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Sample records for subcortical white-matter lesions

  1. Automated localization of periventricular and subcortical white matter lesions

    Science.gov (United States)

    van der Lijn, Fedde; Vernooij, Meike W.; Ikram, M. Arfan; Vrooman, Henri A.; Rueckert, Daniel; Hammers, Alexander; Breteler, Monique M. B.; Niessen, Wiro J.

    2007-03-01

    It is still unclear whether periventricular and subcortical white matter lesions (WMLs) differ in etiology or clinical consequences. Studies addressing this issue would benefit from automated segmentation and localization of WMLs. Several papers have been published on WML segmentation in MR images. Automated localization however, has not been investigated as much. This work presents and evaluates a novel method to label segmented WMLs as periventricular and subcortical. The proposed technique combines tissue classification and registration-based segmentation to outline the ventricles in MRI brain data. The segmented lesions can then be labeled into periventricular WMLs and subcortical WMLs by applying region growing and morphological operations. The technique was tested on scans of 20 elderly subjects in which neuro-anatomy experts manually segmented WMLs. Localization accuracy was evaluated by comparing the results of the automated method with a manual localization. Similarity indices and volumetric intraclass correlations between the automated and the manual localization were 0.89 and 0.95 for periventricular WMLs and 0.64 and 0.89 for subcortical WMLs, respectively. We conclude that this automated method for WML localization performs well to excellent in comparison to the gold standard.

  2. White matter lesion progression

    DEFF Research Database (Denmark)

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C

    2015-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants asso...

  3. Severity of White Matter Lesions Correlates with Subcortical Diffusion-Weighted Imaging Abnormalities and Predicts Stroke Risk.

    Science.gov (United States)

    Fang, Hui; Zhao, Lu; Pei, Lulu; Song, Bo; Gao, Yuan; Liu, Kai; Xu, Yafang; Li, Yusheng; Wu, Jun; Xu, Yuming

    2017-08-31

    The severity of white matter lesions (WMLs) has been strongly linked to small-vessel diseases or lacunar infarction. The present study aimed to investigate the correlation between severity of WMLs and distribution of diffusion-weighted imaging (DWI) hyperintensities, and to explore whether the severity of WMLs is an independent neuroimaging predictor of stroke risk after transient symptoms with infarction (TSI). We evaluated the presence and severity of WMLs on fluid-attenuated inversion recovery sequences using the age-related white matter changes scale and the location and size of hyperintensities on DWI sequences, respectively, in a prospective cohort study of TSI patients. The primary end point was recurrent stroke within 90 days. A total of 191 consecutive TSI patients were eligible for inclusion in the present analysis. The average age of the patients was 57.3 ± 12.8 years. DWI abnormalities occurred more often in the deep white matter with increasing severity of WMLs (P matter in TSI patients and contributed to an increased risk of recurrent stroke. Copyright © 2017. Published by Elsevier Inc.

  4. Automated measurement of local white matter lesion volume

    DEFF Research Database (Denmark)

    van der Lijn, Fedde; Verhaaren, Benjamin F. J.; Ikram, M. Arfan

    2012-01-01

    It has been hypothesized that white matter lesions at different locations may have different etiology and clinical consequences. Several approaches for the quantification of local white matter lesion load have been proposed in the literature, most of which rely on a distinction between lesions...... in a periventricular region close to the ventricles and a subcortical zone further away. In this work we present a novel automated method for local white matter lesion volume quantification in magnetic resonance images. The method segments and measures the white matter lesion volume in 43 regions defined...... by orientation and distance to the ventricles, which allows a more spatially detailed study of lesion load. The potential of the method was demonstrated by analyzing the effect of blood pressure on the regional white matter lesion volume in 490 elderly subjects taken from a longitudinal population study...

