joint-ViVo outperforms the state-of-art methods on tissue classification problems. © 2013 Elsevier Ltd.

  15. The evaluation of brain CBF and mitochondrial function by a fiber optic tissue spectroscope in neurosurgical patients.

    Science.gov (United States)

    Mayevsky, A; Ornstein, E; Meilin, S; Razon, N; Ouaknine, G E

    2002-01-01

    The brain of neurosurgical patients are exposed to various manipulations in the ICU or during surgery. Under such conditions brain O2 balance may become negative and as a result brain vitality and function will deteriorate. In order to evaluate brain vitality in real time it is important to measure more than one parameter. The multiparametric monitoring system used in our previous study to monitor comatose patients (Mayevsky et al., Brain Res. 740: 268-274, 1996) was changed into a "simplified" tissue spectroscope for real time monitoring of brain O2 balance. Mitochondrial function was evaluated by monitoring the NADH redox state by surface fluorometry. Microcirculatory blood flow was assessed by laser Doppler flowmetry. The combined optical probe was located on the surface of the brain during various neurosurgical procedures and the responses were recorded and presented in real time to the surgeon. A total of 32 patients were monitored during various procedures. The results could be summarized as follows: 1. Hypercapnia led to 3 different types of responses. In two patients the 'stealing' like event was recorded. In the other 7 patients the responses to high CO2 was not detectable. In the last group of 6 patients a clear CBF elevation was recorded with variable response of mitochondrial NADH. 2. Our monitoring device was able to evaluate the efficacy of the STA-MCA anastomosis during aneurysm surgery. 3. A significant correlation was recorded between CBF and NADH redox state during changes in blood pressure, papaverine injection, spontaneous drop in blood supply to the brain or during releasing of high ICP levels. We conclude that in order to evaluate the metabolic state of the brain during neurosurgical procedures it is necessary to monitor both CBF and mitochondrial NADH by using the tissue spectroscope.

  16. Neospora caninum and Toxoplasma gondii in brain tissue of feral rodents and insectivores caught on farms in the Netherlands

    NARCIS (Netherlands)

    Meerburg, B.G.; Craeye, de S.; Dierick, K.; Kijlstra, A.

    2012-01-01

    We investigated the presence of both Neospora caninum and Toxoplasma gondii in 250 brain tissue samples from 9 species of feral rodents and insectivores caught on 10 organic farms in the Netherlands in 2004. Collected samples were conserved in 4% paraformaldehyde solution and analysed by real-time P

  17. Weak mitochondrial targeting sequence determines tissue-specific subcellular localization of glutamine synthetase in liver and brain cells.

    NARCIS (Netherlands)

    Matthews, G.D.; Gur, N.; Koopman, W.J.H.; Pines, O.; Vardimon, L.

    2010-01-01

    Evolution of the uricotelic system for ammonia detoxification required a mechanism for tissue-specific subcellular localization of glutamine synthetase (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and cytoplasmic in brain. Because these species contain a single copy of the GS

  18. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  19. Contents of myelin-basic protein and S-100 in serum and brain tissue of neonatal rats with intrauterine infection-caused brain injury

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Li; Hongying Li; Zhihai Lu

    2006-01-01

    BACKGROUND: The change of the content of myelin basic protein (MBP) in serum and brain tissue is the bio chemical diadynamic index of amyelination. S-100 is a specific and sensitive marker of central nervous system (CNS) injury. Whether or not the content of S-100 and MBP in blood and brain tissue can be used as the quan titative index for early diagnosing the intrauterine infection-caused brain injury still needs investigation. OBJECTIVE: To observe whether or not MBP and S-100 detection can be used as the biochemical indexes for early diagnosing the intrauterine infection-caused brain injury. DESIGN: Randomized controlled animal experiment. SETTING: Laboratory of Pediatric Neuro-rehabilitation, Medical College of Rehabilitation, Jiamusi University. MATERIALS: Sixty female and thirty male common Wistar rats, weighing from 180 to 240 g, were provided by the Experimental Animal Center of Jiamusi University. Reagent: Lipopolysaccharide(LPS, serological type 055: B5, SIGMA Company of USA); MBP enzyme linked immunosobent assay (ELISA) immunoreagent kit (Preclinicai Recombination DNA Laboratory, Chengdu Huaxi Medical Center, Sichuan Province); S-100 ELISA immunoreagent kit ( Department of Physiology, the Fourth Military Medical University of Chinese PLA) and bovine serum albumin(Haitaike Biotechnology Co.,Ltd.).METHODS: This experiment was carried out in the Laboratory of Pediatric Neuro-Rehabilitation, Experimental Animal Center, Department of Pathology and Central Laboratory of Jiamusi University from July 2005 to March 2006. ① Preparation of models and grouping: The female and male rats were placed in one cage at 2: 1 at 17:00 o'clock. Vaginal smear was checked at 8:00 on the next morning. Sperm was found and 0 day of pregnancy was recorded. Pregnant rats were bred in another cage. The pregnant 47 rats were randomly divided into 2 groups: control group (n =10) and experimental group (n =37). The experimental pregnant rats were intraperitoneally injected with LPS

  20. Relationship between Concentrations of Lutein and StARD3 among Pediatric and Geriatric Human Brain Tissue.

    Directory of Open Access Journals (Sweden)

    Jirayu Tanprasertsuk

    Full Text Available Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and cognitive health have been poorly evaluated at a molecular level. The objective of this study was to evaluate the cross-sectional relationship between concentrations of brain lutein and StARD3 (identified as its binding protein in retinal tissue among three age groups: infants (1-4 months, n = 10, older adults (55-86 years, n = 8, and centenarians (98-105 years, n = 10. Brain lutein concentrations were analyzed by high-performance liquid chromatography and StARD3 levels were analyzed by Western Blot analysis. The strong relationship in infant brains (r = 0.75, P 0.05, seven of whom had mild cognitive impairment (MCI or dementia. These exploratory findings suggest an age-related decrease or abnormality of StARD3 activity in human brain. Given that StARD3 is also involved in cholesterol transportation, a process that is aberrant in neurodegenerative diseases, the potential protective function of lutein against these diseases remains to be explored.

  1. Texture analysis in quantitative MR imaging. Tissue characterisation of normal brain and intracranial tumours at 1.5 T

    DEFF Research Database (Denmark)

    Kjaer, L; Ring, P; Thomsen, C

    1995-01-01

    of common first-order and second-order grey level statistics. Tissue differentiation in the images was estimated by the presence or absence of significant differences between tissue types. A fine discrimination was obtained between white matter, cortical grey matter, and cerebrospinal fluid in the normal...... brain, and white matter was readily separated from the tumour lesions. Moreover, separation of solid tumour tissue and peritumoural oedema was suggested for some tumour types. Mutual comparison of all tumour types revealed extensive differences, and even specific tumour differentiation turned out...

  2. Cell-Based Strategies for Meniscus Tissue Engineering

    Science.gov (United States)

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  3. Cell-Based Strategies for Meniscus Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Wei Niu

    2016-01-01

    Full Text Available Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering.

  4. Research of electrosurgical ablation with antiadhesive functionalization on thermal and histopathological effects of brain tissues in vivo.

    Science.gov (United States)

    Hsiao, Wen-Tien; Kung, Chun-Ming; Chu, Jan-Show; Ou, Keng-Liang; Peng, Pei-Wen

    2014-01-01

    Thermal injury and tissue sticking are two major concerns in the electrosurgery. In the present study, the effect of lateral thermal injury caused by different electrosurgical electrodes on wound healing was investigated. An electrosurgical unit equipped with untreated (SS) and titanium oxide layer-coated (TiO2-coated) stainless steel needle-type electrodes was used to create lesions on the rat brain tissue. TiO2 layers were produced by radiofrequency plasma and magnetron sputtering in the form of amorphous (TO-SS-1), anatase (TO-SS-2), and rutile (TO-SS-3) phase. Animals were sacrificed for evaluations at 0, 2, 7, and 28 days postoperatively. TO-SS-3 electrodes generated lower levels of sticking tissue, and the thermographs showed that the recorded highest temperature in brain tissue from the TO-SS-3 electrode was significantly lower than in the SS electrode. The total injury area of brain tissue caused by TO-SS-1 and TO-SS-3 electrodes was significantly lower than that caused by SS electrodes at each time point. The results of the present study reveal that the plating of electrodes with a TiO2 film with rutile phases is an efficient method for improving the performance of electrosurgical units and should benefit wound healing.

  5. Research of Electrosurgical Ablation with Antiadhesive Functionalization on Thermal and Histopathological Effects of Brain Tissues In Vivo

    Directory of Open Access Journals (Sweden)

    Wen-Tien Hsiao

    2014-01-01

    Full Text Available Thermal injury and tissue sticking are two major concerns in the electrosurgery. In the present study, the effect of lateral thermal injury caused by different electrosurgical electrodes on wound healing was investigated. An electrosurgical unit equipped with untreated (SS and titanium oxide layer-coated (TiO2-coated stainless steel needle-type electrodes was used to create lesions on the rat brain tissue. TiO2 layers were produced by radiofrequency plasma and magnetron sputtering in the form of amorphous (TO-SS-1, anatase (TO-SS-2, and rutile (TO-SS-3 phase. Animals were sacrificed for evaluations at 0, 2, 7, and 28 days postoperatively. TO-SS-3 electrodes generated lower levels of sticking tissue, and the thermographs showed that the recorded highest temperature in brain tissue from the TO-SS-3 electrode was significantly lower than in the SS electrode. The total injury area of brain tissue caused by TO-SS-1 and TO-SS-3 electrodes was significantly lower than that caused by SS electrodes at each time point. The results of the present study reveal that the plating of electrodes with a TiO2 film with rutile phases is an efficient method for improving the performance of electrosurgical units and should benefit wound healing.

  6. Changes of learning and memory ability associated with neuronal nitric oxide synthase in brain tissues of rats with acute alcoholism

    Institute of Scientific and Technical Information of China (English)

    Shuang Li; Chunyang Xu; Dongliang Li; Xinjuan Li; Linyu Wei; Yuan Cheng

    2006-01-01

    BACKGROUD: Ethanol can influence neural development and the ability of learning and memory, but its mechanism of the neural toxicity is not clear till now. Endogenous nitric oxide (NO) as a gaseous messenger is proved to play an important role in the formation of synaptic plasticity, transference of neuronal information and the neural development, but excessive nitro oxide can result in neurotoxicity.OBJECTIVE: To observe the effects of acute alcoholism on the learning and memory ability and the content of neuronal nitric oxide synthase (nNOS) in brain tissue of rats.DESIGN: A randomized controlled animal experiment.SETTING: Department of Physiology, Xinxiang Medical College.MATERIALS; Eighteen male clean-degree SD rats of 18-22 weeks were raised adaptively for 2 days, and then randomly divided into control group (n = 8) and experimental group (n = 10). The nNOS immunohistochemical reagent was provided by Beijing Zhongshan Golden Bridge Biotechnology Co.,Ltd. Y-maze was produced by Suixi Zhenghua Apparatus Plant.METHODS: The experiment was carried out in the laboratory of the Department of Physiology, Xinxiang Medical College from June to October in 2005. ① Rats in the experimental group were intraperitoneally injected with ethanol (2.5 g/kg) which was dissolved in normal saline (20%). The loss of righting reflex and ataxia within 5 minutes indicated the successful model. Whereas rats in the control group were given saline of the same volume. ② Examinations of learning and memory ability: The Y-maze tests for learning and memory ability were performed at 6 hours after the models establishment. The rats were put into the Y-maze separately. The test was performed in a quiet and dark room. There was a lamp at the end of each of three pathways in Y-maze and the base of maze had electric net. All the lamps of the three pathways were turned on for 3 minutes and then turned off. One lamp was turned on randomly, and the other two delayed automatically. In 5 seconds

  7. TLR4, ATF-3 and IL8 inflammation mediator expression correlates with seizure frequency in human epileptic brain tissue.

    Science.gov (United States)

    Pernhorst, Katharina; Herms, Stefan; Hoffmann, Per; Cichon, Sven; Schulz, Herbert; Sander, Thomas; Schoch, Susanne; Becker, Albert J; Grote, Alexander

    2013-10-01

    Data from animal models has nicely shown that inflammatory processes in the central nervous system (CNS) can modulate seizure frequency. However, a potential relationship between the modulation of seizure frequency and gene expression of key inflammatory factors in human epileptic tissue is still unresolved. Brain tissue from pharmacoresistant patients with mesial temporal lobe epilepsy (mTLE) provides a unique prerequisite for clinico-neuropathological correlations. Here, we have concentrated on gene expression of the human key inflammatory mediators, TLR4, ATF-3 and IL8, in correlation to seizure frequency and additional clinical parameters in human epileptic brain tissue of pharmacoresistant mTLE patients. Furthermore, we characterized the cell types expressing the respective proteins in epileptic hippocampi. Total RNAs were isolated from n=26 hippocampi of pharmacoresistant mTLE patients using AllPrep DNA/RNA Mini Kit. cRNA was used for hybridization on Human HT-12 v3 Expression BeadChips with Illumina Direct Hybridization Assay Kit and resulting gene expression data was normalized based on the Illumina BeadStudio software suite by means of quantile normalization with background subtraction. Corresponding human hippocampal sections for immunohistochemistry were probed with antibodies against TLR4, ATF-3, IL8 and glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN) and the microglial marker HLA-DR. We observed abundant TLR4 gene expression to relate to seizure frequency per month. For ATF-3, we found an inverse correlation of expression to seizure frequency. Lower expression of IL8 was significantly associated with high seizure frequency. Further, we detected TLR4 expression in neurons and GFAP-positive astrocytes of pharmacoresistant mTLE patients. Only neurons of human epileptic hippocampi express ATF-3. IL8 was expressed in microglia and reactive astrocytes. Our results suggest a differential correlation of key inflammatory factor

  8. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn infant

  9. Gestational age dependent changes of the fetal brain, liver and adipose tissue fatty acid compositions in a population with high fish intakes

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Offringa, Pieter J.; Boersma, E. Rudy; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    2012-01-01