  5. Marchiafava-Bignami disease: magnetic resonance imaging findings in corpus callosum and subcortical white matter

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    Kawarabuki, Kentaro E-mail: bukky@h2.dion.ne.jp; Sakakibara, Takehiko; Hirai, Makoto; Yoshioka, Yuji; Yamamoto, Yasumasa; Yamaki, Tarumi

    2003-11-01

    A case of Marchiafava-Bignami disease (MBD) is presented using magnetic resonance imaging (MRI). A patient with a long history of alcoholism developed a gait disturbance with involuntary movements at the lower extremities. MRI scans taken at the onset showed no particular abnormalities. He progressed to a coma 10 days later. MRI scans taken 20 days after the onset showed a focal lesion at the genu of the corpus callosum and he was diagnosed as having MBD. In addition, multiple lesions were observed in bilateral frontoparietal subcortical white matter. These lesions demonstrated similar intense MRI signals as the corpus callosum.

  6. A case of Jacobsen syndrome with multifocal white matter lesions.

    Science.gov (United States)

    Yu, Fang; Carter, John E; Bazan, Carlos

    2016-01-01

    Jacobsen syndrome is a rare disorder caused by partial deletions of the long arm of chromosome 11. The phenotype is variable with involvement of multiple organ systems, resulting in congenital heart defects, blood dyscrasias, and impaired growth. We describe a case of a 30-year-old man with multiple ophthalmic manifestations and brain magnetic resonance imaging (MRI) that was remarkable for multiple T2-hyperintense subcortical white matter lesions. It is important to be aware that patients with Jacobsen syndrome may have nonspecific white changes seen on MRI. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. White Matter Lesion Progression in LADIS

    DEFF Research Database (Denmark)

    Schmidt, Reinhold; Berghold, Andrea; Jokinen, Hanna

    2012-01-01

    BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample...... grade on the Rotterdam Progression Scale. RESULTS: WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment...... effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm...

  8. Associations Between T1 White Matter Lesion Volume and Regional White Matter Microstructure in Aging

    OpenAIRE

    Leritz, Elizabeth C.; Shepel, Juli; Williams, Victoria J.; Lipsitz, Lewis A; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.

    2013-01-01

    White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually ...

  9. Associations between T1 white matter lesion volume and regional white matter microstructure in aging.

    Science.gov (United States)

    Leritz, Elizabeth C; Shepel, Juli; Williams, Victoria J; Lipsitz, Lewis A; McGlinchey, Regina E; Milberg, William P; Salat, David H

    2014-03-01

    White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43-85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. Copyright © 2013 Wiley Periodicals, Inc.

  10. Cerebral white matter lesions and depressive symptoms in elderly adults

    NARCIS (Netherlands)

    J.C. de Groot (Jan Cees); H.F. de Leeuw (Frank); M. Oudkerk (Matthijs); J. Jolles (Jellemer); M.M.B. Breteler (Monique); A. Hofman (Albert)

    2000-01-01

    textabstractBACKGROUND: There is evidence for a vascular cause of late-life depression. Cerebral white matter lesions are thought to represent vascular abnormalities. White matter lesions have been related to affective disorders and a history of late-onset depression in

  11. Quantitative analysis of [{sup 18}F]FDDNP PET using subcortical white matter as reference region

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    Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Liu, Jie; Satyamurthy, Nagichettiar; Barrio, Jorge R. [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Wardak, Mirwais; Huang, Sung-Cheng [David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Department of Biomathematics, Los Angeles, CA (United States); Small, Gary W. [David Geffen School of Medicine at UCLA, Department of Psychiatry and Biobehavioral Sciences, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA (United States); David Geffen School of Medicine at UCLA, UCLA Center on Aging, Los Angeles, CA (United States); Mary S. Easton Center for Alzheimer' s Disease Research, Los Angeles, CA (United States)

    2010-03-15

    Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimer's disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [{sup 18}F]FDDNP binding in the human brain. Dynamic [{sup 18}F]FDDNP PET studies were performed on 7 control subjects and 12 AD patients. Population efflux rate constants (k{sup '}{sub 2}) from subcortical white matter (centrum semiovale) and cerebellar cortex were derived by a simplified reference tissue modeling approach incorporating physiological constraints. Regional distribution volume ratio (DVR) estimates were derived using Logan and simplified reference tissue approaches, with either subcortical white matter or cerebellum as reference input. Discriminant analysis with cross-validation was performed to classify control subjects and AD patients. The population estimates of k{sup '}{sub 2} in subcortical white matter did not differ significantly between control subjects and AD patients but the variability of individual estimates of k{sup '}{sub 2} determined in white matter was lower than that in cerebellum. Logan DVR showed dependence on the efflux rate constant in white matter. The DVR estimates in the frontal, parietal, posterior cingulate, and temporal cortices were significantly higher in the AD group (p<0.01). Incorporating all these regional DVR estimates as predictor variables in discriminant analysis yielded accurate classification of control subjects and AD patients with high sensitivity and specificity, and the results agreed well with those using the cerebellum as the reference region. Subcortical white matter can be used as a reference region for quantitative analysis of [{sup 18}F]FDDNP with the Logan method which allows more accurate and less biased binding estimates, but a population efflux rate constant has to be determined a priori. (orig.)

  12. The brain subcortical white matter and aging: A quantitative fractional anisotropy analysis

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Abstract To study the integrity of hemispheric subcortical white matter by comparing normal young and elderly subjects using quantitative fractional anisotropy (DTI-FA. Methods: Subjects of two different age groups (young=12, elderly=12 were included. MR - GE Signa Horizon - 1.5T scans were performed. Cases with Fazekas scores £3 were assessed on FLAIR sequence. Standard parameters for DTI-FA were used. ROIs were placed at various sites of the subcortical white matter, and the genu and splenium of the midline corpus callosum. Analysis was performed using Functool. Statistics for anterior and posterior white matter, as well as the genu and splenium were compared between the groups. The study was approved by the Ethics Committee of IPUB-UFRJ and informed consent obtained. Results: DTI-FA showed lower anisotropy values in the anterior region (subcortical white matter and genu, but not in the posterior region (subcortical white matter and splenium, in elderly normal subjects compared to young subjects. Conclusion: The results may represent loss of integrity of anterior (frontal white matter fibers in the elderly subjects. These fibers constitute important intra- and inter-hemispheric tracts, components of neural networks that provide cognitive, behavioral, motor and sensory integration. The loss of integrity of the anterior segments of the studied fiber systems with ageing, represents a disconnection process that may underlie clinical manifestations found in elderly subjects such as executive dysfunction.

  13. Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD.

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    Martinez-Vea, Alberto; Salvadó, Esther; Bardají, Alfredo; Gutierrez, Cristina; Ramos, Ana; García, Carmen; Compte, Teresa; Peralta, Carmen; Broch, Montse; Pastor, Rosa; Angelet, Pere; Marcas, Luis; Saurí, Amadeo; Oliver, Jesús Angel

    2006-02-01

    Silent cerebral white matter lesions are observed on magnetic resonance imaging (MRI) scans in elderly people, and they are related to vascular risk factors, particularly hypertension. No data on the prevalence and risk factors of white matter lesions in patients with chronic kidney disease (CKD) are available. The aim is to analyze the prevalence of white matter lesions and their determinants in this population. We studied 52 patients without diabetes with CKD (stage 3 or 4) aged 30 to 60 years (average, 49 years) and a group of 32 normotensive control subjects. MRI studies were performed and subcortical and periventricular white matter lesions were evaluated by using semiquantitative measures. Patients were classified into 2 groups depending on the presence or absence of white matter lesions. Echocardiographic studies and measures of markers of systemic inflammation (C-reactive protein and interleukin 6) also were performed. White matter lesions were more prevalent in patients with CKD than controls (33% versus 6%; P = 0.008). Patients with CKD who had white matter lesions were older; had a greater history of cardiovascular disease and vascular nephropathy as a primary cause of renal disease and greater levels of systolic blood pressure, pulse pressure, left ventricular mass index, and C-reactive protein; and were administered more antihypertensive drugs than patients with CKD without white matter lesions. Stage and duration of CKD were not related to the presence of white matter lesions. After adjusting for several factors, only vascular nephropathy (odds ratio, 15.6; 95% confidence interval, 1.27 to 191.54; P = 0.03) independently predicted an increased risk for white matter lesions. One third of middle-aged patients with CKD have silent cerebral white matter lesions. Vascular nephropathy seems to be the most important factor related to the presence of these lesions, suggesting that white matter lesions reflect ischemic brain damage caused by generalized