    Introduction: There are no data on the intrauterine fatty acid (FA) compositions of brain, liver and adipose tissue of infants born to women with high fish intakes. Subjects and methods: We analyzed the brain (n = 18), liver (n = 14) and adipose tissue (n = 11) FA compositions of 20 stillborn

  10. Quantification of Neurotransmitters in Mouse Brain Tissue by Using Liquid Chromatography Coupled Electrospray Tandem Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available A simple and rapid liquid chromatography tandem mass spectrometry method has been developed for the determination of BH4, DA, 5-HT, NE, EP, Glu, and GABA in mouse brain using epsilon-acetamidocaproic acid and isotopically labeled neurotransmitters as internal standards. Proteins in the samples were precipitated by adding acetonitrile, and then the supernatants were separated by a Sepax Polar-Imidazole (2.1 mm × 100 mm, i.d., 3 μm column by adding a mixture of 10 mM ammonium formate in acetonitrile/water (75 : 25, v/v, 300 μl/min for BH4 and DA. To assay 5-HT, NE, EP, Glu, and GABA; a Luna 3 μ C18 (3.0 mm × 150 mm, i.d., 3 μm column was used by adding a mixture of 1% formic acid in acetonitrile/water (20 : 80, v/v, 350 μl/min. The total chromatographic run time was 5.5 min. The method was validated for the analysis of samples. The calibration curve was linear between 10 and 2000 ng/g for BH4 r2=0.995, 10 and 5000 ng/g for DA r2=0.997, 20 and 10000 ng/g for 5-HT r2=0.994, NE r2=0.993, and EP r2=0.993, and 0.2 and 200 μg/g for Glu r2=0.996 and GABA r2=0.999 in the mouse brain tissues. As stated above, LC-MS/MS results were obtained and established to be a useful tool for the quantitative analysis of BH4, DA, 5-HT, NE, EP, Glu, and GABA in the experimental rodent brain.

  11. Semi-automated image processing system for micro- to macro-scale analysis of immunohistopathology: application to ischemic brain tissue.

    Science.gov (United States)

    Wu, Chunyan; Zhao, Weizhao; Lin, Baowan; Ginsberg, Myron D

    2005-04-01

    Immunochemical staining techniques are commonly used to assess neuronal, astrocytic and microglial alterations in experimental neuroscience research, and in particular, are applied to tissues from animals subjected to ischemic stroke. Immunoreactivity of brain sections can be measured from digitized immunohistology slides so that quantitative assessment can be carried out by computer-assisted analysis. Conventional methods of analyzing immunohistology are based on image classification techniques applied to a specific anatomic location at high magnification. Such micro-scale localized image analysis limits one for further correlative studies with other imaging modalities on whole brain sections, which are of particular interest in experimental stroke research. This report presents a semi-automated image analysis method that performs convolution-based image classification on micro-scale images, extracts numerical data representing positive immunoreactivity from the processed micro-scale images and creates a corresponding quantitative macro-scale image. The present method utilizes several image-processing techniques to cope with variances in intensity distribution, as well as artifacts caused by light scattering or heterogeneity of antigen expression, which are commonly encountered in immunohistology. Micro-scale images are composed by a tiling function in a mosaic manner. Image classification is accomplished by the K-means clustering method at the relatively low-magnification micro-scale level in order to increase computation efficiency. The quantitative macro-scale image is suitable for correlative analysis with other imaging modalities. This method was applied to different immunostaining antibodies, such as endothelial barrier antigen (EBA), lectin, and glial fibrillary acidic protein (GFAP), on histology slides from animals subjected to middle cerebral artery occlusion by the intraluminal suture method. Reliability tests show that the results obtained from

  12. Brain tissue oxygen tension and its response to physiological manipulations: influence of distance from injury site in a swine model of traumatic brain injury.

    Science.gov (United States)

    Hawryluk, Gregory W J; Phan, Nicolas; Ferguson, Adam R; Morabito, Diane; Derugin, Nikita; Stewart, Campbell L; Knudson, M Margaret; Manley, Geoffrey; Rosenthal, Guy

    2016-11-01

    OBJECTIVE The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites. METHODS A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation. RESULTS Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively. CONCLUSIONS PbtO2 measurements are strongly influenced by the distance from the

  13. Image-based metrology of porous tissue engineering scaffolds

    Science.gov (United States)

    Rajagopalan, Srinivasan; Robb, Richard A.

    2006-03-01

    Tissue engineering is an interdisciplinary effort aimed at the repair and regeneration of biological tissues through the application and control of cells, porous scaffolds and growth factors. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural indices that can be derived quantitatively from the microCT and microMR images of the scaffolds. However, the randomness of pore-solid distributions in conventional stochastic scaffolds presents unique computational challenges. As a result, image-based characterization of scaffolds has been predominantly qualitative. In this paper, we discuss quantitative image-based techniques that can be used to compute the metrological indices of porous tissue engineering scaffolds. While bulk averaged quantities such as porosity and surface are derived directly from the optimal pore-solid delineations, the spatially distributed geometric indices are derived from the medial axis representations of the pore network. The computational framework proposed (to the best of our knowledge for the first time in tissue engineering) in this paper might have profound implications towards unraveling the symbiotic structure-function relationship of porous tissue engineering scaffolds.

  14. The association between brain natriuretic peptide and tissue Doppler parameters in children with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Taliha Öner

    2016-01-01

    Full Text Available In this study, we investigated the association between brain natriuretic peptide (BNP levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM. We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17, 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19 and BNP in the patients. The patients were divided into two groups according to the presence (Group 1 or absence (Group 2 of left ventricular (LV outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

  15. Review: Polymeric-Based 3D Printing for Tissue Engineering.

    Science.gov (United States)

    Wu, Geng-Hsi; Hsu, Shan-Hui

    Three-dimensional (3D) printing, also referred to as additive manufacturing, is a technology that allows for customized fabrication through computer-aided design. 3D printing has many advantages in the fabrication of tissue engineering scaffolds, including fast fabrication, high precision, and customized production. Suitable scaffolds can be designed and custom-made based on medical images such as those obtained from computed tomography. Many 3D printing methods have been employed for tissue engineering. There are advantages and limitations for each method. Future areas of interest and progress are the development of new 3D printing platforms, scaffold design software, and materials for tissue engineering applications.

  16. Tissomics: two- and three-dimensional distribution of nuclei in brain tissue using laser scanning cytometry (LSC)

    Science.gov (United States)

    Lenz, Domnik; Mittag, Anja; Mosch, Birgit; Bocsi, Jozsef; Arendt, Thomas; Tarnok, Attila

    2005-03-01

    Automated quantitative (i.e. stochiometric) analysis of tissues is of eminent importance in the understanding of all interactions between cells in their natural environment. In tissue cytometry a solid trigger is necessary in order to unequivocally differentiate between cellular and non-cellular events. This can be best performed by nuclear staining. Aim of this study was to analyze a brain tissue section by laser scanning cytometry (LSC) in order to depict the threedimensional distribution of nuclei in the tissue. To this end the section was measured in several foci and different nuclei detected in several depths of the tissue were assigned to the respective layer. Frozen sections of formalin-fixed rat or human brain tissue (120μm thickness) were incubated with propidiumiodide (PI) (50μg/ml) and covered on slides. For analysis by the LSC propidiumiodide was used as trigger. After a first analysis focussed on the top of the tissue, the focus was adjusted in 30μm steps deeper into the tissue. Per analysis data of at least 50,000 cells were acquired. After finishing measurements from all depths of the field were merged, i.e. data were combined into a composite data file. With the special features of the LSC it was possible to develop a method depicting the threedimensional distribution of the nuclei in solid tissue sections. LSC can be useful tool for this relatively new field of solid tissue cytometry termed tissomics. After evaluation of methods like this, so far not available data can be analysed for diagnostic purposes. By these studies we intend to demonstrate the power of the LSC for the routine pathological use. This should add up to the bright versatility of applications for the LSC as a cytometric instrument suitable for high throughput and high content analysis.