  14. White matter lesion segmentation using robust parameter estimation algorithms

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    Yang, Faguo; Zhu, Litao; Jiang, Tianzi

    2003-05-01

    White matter lesions are common brain abnormalities. In this paper, we introduce an automatic algorithm for segmentation of white matter lesions from brain MRI images. The intensities of each tissue is assumed to be Gaussian distributed, whose parameters (mean vector and covariance matrix) are estimated using a tissue distribution model. And then a measure is defined to indicate in how much content a voxel belongs to the lesions. Experimental results demonstrate that our algorithm works well.

  15. Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

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    Hainsworth, Atticus H; Minett, Thais; Andoh, Joycelyn; Forster, Gillian; Bhide, Ishaan; Barrick, Thomas R; Elderfield, Kay; Jeevahan, Jamuna; Markus, Hugh S; Bridges, Leslie R

    2017-10-01

    We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P=0.007). Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers. © 2017 American Heart Association, Inc.

  16. The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism.

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    Coplan, Jeremy D; Hodulik, Sarah; Mathew, Sanjay J; Mao, Xiangling; Hof, Patrick R; Gorman, Jack M; Shungu, Dikoma C

    2011-01-01

    We have demonstrated in a previous study that a high degree of worry in patients with generalized anxiety disorder (GAD) correlates positively with intelligence and that a low degree of worry in healthy subjects correlates positively with intelligence. We have also shown that both worry and intelligence exhibit an inverse correlation with certain metabolites in the subcortical white matter. Here we re-examine the relationships among generalized anxiety, worry, intelligence, and subcortical white matter metabolism in an extended sample. Results from the original study were combined with results from a second study to create a sample comprised of 26 patients with GAD and 18 healthy volunteers. Subjects were evaluated using the Penn State Worry Questionnaire, the Wechsler Brief intelligence quotient (IQ) assessment, and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to measure subcortical white matter metabolism of choline and related compounds (CHO). Patients with GAD exhibited higher IQ's and lower metabolite concentrations of CHO in the subcortical white matter in comparison to healthy volunteers. When data from GAD patients and healthy controls were combined, relatively low CHO predicted both relatively higher IQ and worry scores. Relatively high anxiety in patients with GAD predicted high IQ whereas relatively low anxiety in controls also predicted high IQ. That is, the relationship between anxiety and intelligence was positive in GAD patients but inverse in healthy volunteers. The collective data suggest that both worry and intelligence are characterized by depletion of metabolic substrate in the subcortical white matter and that intelligence may have co-evolved with worry in humans.

  17. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Directory of Open Access Journals (Sweden)

    Sheng Xie

    Full Text Available Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  18. Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

    Science.gov (United States)

    Xie, Sheng; Zhang, Zhe; Chang, Feiyan; Wang, Yishi; Zhang, Zhenxia; Zhou, Zhenyu; Guo, Hua

    2016-01-01

    Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.

  19. Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

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    Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos

    2015-01-01

    Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

  20. Connecting Cerebral White Matter Lesions and Hypertensive Target Organ Damage

    Directory of Open Access Journals (Sweden)