  17. A novel absolute quantitative imaging strategy of iron, copper and zinc in brain tissues by Isotope Dilution Laser Ablation ICP-MS.

    Science.gov (United States)

    Feng, Liuxing; Wang, Jun; Li, Hongmei; Luo, Xinzheng; Li, Jiao

    2017-09-01

    Isotope Dilution Laser Ablation ICP-MS (ID-LA-ICP-MS), because of its impressive spatial resolution capacity and precise means for quantification, is one of the most promising tools for in-situ quantitative imaging of trace elements in biological samples. In the ID-LA-ICP-MS strategy for tissue section, the tissue must be maintained intact during the whole sample preparation process. Therefore, how to homogeneously distribute enriched isotope spike on tissue section and how to confirm isotope equilibration between sample and spike are two important challenges. In this study, we reported a novel quantitative imaging strategy for biological thin section based on ID-LA-ICP-MS. To distribute the enriched isotope spikes on tissue section homogeneously, a "border" was constructed to make spike droplet stay on the tissue for isotope exchange. Laser ablation and isotope exchange parameters were also investigated to obtain optimal ID-LA-ICP-MS conditions. The prepared homogeneous in-house standard was used to validate the ID-LA-ICP-MS approach and good agreement with the bulk analysis was achieved. On this basis, quantitative imaging of Fe, Cu and Zn in real mouse brain of Alzheimer's Disease (AD) were measured by the improved methodology. Assessment of the method for real sample was undertaken by comparison of the LA-ICP-MS data with that obtained by micro-XRF. Moreover, comparative analysis of elements distribution and immunohistochemical markers in AD mouse brain was also carried out. The similar distributional patterns demonstrated that the proposed methodology is potential to investigate the correlation of biomarker heterogeneity and elements distribution, and may be useful to understand such complex brain mechanisms in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Immunohistochemistry for the detection of neural and inflammatory cells in equine brain tissue

    Directory of Open Access Journals (Sweden)

    Gretchen H. Delcambre

    2016-01-01

    Full Text Available Phenotypic characterization of cellular responses in equine infectious encephalitides has had limited description of both peripheral and resident cell populations in central nervous system (CNS tissues due to limited species-specific reagents that react with formalin-fixed, paraffin embedded tissue (FFPE. This study identified a set of antibodies for investigating the immunopathology of infectious CNS diseases in horses. Multiple commercially available staining reagents and antibodies derived from antigens of various species for manual immunohistochemistry (IHC were screened. Several techniques and reagents for heat-induced antigen retrieval, non-specific protein blocking, endogenous peroxidase blocking, and visualization-detection systems were tested during IHC protocol development. Boiling of slides in a low pH, citrate-based buffer solution in a double-boiler system was most consistent for epitope retrieval. Pressure-cooking, microwaving, high pH buffers, and proteinase K solutions often resulted in tissue disruption or no reactivity. Optimal blocking reagents and concentrations of each working antibody were determined. Ultimately, a set of monoclonal (mAb and polyclonal antibodies (pAb were identified for CD3+ (pAb A0452, Dako T-lymphocytes, CD79αcy+ B-lymphocytes (mAb HM57, Dako, macrophages (mAb MAC387, Leica, NF-H+ neurons (mAb NAP4, EnCor Biotechnology, microglia/macrophage (pAb Iba-1, Wako, and GFAP+ astrocytes (mAb 5C10, EnCor Biotechnology. In paraffin embedded tissues, mAbs and pAbs derived from human and swine antigens were very successful at binding equine tissue targets. Individual, optimized protocols are provided for each positively reactive antibody for analyzing equine neuroinflammatory disease histopathology.

  19. Immunohistochemistry for the detection of neural and inflammatory cells in equine brain tissue.

    Science.gov (United States)

    Delcambre, Gretchen H; Liu, Junjie; Herrington, Jenna M; Vallario, Kelsey; Long, Maureen T

    2016-01-01

    Phenotypic characterization of cellular responses in equine infectious encephalitides has had limited description of both peripheral and resident cell populations in central nervous system (CNS) tissues due to limited species-specific reagents that react with formalin-fixed, paraffin embedded tissue (FFPE). This study identified a set of antibodies for investigating the immunopathology of infectious CNS diseases in horses. Multiple commercially available staining reagents and antibodies derived from antigens of various species for manual immunohistochemistry (IHC) were screened. Several techniques and reagents for heat-induced antigen retrieval, non-specific protein blocking, endogenous peroxidase blocking, and visualization-detection systems were tested during IHC protocol development. Boiling of slides in a low pH, citrate-based buffer solution in a double-boiler system was most consistent for epitope retrieval. Pressure-cooking, microwaving, high pH buffers, and proteinase K solutions often resulted in tissue disruption or no reactivity. Optimal blocking reagents and concentrations of each working antibody were determined. Ultimately, a set of monoclonal (mAb) and polyclonal antibodies (pAb) were identified for CD3(+) (pAb A0452, Dako) T-lymphocytes, CD79αcy(+) B-lymphocytes (mAb HM57, Dako), macrophages (mAb MAC387, Leica), NF-H(+) neurons (mAb NAP4, EnCor Biotechnology), microglia/macrophage (pAb Iba-1, Wako), and GFAP(+) astrocytes (mAb 5C10, EnCor Biotechnology). In paraffin embedded tissues, mAbs and pAbs derived from human and swine antigens were very successful at binding equine tissue targets. Individual, optimized protocols are provided for each positively reactive antibody for analyzing equine neuroinflammatory disease histopathology.

  20. Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue - Differentiating between postmortem formation and antemortem intake.

    Science.gov (United States)

    Thomsen, Ragnar; Rasmussen, Brian Schou; Johansen, Sys Stybe; Linnet, Kristian

    2017-03-01

    Gamma-hydroxybutyrate (GHB) is a recreational drug, a drug of abuse, as well as an endogenous molecule in mammals. The drug has become infamous as a tool for drug-facilitated sexual assault. GHB is found in low concentrations in living humans, while at postmortem the concentration of GHB rises due to fermentation processes. The endogenous nature of GHB leads to difficulty in interpretation of concentrations, as the source of GHB is not obvious. Postmortem brain and blood samples were collected from 221 individuals at autopsy. Of these, 218 were not suspected of having ingested GHB, while GHB intake was reported for the last three (cases A-C). Decomposition level was estimated and cases classified into no/minor and advanced decomposition. Brain samples were extracted from the frontal lobe; only gray matter from the cerebral cortex was used. Blood was drawn from the femoral vein. Brain samples were homogenized and diluted with water. Brain homogenates or femoral blood were then prepared using protein precipitation and GHB was quantified with UHPLC-MS/MS. For 189 cases where ingestion of GHB was not suspected and where no/minor decomposition had occurred the concentrations were in the range 4.8-45.4mg/kg (median 15.3mg/kg) in blood and not-detected to 9.8mg/kg (median 4.8mg/kg) in brain tissue. For case A, where intoxication with GHB was deemed to be the sole cause of death, the concentrations were 199 and 166mg/kg in blood and brain, respectively. For case B, where intoxication with GHB was a contributing factor of death, the respective concentrations were 142 and 78.4mg/kg. For case C, where GHB was ingested but the cause of death was opioid poisoning, the concentrations were 40.3 and 12.7mg/kg. The results demonstrate that postmortem-formed levels of GHB are much lower in brain than peripheral blood. Analysis of GHB in brain tissue thus provides for an improved capability to identify an exogenous source of GHB. By measuring GHB in brain tissue and employing a cut

  1. Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

    2014-06-01

    Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

  2. Focussed ion beam milling and scanning electron microscopy of brain tissue.

    Science.gov (United States)

    Knott, Graham; Rosset, Stéphanie; Cantoni, Marco

    2011-07-06

    This protocol describes how biological samples, like brain tissue, can be imaged in three dimensions using the focussed ion beam/scanning electron microscope (FIB/SEM). The samples are fixed with aldehydes, heavy metal stained using osmium tetroxide and uranyl acetate. They are then dehydrated with alcohol and infiltrated with resin, which is then hardened. Using a light microscope and ultramicrotome with glass knives, a small block containing the region interest close to the surface is made. The block is then placed inside the FIB/SEM, and the ion beam used to roughly mill a vertical face along one side of the block, close to this region. Using backscattered electrons to image the underlying structures, a smaller face is then milled with a finer ion beam and the surface scrutinised more closely to determine the exact area of the face to be imaged and milled. The parameters of the microscope are then set so that the face is repeatedly milled and imaged so that serial images are collected through a volume of the block. The image stack will typically contain isotropic voxels with dimenions as small a 4 nm in each direction. This image quality in any imaging plane enables the user to analyse cell ultrastructure at any viewing angle within the image stack.

  3. Zinc-triggered induction of tissue plasminogen activator by brain-derived neurotrophic factor and metalloproteinases.

    Science.gov (United States)

    Hwang, Ih-Yeon; Sun, Eun-Sun; An, Ji Hak; Im, Hana; Lee, Sun-Ho; Lee, Joo-Yong; Han, Pyung-Lim; Koh, Jae-Young; Kim, Yang-Hee

    2011-09-01

    Tissue plasminogen activator (tPA) is necessary for hippocampal long-term potentiation. Synaptically released zinc also contributes to long-term potentiation, especially in the hippocampal CA3 region. Using cortical cultures, we examined whether zinc increased the concentration and/or activity of tPA. Two hours after a 10-min exposure to 300 μM zinc, expression of tPA and its substrate, plasminogen, were significantly increased, as was the proteolytic activity of tPA. In contrast, increasing extracellular or intracellular calcium levels did not affect the expression or secretion of tPA. Changing zinc influx or chelating intracellular zinc also failed to alter tPA/plasminogen induction by zinc, indicating that zinc acts extracellularly. Zinc-mediated extracellular activation of matrix metalloproteinase (MMP) underlies the up-regulation of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (Trk) signaling. Consistent with these findings, co-treatment with a neutralizing antibody against BDNF or specific inhibitors of MMPs or Trk largely reversed tPA/plasminogen induction by zinc. Treatment of cortical cultures with p-aminophenylmercuric acetate, an MMP activator, MMP-2, or BDNF alone induced tPA/plasminogen expression. BDNF mRNA and protein expression was also increased by zinc and mediated by MMPs. Thus, an extracellular zinc-dependent, MMP- and BDNF-mediated synaptic mechanism may regulate the levels and activity of tPA.

  4. Modulation of lipid peroxidation, hypolipidemic and antioxidant activities in brain tissues of diabetic rats by fibre - Enriched biscuits

    Institute of Scientific and Technical Information of China (English)

    Ochuko L Erukainure; Folasade O Adeboyejo; Gloria N Elemo; Osaretin AT Ebuehi

    2012-01-01

    Objective: To investigate the effect of feeding fibre - enriched biscuit on the antioxidant and hypolipidemic activities in brain tissues of diabetic rats. Method: Diabetes was induced by a single intraperitoneal injection of alloxan. Treatment lasted for 14 d, after which the rats were sacrificed by cervical dislocation. Brain tissues were used for the assessment of GSH, catalase, SOD and lipid peroxidation as well as lipid profiles. Result: Induction of diabetes led to a significant decrease in GSH level, elevated SOD and catalase activities. These were significantly modified by the biscuits. There was an elevated level of malondialdehyde in the brain tissues of the untreated diabetic rats; this was significantly reduced by the biscuits. There was a significant decrease in HDL and a significant increase in LDL levels, total cholesterol and triglycerides in the untreated (diabetic) rats. Feeding with fibre - enriched biscuits led to decrease in the levels of total cholesterol, triglyceride, LDL - cholesterol and caused a significant increase in the levels of HDL. Conclusions: These results suggest a therapeutic and protective effect of the fibre -enriched biscuits against diabetic - induced brain toxicity in rats.

  5. Hemispheric asymmetry of electroencephalography-based functional brain networks.

    Science.gov (United States)

    Jalili, Mahdi

    2014-11-12

    Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

  6. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python

    Directory of Open Access Journals (Sweden)

    Nicolas eRey-Villamizar

    2014-04-01

    Full Text Available In this article, we describe use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis task, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral brain tissue images surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels, 6,000$times$10,000$times$500 voxels with 16 bits/voxel, implying image sizes exceeding 250GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analytics for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment consisting. Our Python script enables efficient data storage and movement between compute and storage servers, logging all processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

  7. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python.

    Science.gov (United States)

    Rey-Villamizar, Nicolas; Somasundar, Vinay; Megjhani, Murad; Xu, Yan; Lu, Yanbin; Padmanabhan, Raghav; Trett, Kristen; Shain, William; Roysam, Badri

    2014-01-01

    In this article, we describe the use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes, including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis tasks, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral images of brain tissue surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels. Each channel consists of 6000 × 10,000 × 500 voxels with 16 bits/voxel, implying image sizes exceeding 250 GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analysis for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN) capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment. Our Python script enables efficient data storage and movement between computers and storage servers, logs all the processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

  8. Multimodal Raman-fluorescence spectroscopy of formalin fixed samples is able to discriminate brain tumors from dysplastic tissue

    Science.gov (United States)

    Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Buccoliero, Anna Maria; Pavone, Francesco Saverio

    2014-05-01

    In the recent years, there has been a considerable surge in the application of spectroscopy for disease diagnosis. Raman and fluorescence spectra provide characteristic spectral profile related to biochemical and morphological changes when tissues progress from normal state towards malignancy. Spectroscopic techniques offer the advantage of being minimally invasive compared to traditional histopathology, real time and quantitative. In biomedical optical diagnostics, freshly excised specimens are preferred for making ex-vivo spectroscopic measurements. With regard to fresh tissues, if the lab is located far away from the clinic it could pose a problem as spectral measurements have to be performed immediately after dissection. Tissue samples are usually placed in a fixative agent such as 4% formaldehyde to preserve the samples before processing them for routine histopathological studies. Fixation prevents the tissues from decomposition by arresting autolysis. In the present study, we intend to investigate the possibility of using formalin fixed samples for discrimination of brain tumours from dysplastic tissue using Raman and fluorescence spectroscopy. Formalin fixed samples were washed with phosphate buffered saline for about 5 minutes in order to remove the effects of formalin during spectroscopic measurements. In case of fluorescence spectroscopy, changes in spectral profile have been observed in the region between 550-670 nm between dysplastic and tumor samples. For Raman measurements, we found significant differences in the spectral profiles between dysplasia and tumor. In conclusion, formalin fixed samples can be potentially used for the spectroscopic discrimination of tumor against dysplastic tissue in brain samples.