    Cristina Sierra

    2011-01-01

    Full Text Available Chronic hypertension leads to concomitant remodeling of the cardiac and vascular systems and various organs, especially the brain, kidney, and retina. The brain is an early target of organ damage due to high blood pressure, which is the major modifiable risk factor for stroke and small vessel disease. Stroke is the second leading cause of death and the number one cause of disability worldwide and over 80% of strokes occur in the elderly. Preclinical hypertensive lesions in most target organs are clearly identified: left ventricular hypertrophy for the heart, microalbuminuria for the kidney, fundus abnormalities for the eye, and intima-media thickness and pulse wave velocity for the vessels. However, early hypertensive brain damage is not fully studied due to difficulties in access and the expense of techniques. After age, hypertension is the most-important risk factor for cerebral white matter lesions, which are an important prognostic factor for stroke, cognitive impairment, dementia, and death. Studies have shown an association between white matter lesions and a number of extracranial systems affected by high BP and also suggest that correct antihypertensive treatment could slow white matter lesions progression. There is strong evidence that cerebral white matter lesions in hypertensive patients should be considered a silent early marker of brain damage.

  1. Memory loss from a subcortical white matter infarct.

    OpenAIRE

    Kooistra, C A; Heilman, K M

    1988-01-01

    Clinical disorders of memory are believed to occur from the dysfunction of either the mesial temporal lobe, the mesial thalamus, or the basal forebrain. Fibre tract damage at the level of the fornix has only inconsistently produced amnesia. A patient is reported who suffered a cerebrovascular accident involving the posterior limb of the left internal capsule that resulted in a persistent and severe disorder of verbal memory. The inferior extent of the lesion effectively disconnected the mesia...

  2. MRI white Matter Lesions in a Stroke Clinic Population: Correlation ...

    African Journals Online (AJOL)

    Cerebral white matter lesions (WML) on MRI have been related not only to age but also to cerebrovascular disorders. This study aimed to determine the prevalence of WML in a population of patients attending a stroke clinic and relate it to the presence of carotid atherosclerosis as determined by increased carotid ...

  3. Periventricular cerebral white matter lesions predict rate of cognitive decline

    NARCIS (Netherlands)

    de Groot, JC; de Leeuw, FE; Oudkerk, M; van Gijn, J; Hofman, A; Jolles, J; Breteler, MMB

    The prospect of declining cognitive functions is a major fear for many elderly persons. Cerebral white matter lesions, as commonly found with magnetic resonance imaging, have been associated with cognitive dysfunction in cross-sectional studies. Only a few longitudinal studies using small cohorts

  4. Focal central white matter lesions in Alexander disease.

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    Barreau, Pauline; Prust, Morgan J; Crane, Jeremy; Loewenstein, Johanna; Kadom, Nadja; Vanderver, Adeline

    2011-11-01

    Alexander disease is a neurodegenerative disorder of the central white matter caused by dominant mutations in GFAP, the gene encoding glial fibrillary acidic protein. Magnetic resonance imaging pattern recognition studies have established characteristic radiologic phenotypes for this disorder. In some cases, however, genetically confirmed cases do not express these features, and several reports have identified "atypical" radiologic findings in Alexander disease patients. Here, the authors report 3 genetically confirmed Alexander disease cases with focal central white matter lesions that, upon longitudinal clinical and radiologic evaluation, appear to reflect an atypical Alexander disease magnetic resonance imaging phenotype and not another pathophysiologic process such as encephalitis, infarction, or neoplasm.

  5. Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy.

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    Scheck, Simon M; Fripp, Jurgen; Reid, Lee; Pannek, Kerstin; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

    2016-08-01

    To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function. Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test). Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups. Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Automated detection of Lupus white matter lesions in MRI

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    Eloy Roura Perez

    2016-08-01

    Full Text Available Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML. In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM, gray matter (GM and cerebrospinal fluid (CSF, while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative and quantitative results in terms of precision and sensitivity of lesion detection (True Positive Rate (62% and Positive Prediction Value (80% respectively as well as segmentation accuracy (Dice Similarity Coefficient (72%. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration.

  7. Automated Detection of Lupus White Matter Lesions in MRI.

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    Roura, Eloy; Sarbu, Nicolae; Oliver, Arnau; Valverde, Sergi; González-Villà, Sandra; Cervera, Ricard; Bargalló, Núria; Lladó, Xavier

    2016-01-01

    Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML). In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR) images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative, and quantitative results in terms of precision and sensitivity of lesion detection [True Positive Rate (62%) and Positive Prediction Value (80%), respectively] as well as segmentation accuracy [Dice Similarity Coefficient (72%)]. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration.