  9. Streamlined bioreactor-based production of human cartilage tissues.

    Science.gov (United States)

    Tonnarelli, B; Santoro, R; Adelaide Asnaghi, M; Wendt, D

    2016-05-27

    Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.

  10. A Hybrid DE-RGSO-ELM for Brain Tumor Tissue Categorization in 3D Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    K. Kothavari

    2014-01-01

    Full Text Available Medical diagnostics, a technique used for visualizing the internal structures and functions of human body, serves as a scientific tool to assist physicians and involves direct use of digital imaging system analysis. In this scenario, identification of brain tumors is complex in the diagnostic process. Magnetic resonance imaging (MRI technique is noted to best assist tissue contrast for anatomical details and also carries out mechanisms for investigating the brain by functional imaging in tumor predictions. Considering 3D MRI model, analyzing the anatomy features and tissue characteristics of brain tumor is complex in nature. Henceforth, in this work, feature extraction is carried out by computing 3D gray-level cooccurence matrix (3D GLCM and run-length matrix (RLM and feature subselection for dimensionality reduction is performed with basic differential evolution (DE algorithm. Classification is performed using proposed extreme learning machine (ELM, with refined group search optimizer (RGSO technique, to select the best parameters for better simplification and training of the classifier for brain tissue and tumor characterization as white matter (WM, gray matter (GM, cerebrospinal fluid (CSF, and tumor. Extreme learning machine outperforms the standard binary linear SVM and BPN for medical image classifier and proves better in classifying healthy and tumor tissues. The comparison between the algorithms proves that the mean and standard deviation produced by volumetric feature extraction analysis are higher than the other approaches. The proposed work is designed for pathological brain tumor classification and for 3D MRI tumor image segmentation. The proposed approaches are applied for real time datasets and benchmark datasets taken from dataset repositories.

  11. The quantitative analysis of S100 in the brain tissue and serum following diffuse brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Wang Qi; Huang Ping; Xing Bo; Tuo Ya; Zhang Yongpan; Tian Weiping; Wang Zhenyuan

    2007-01-01

    Objective To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0.5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.

  12. The molecular bases of the suicidal brain

    Science.gov (United States)

    Turecki, Gustavo

    2017-01-01

    Suicide ranks among the leading causes of death around the world, and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors associate with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes associated with suicidality, and presents some promising avenues for future research. PMID:25354482

  13. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

    OpenAIRE

    Davey, P G; Charter, M; Kelly, S; Varma, T R; Jacobson, I.; A. Freeman; Precious, E; Lambert, J

    1994-01-01

    Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken f...

  14. Constraint-based soft tissue simulation for virtual surgical training.

    Science.gov (United States)

    Tang, Wen; Wan, Tao Ruan

    2014-11-01

    Most of surgical simulators employ a linear elastic model to simulate soft tissue material properties due to its computational efficiency and the simplicity. However, soft tissues often have elaborate nonlinear material characteristics. Most prominently, soft tissues are soft and compliant to small strains, but after initial deformations they are very resistant to further deformations even under large forces. Such material characteristic is referred as the nonlinear material incompliant which is computationally expensive and numerically difficult to simulate. This paper presents a constraint-based finite-element algorithm to simulate the nonlinear incompliant tissue materials efficiently for interactive simulation applications such as virtual surgery. Firstly, the proposed algorithm models the material stiffness behavior of soft tissues with a set of 3-D strain limit constraints on deformation strain tensors. By enforcing a large number of geometric constraints to achieve the material stiffness, the algorithm reduces the task of solving stiff equations of motion with a general numerical solver to iteratively resolving a set of constraints with a nonlinear Gauss-Seidel iterative process. Secondly, as a Gauss-Seidel method processes constraints individually, in order to speed up the global convergence of the large constrained system, a multiresolution hierarchy structure is also used to accelerate the computation significantly, making interactive simulations possible at a high level of details. Finally, this paper also presents a simple-to-build data acquisition system to validate simulation results with ex vivo tissue measurements. An interactive virtual reality-based simulation system is also demonstrated.

  15. An MRI-based atlas and database of the developing mouse brain.

    Science.gov (United States)

    Chuang, Nelson; Mori, Susumu; Yamamoto, Akira; Jiang, Hangyi; Ye, Xin; Xu, Xin; Richards, Linda J; Nathans, Jeremy; Miller, Michael I; Toga, Arthur W; Sidman, Richard L; Zhang, Jiangyang

    2011-01-01

    The advent of mammalian gene engineering and genetically modified mouse models has led to renewed interest in developing resources for referencing and quantitative analysis of mouse brain anatomy. In this study, we used diffusion tensor imaging (DTI) for quantitative characterization of anatomical phenotypes in the developing mouse brain. As an anatomical reference for neuroscience research using mouse models, this paper presents DTI based atlases of ex vivo C57BL/6 mouse brains at several developmental stages. The atlas complements existing histology and MRI-based atlases by providing users access to three-dimensional, high-resolution images of the developing mouse brain, with distinct tissue contrasts and segmentations of major gray matter and white matter structures. The usefulness of the atlas and database was demonstrated by quantitative measurements of the development of major gray matter and white matter structures. Population average images of the mouse brain at several postnatal stages were created using large deformation diffeomorphic metric mapping and their anatomical variations were quantitatively characterized. The atlas and database enhance our ability to examine the neuroanatomy in normal or genetically engineered mouse strains and mouse models of neurological diseases.

  16. An MRI-based Atlas and Database of the Developing Mouse Brain

    Science.gov (United States)

    Chuang, Nelson; Mori, Susumu; Yamamoto, Akira; Jiang, Hangyi; Ye, Xin; Xu, Xin; Richards, Linda J.; Nathans, Jeremy; Miller, Michael I.; W.Toga, Arthur; Sidman, Richard L.; Zhang, Jiangyang

    2010-01-01

    The advent of mammalian gene engineering and genetically modified mouse models has led to renewed interest in developing resources for referencing and quantitative analysis of mouse brain anatomy. In this study, we used diffusion tensor imaging (DTI) for quantitative characterization of anatomical phenotypes in the developing mouse brain. As an anatomical reference for neuroscience research using mouse models, this paper presents DTI based atlases of ex vivo C57BL/6 mouse brains at several developmental stages. The atlas complements existing histology and MRI-based atlases by providing users access to three-dimensional, high-resolution images of the developing mouse brain, with distinct tissue contrasts and segmentations of major gray matter and white matter structures. The usefulness of the atlas and database was demonstrated by quantitative measurements of the development of major gray matter and white matter structures. Population average images of the mouse brain at several postnatal stages were created using large deformation diffeomorphic metric mapping and their anatomical variations were quantitatively characterized. The atlas and database enhance our ability to examine the neuroanatomy in normal or genetically engineered mouse strains and mouse models of neurological diseases. PMID:20656042

  17. Olfactory Mucosa Tissue Based Biosensor for Bioelectronic Nose

    Science.gov (United States)

    Liu, Qingjun; Ye, Weiwei; Yu, Hui; Hu, Ning; Cai, Hua; Wang, Ping

    2009-05-01

    Biological olfactory system can distinguish thousands of odors. In order to realize the biomimetic design of electronic nose on the principle of mammalian olfactory system, we have reported bioelectronic nose based on cultured olfactory cells. In this study, the electrical property of the tissue-semiconductor interface was analyzed by the volume conductor theory and the sheet conductor model. Olfactory mucosa tissue of rat was isolated and fixed on the surface of the light-addressable potentiometric sensor (LAPS), with the natural stations of the neuronal populations and functional receptor unit of the cilia well reserved. By the extracellular potentials of the olfactory receptor cells of the mucosa tissue monitored, both the simulation and the experimental results suggested that this tissue-semiconductor hybrid system was sensitive to odorants stimulation.

  18. Powder-based 3D printing for bone tissue engineering.

    Science.gov (United States)

    Brunello, G; Sivolella, S; Meneghello, R; Ferroni, L; Gardin, C; Piattelli, A; Zavan, B; Bressan, E

    2016-01-01

    Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Hard X-ray submicrometer tomography of human brain tissue at Diamond Light Source

    Science.gov (United States)

    Khimchenko, A.; Bikis, C.; Schulz, G.; Zdora, M.-C.; Zanette, I.; Vila-Comamala, J.; Schweighauser, G.; Hench, J.; Hieber, S. E.; Deyhle, H.; Thalmann, P.; Müller, B.

    2017-06-01

    There is a lack of the necessary methodology for three-dimensional (3D) investigation of soft tissues with cellular resolution without staining or tissue transformation. Synchrotron radiation based hard X-ray in-line phase contrast tomography using single-distance phase reconstruction (SDPR) provides high spatial resolution and density contrast for the visualization of individual cells using a standard specimen preparation and data reconstruction. In this study, we demonstrate the 3D characterization of a formalin-fixed paraffin-embedded (FFPE) human cerebellum specimen by SDPR at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, UK) at pixel sizes down to 0.45 μm. The approach enables visualization of cerebellar layers (Stratum moleculare and Stratum granulosum), the 3D characterization of individual cells (Purkinje, stellate and granule cells) and can even resolve some subcellular structures (nucleus and nucleolus of Purkinje cells). The tomographic results are qualitatively compared to hematoxylin and eosin (H&E) stained histological sections. We demonstrate the potential benefits of hard X-ray microtomography for the investigations of biological tissues in comparison to conventional histology.

  20. Web based brain volume calculation for magnetic resonance images.

    Science.gov (United States)

    Karsch, Kevin; Grinstead, Brian; He, Qing; Duan, Ye

    2008-01-01

    Brain volume calculations are crucial in modern medical research, especially in the study of neurodevelopmental disorders. In this paper, we present an algorithm for calculating two classifications of brain volume, total brain volume (TBV) and intracranial volume (ICV). Our algorithm takes MRI data as input, performs several preprocessing and intermediate steps, and then returns each of the two calculated volumes. To simplify this process and make our algorithm publicly accessible to anyone, we have created a web-based interface that allows users to upload their own MRI data and calculate the TBV and ICV for the given data. This interface provides a simple and efficient method for calculating these two classifications of brain volume, and it also removes the need for the user to download or install any applications.

  1. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    Science.gov (United States)

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  2. Cell and brain tissue imaging of the flavonoid fisetin using label-free two-photon microscopy.

    Science.gov (United States)

    Krasieva, Tatiana B; Ehren, Jennifer; O'Sullivan, Thomas; Tromberg, Bruce J; Maher, Pamela

    2015-10-01

    Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglia and astrocytes and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. However, key questions about its targets and brain penetration remain. In this study, we used label-free two-photon microscopy of intrinsic fisetin fluorescence to examine the localization of fisetin in living nerve cells and the brains of living mice. In cells, fisetin but not structurally related flavonols with different numbers of hydroxyl groups, localized to the nucleoli suggesting that key targets of fisetin may reside in this organelle. In the mouse brain, following intraperitoneal injection and oral administration, fisetin rapidly distributed to the blood vessels of the brain followed by a slower dispersion into the brain parenchyma. Thus, these results provide further support for the effects of fisetin on brain function. In addition, they suggest that label-free two-photon microscopy may prove useful for studying the intracellular and tissue distribution of other intrinsically-fluorescent flavonoids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Covalent binding of formalin fixed paraffin embedded brain tissue sections to glass slides suitable for in situ hybridization.

    Science.gov (United States)

    Tourtellotte, W W; Verity, A N; Schmid, P; Martinez, S; Shapshak, P

    1987-02-01

    A novel method for covalently binding formalin fixed paraffin embedded (FFPE) tissue sections to glass microscope slides is validated suitable for in situ hybridization (ISH). Using the organosilane methodology of Maples (1985), 100% tissue adhesion is reported with no nonspecific probe binding, staining, or autoradiographic artefacts. JC viral nucleic acid sequences are successfully detected in FFPE progressive multifocal leukoencephalopathy brain tissue and the Tm of the hybridized product is estimated. From the Tm the most stringent washing condition resulting in an optimal signal to noise ratio is determined. A comparison is made between currently used methods of tissue adhesion and the proposed organosilane methodology. This methodology greatly facilitates studies of conditions for ISH and elucidation of mechanisms of viral infections requiring consecutive FFPE sections. It is also applicable to studies using cryosections and cultured cells.

  4. Technical pitfalls in a porcine brain retraction model. The impact of brain spatula on the retracted brain tissue in a porcine model: a feasibility study and its technical pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Thiex, R.; Hans, F.J.; Gilsbach, J.M. [Aachen University, Department of Neurosurgery, Aachen (Germany); Krings, T. [Aachen University, Department of Neuroradiology, Aachen (Germany); Sellhaus, B. [Aachen University, Department of Neuropathology, Aachen (Germany)

    2005-10-01

    We describe technical pitfalls of a porcine brain injury model for identifying primary and secondary pathological sequelae following brain retraction by brain spatula. In 16 anaesthetised male pigs, the right frontal brain was retracted in the interhemispheric fissure by a brain spatulum with varying pressures applied by the gravitational force of weights from 10 to 70 g for a duration of 30 min. The retracted brain tissue was monitored for changes in intracranial pressure and perfusion of the cortex using a Laser Doppler Perfusion Imager (MoorLDI). To evaluate the extent of oedema and cortical contusions, MRI was performed 30 min and 72 h after brain retraction. Following the MR scan, the retracted brain areas were histopathologically assessed using H and E and Fluoro-Jade B staining for neuronal damage. Sinus occlusion occurred in four animals, resulting in bilateral cortical contusions and extensive brain oedema. Retracting the brain with weights of 70 g (n=4) caused extensive oedema on FLAIR images that correlated clinically with a hemiparesis in three animals. Morphologically, an increased number of Fluoro-Jade B-positive neurons were found. A sequential decrease in weights prevented functional deficits in animals. A retraction pressure applied by 10-g weights (n=7) caused a mean rise in intracranial pressure to 4.0{+-}3.1 mm Hg, and a decrement in mean cortical perfusion from 740.8{+-}41.5 to 693.8{+-}72.4 PU/cm2, (P<0.24). A meticulous dissection of the interhemispheric fissure and a reduction of weights to 10 g were found to be mandatory to study the cortical impact caused by brain spatula reproducibly. (orig.)