  8. Intra- and interhemispheric variations of diffusivity in subcortical white matter in normal human brain

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    Yoshiura, Takashi; Noguchi, Tomoyuki; Hiwatashi, Akio; Togao, Osamu; Yamashita, Koji; Nagao, Eiki; Kamano, Hironori; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan)

    2010-01-15

    Our purpose was to reveal potential regional variations in water molecular diffusivity within each cerebral hemisphere and across the right and left hemispheres. Diffusion-weighted images of 44 healthy right-handed adult male subjects were obtained using a diffusion tensor imaging sequence. Mean diffusivity (MD) values in subcortical white matter (WM) within 39 regions in each hemisphere were measured using an automated method. Intrahemispheric comparisons of MDs in subcortical WM were performed among six brain regions (frontal, parietal, occipital and temporal lobes and pre- and postcentral gyri). Interhemispheric comparisons of MDs were performed between the right and left counterparts of the 39 regions. In both hemispheres, diffusivity in the precentral gyrus was lower than those in other regions, while diffusivity in the parietal lobe was higher than others. MD asymmetry in which the left was lower than the right was found in the parietal lobe, middle occipital gyrus, and medial and orbital aspects of the frontal lobe. The converse asymmetry was revealed in the frontal operculum, supplementary motor cortex, temporal lobe, limbic cortices, precuneus and cuneus. Our results revealed significant intra- and interhemispheric regional variations in MD in subcortical WM, which may be related to different densities of axons and myelin sheaths. (orig.)

  9. [Age-related white matter lesions (leukoaraiosis): an update].

    Science.gov (United States)

    Miki, Yukio; Sakamoto, Shinichi

    2013-07-01

    Leukoaraiosis (age-related white matter hyperintensities) is the most frequently seen lesion on brain magnetic resonance (MR) images. This lesion is a subject of much current interest, because a number of multicenter studies have revealed that it is associated with various disturbances and poor prognoses. Leukoaraiosis corresponds to various pathologies, including demyelination, apoptosis, edema, dilated perivascular spaces, axonal damage, gliosis, and infarcts. Also noted in leukoaraiosis are changes in small vessels, such as fibrohyalinosis and venous collagenosis. The main cause of leukoaraiosis is thought to be chronic ischemia; other causes include edema and breakdown of the blood-brain barrier. Major risk factors for leukoaraiosis are age and hypertension. Disturbances that are related to leukoaraiosis include stroke, dementia, cognitive impairment, gait disturbance, fall, and depression. Leukoaraiosis is also a risk factor for death. Technologies, such as automatic volumetry, tissue segmentation, diffusion tensor imaging, magnetization tensor imaging, diffusion kurtosis imaging, and ultra-high field MR imaging may provide further insights into leukoaraiosis.

  10. Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques.

    Science.gov (United States)

    Valdés Hernández, Maria Del C; Gallacher, Peter J; Bastin, Mark E; Royle, Natalie A; Maniega, Susana Muñoz; Deary, Ian J; Wardlaw, Joanna M

    2012-02-01

    White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named 'Multispectral Coloring Modulation and Variance Identification' (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T(1)-, T(2)-, T(2)⁎- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland-Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Transient Global Amnesia with Reversible White Matter Lesions: A Variant of Posterior Reversible Encephalopathy Syndrome?