  5. Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

    Science.gov (United States)

    Tice, Colin M; Noto, Paul B; Fan, Kristi Yi; Zhao, Wei; Lotesta, Stephen D; Dong, Chengguo; Marcus, Andrew P; Zheng, Ya-Jun; Chen, Guozhou; Wu, Zhongren; Van Orden, Rebecca; Zhou, Jing; Bukhtiyarov, Yuri; Zhao, Yi; Lipinski, Kerri; Howard, Lamont; Guo, Joan; Kandpal, Geeta; Meng, Shi; Hardy, Andrew; Krosky, Paula; Gregg, Richard E; Leftheris, Katerina; McKeever, Brian M; Singh, Suresh B; Lala, Deepak; McGeehan, Gerard M; Zhuang, Linghang; Claremon, David A

    2016-10-15

    Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected.

  6. Effects of electro-acupuncture on brain tissue norepinephrine contents in a morphine withdrawal anxiety mouse model

    Institute of Scientific and Technical Information of China (English)

    Qizhi Zhou; Yuxing Liu; Xuguang Liu; Jiaolu Wei; Yong Tang; Junmei Wu; Yi Pu

    2008-01-01

    BACKGROUND: Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE: This study was designed to observe the effects of electro-acupuncture, at the "Sanyinjiao" point (SP 6), on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal.DESIGN: A randomized controlled animal experiment. SETTING: This study was performed in the Laboratory of Acupuncture, Electro-acupuncture & Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001.MATERIALS: A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China (1985). Experimental reagents and equipment used were as follows: morphine hydrochloride (Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China), norepinephrine (Sigma Chemical Company, USA), fluorospectrophotometer (RF-510, Shimadzu Corporation, Japan), Han electro-acupuncture apparatus (WQ 1002, No. zun (91)-227270-588, Beijing Anlong Photoelectricity-Technique Company, China), and T-maze (self-made). METHODS: A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group: blank control, T-maze, model, model + electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal: the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were

  7. Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Aβ and insulin degradation

    Directory of Open Access Journals (Sweden)

    Castaño Eduardo M

    2008-12-01

    Full Text Available Abstract Background Insulin degrading enzyme (IDE is implicated in the regulation of amyloid β (Aβ steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's disease (AD. Although IDE sub-cellular localization has been well studied, the compartments relevant to Aβ degradation remain to be determined. Results Our results of live immunofluorescence, immuno gold electron-microscopy and gradient fractionation concurred to the demonstration that endogenous IDE from brain tissues and cell cultures is, in addition to its other localizations, a detergent-resistant membrane (DRM-associated metallopeptidase. Our pulse chase experiments were in accordance with the existence of two pools of IDE: the cytosolic one with a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated IDE co-localized with Aβ and its distribution (DRMs vs. non-DRMs and activity was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE was mis-located from DRMs by treating cells with methyl-β-cyclodextrin (MβCD, endogenous Aβ accumulated in the extracellular space and exogenous Aβ proteolysis was impaired. We detected a reduced amount of IDE in DRMs of membranes isolated from mice brain with endogenous reduced levels of cholesterol (Chol due to targeted deletion of one seladin-1 allele. We confirmed that a moderate shift of IDE from DRMs induced a substantial decrement on IDE-mediated insulin and Aβ degradation in vitro. Conclusion Our results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may act as platforms where Aβ accumulates, due to its hydrophobic properties, reaching local concentration close to its Km for IDE facilitating its clearance. Structural integrity of DRMs may also be required to tightly retain insulin receptor and IDE for

  8. Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Aβ and insulin degradation

    Science.gov (United States)

    Bulloj, Ayelén; Leal, María C; Surace, Ezequiel I; Zhang, Xue; Xu, Huaxi; Ledesma, Maria D; Castaño, Eduardo M; Morelli, Laura

    2008-01-01

    Background Insulin degrading enzyme (IDE) is implicated in the regulation of amyloid β (Aβ) steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's disease (AD). Although IDE sub-cellular localization has been well studied, the compartments relevant to Aβ degradation remain to be determined. Results Our results of live immunofluorescence, immuno gold electron-microscopy and gradient fractionation concurred to the demonstration that endogenous IDE from brain tissues and cell cultures is, in addition to its other localizations, a detergent-resistant membrane (DRM)-associated metallopeptidase. Our pulse chase experiments were in accordance with the existence of two pools of IDE: the cytosolic one with a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated IDE co-localized with Aβ and its distribution (DRMs vs. non-DRMs) and activity was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE was mis-located from DRMs by treating cells with methyl-β-cyclodextrin (MβCD), endogenous Aβ accumulated in the extracellular space and exogenous Aβ proteolysis was impaired. We detected a reduced amount of IDE in DRMs of membranes isolated from mice brain with endogenous reduced levels of cholesterol (Chol) due to targeted deletion of one seladin-1 allele. We confirmed that a moderate shift of IDE from DRMs induced a substantial decrement on IDE-mediated insulin and Aβ degradation in vitro. Conclusion Our results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may act as platforms where Aβ accumulates, due to its hydrophobic properties, reaching local concentration close to its Km for IDE facilitating its clearance. Structural integrity of DRMs may also be required to tightly retain insulin receptor and IDE for insulin proteolysis. The

  9. Collagen-Based Biomaterials for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    François Berthod

    2010-03-01

    Full Text Available Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.

  10. Gelatin-Based Materials in Ocular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    James B. Rose

    2014-04-01

    Full Text Available Gelatin has been used for many years in pharmaceutical formulation, cell culture and tissue engineering on account of its excellent biocompatibility, ease of processing and availability at low cost. Over the last decade gelatin has been extensively evaluated for numerous ocular applications serving as cell-sheet carriers, bio-adhesives and bio-artificial grafts. These different applications naturally have diverse physical, chemical and biological requirements and this has prompted research into the modification of gelatin and its derivatives. The crosslinking of gelatin alone or in combination with natural or synthetic biopolymers has produced a variety of scaffolds that could be suitable for ocular applications. This review focuses on methods to crosslink gelatin-based materials and how the resulting materials have been applied in ocular tissue engineering. Critical discussion of recent innovations in tissue engineering and regenerative medicine will highlight future opportunities for gelatin-based materials in ophthalmolog