    Directory of Open Access Journals (Sweden)

    Tomoki Nakamizo

    2015-01-01

    Full Text Available Transient global amnesia (TGA is a self-limited disease characterized by isolated amnesia, which resolves within 24 h. In contrast, posterior reversible encephalopathy syndrome (PRES is a potentially life-threatening disease that usually presents with seizures, altered mental status, headache, and visual disturbances. It is characterized by reversible vasogenic edema that predominantly involves the parieto-occipital subcortical white matter as shown by neuroimaging studies. To date, there have been no reported cases of PRES with a clinical course resembling TGA. Here we report the case of a 58-year-old woman who presented with isolated amnesia and headache. On admission, her blood pressure was 187/100 mmHg. She had complete anterograde amnesia and slight retrograde amnesia without other neurological findings. After the treatment of her hypertension, the amnesia resolved within 24 h. Although the initial magnetic resonance image (MRI was almost normal, the fluid attenuation inversion recovery (FLAIR images of the MRI on the next day revealed several small foci of high intensity areas in the fronto-parieto-occipital subcortical white matter, presumed to be vasogenic edema in PRES. The lesions disappeared one month later. This case suggests that PRES can mimic the clinical course of TGA. PRES should be considered in the differential diagnosis for TGA.

  12. Detection of white matter lesions in cerebral small vessel disease

    Science.gov (United States)

    Riad, Medhat M.; Platel, Bram; de Leeuw, Frank-Erik; Karssemeijer, Nico

    2013-02-01

    White matter lesions (WML) are diffuse white matter abnormalities commonly found in older subjects and are important indicators of stroke, multiple sclerosis, dementia and other disorders. We present an automated WML detection method and evaluate it on a dataset of small vessel disease (SVD) patients. In early SVD, small WMLs are expected to be of importance for the prediction of disease progression. Commonly used WML segmentation methods tend to ignore small WMLs and are mostly validated on the basis of total lesion load or a Dice coefficient for all detected WMLs. Therefore, in this paper, we present a method that is designed to detect individual lesions, large or small, and we validate the detection performance of our system with FROC (free-response ROC) analysis. For the automated detection, we use supervised classification making use of multimodal voxel based features from different magnetic resonance imaging (MRI) sequences, including intensities, tissue probabilities, voxel locations and distances, neighborhood textures and others. After preprocessing, including co-registration, brain extraction, bias correction, intensity normalization, and nonlinear registration, ventricle segmentation is performed and features are calculated for each brain voxel. A gentle-boost classifier is trained using these features from 50 manually annotated subjects to give each voxel a probability of being a lesion voxel. We perform ROC analysis to illustrate the benefits of using additional features to the commonly used voxel intensities; significantly increasing the area under the curve (Az) from 0.81 to 0.96 (p<0.05). We perform the FROC analysis by testing our classifier on 50 previously unseen subjects and compare the results with manual annotations performed by two experts. Using the first annotator results as our reference, the second annotator performs at a sensitivity of 0.90 with an average of 41 false positives per subject while our automated method reached the same

  13. FOD Restoration for Enhanced Mapping of White Matter Lesion Connectivity.

    Science.gov (United States)

    Sun, Wei; Amezcua, Lilyana; Shi, Yonggang

    2017-09-01

    To achieve improved understanding of white matter (WM) lesions and their effect on brain functions, it is important to obtain a comprehensive map of their connectivity. However, changes of the cellular environment in WM lesions attenuate diffusion MRI (dMRI) signals and make the robust estimation of fiber orientation distributions (FODs) difficult. In this work, we integrate techniques from image inpainting and compartment modeling to develop a novel method for enhancing FOD estimation in WM lesions from multi-shell dMRI, which is becoming increasingly popular with the success of the Human Connectome Project (HCP). By using FODs estimated from normal WM as the boundary condition, our method iteratively cycles through two key steps: diffusion-based inpainting and FOD reconstruction with compartment modeling for the successful restoration of FODs in WM lesions. In our experiments, we carry out extensive simulations to quantitatively demonstrate that our method outperforms a state-of-the-art method in angular accuracy and compartment parameter estimation. We also apply our method to multi-shell imaging data from 23 multiple sclerosis (MS) patients and one LifeSpan subject of HCP with WM lesion. We show that our method achieves superior performance in mapping the connectivity of WM lesions with FOD-based tractography.

  14. Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson's disease with and without dementia and in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Hanyu, H.; Asano, T.; Sakurai, H.; Takasaki, M. [Dept. of Geriatric Medicine, Tokyo Medical University (Japan); Shindo, H.; Abe, K. [Dept. of Radiology, Tokyo Medical University (Japan)

    2001-07-01

    We measured the magnetisation transfer ratio (MTR) in the subcortical grey and white matter of 11 patients with idiopathic Parkinson's disease (PD) without dementia, six with PD with dementia (PDD), six with progressive supranuclear palsy (PSP), and 12 elderly control subjects to assess regional differences in structural brain damage. There were no significant differences in MTR in any region between PD and controls. However, patients with PDD had significantly lower MTR in the subcortical white matter, including the frontal white matter and the genu of the corpus callosum than the controls, whereas PSP had significantly lower MTR in the subcortical grey matter, including the putamen, globus pallidus and thalamus, in addition to the subcortical white matter. This suggests that regional patterns of structural brain damage can be detected using the magnetisation transfer technique. Measurement of MTR in the subcortical grey and white matter may be useful in differential diagnosis. (orig.)

  15. Hypertension and cerebral white matter lesions in a prospective cohort study

    NARCIS (Netherlands)

    de Leeuw, FE; de Groot, JC; Oudkerk, M; Witteman, JCM; Hofman, A; van Gijn, J; Breteler, MMB

    White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hypertension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies.

  16. Fully Automatic Segmentation of White Matter Lesions from Multispectral Magnetic Resonance Imaging Data

    OpenAIRE

    Cui, Shenshen

    2010-01-01

    A fully automatic white matter lesion segmentation method has been developed and evaluated. The method uses multispectral magnetic resonance imaging (MRI) data (T1,T2 and Proton Density). First fuzzy c means (FCM) was used to segment normal brain tissues (white matter,grey matter, and cerebrospinal fluid). The holes in normal white matter were used to sample the WML intensities in the different images. The segmentation of WML was optimized by a graph cut approach. The method was trained by us...

  17. Correlation Between White Matter Lesions and Intelligence Quotient in Patients With Congenital Cytomegalovirus Infection.

    Science.gov (United States)

    Inaba, Yuji; Motobayashi, Mitsuo; Nishioka, Makoto; Kaneko, Tomoki; Yamauchi, Shoko; Kawasaki, Yoichiro; Shiba, Naoko; Nishio, Shin-ya; Moteki, Hideaki; Miyagawa, Maiko; Takumi, Yutaka; Usami, Shin-ichi; Koike, Kenichi

    2016-02-01

    It is well known that congenital cytomegalovirus infection exhibits white matter and other types of lesions in magnetic resonance imaging (MRI), but little is known on the clinical significance of white matter lesions because they are also present in asymptomatic congenital cytomegalovirus infection. We investigated for relationships among white matter lesions, intelligence quotient, and other neurodevelopmental features. Nine children (five boys and four girls; mean age: 87.4 months, range: 63-127 months) with sensorineural hearing loss (five bilateral and four unilateral) had been diagnosed as having congenital cytomegalovirus infection by positive polymerase chain reaction findings of dried umbilical cords. They were evaluated for the presence of autistic features, tested using Wechsler Intelligence Scale for Children-Fourth Edition for intelligence quotient, and underwent brain MRI to measure white matter lesion localization and volume. At the time of MRI examination (mean age: 69.4 months, range: 19-92 months), white matter lesions were detected in eight of nine patients. Five subjects were diagnosed as having autism spectrum disorders. We observed increased white matter lesion volume was associated with lower intelligence quotient scores (R(2) = 0.533, P = 0.026) but not with autism spectrum disorders. In individuals with congenital cytomegalovirus, an increased white matter lesion volume is associated with lower intelligence quotient scores but not with an increased likelihood of autistic behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Increased Pittsburgh Compound-B Accumulation in the Subcortical White Matter of Alzheimer's Disease Brain.

    Science.gov (United States)

    Wakabayashi, Yuichi; Ishii, Kazunari; Hosokawa, Chisa; Hyodo, Tomoko; Kaida, Hayato; Yamada, Minoru; Yagyu, Yukinobu; Tsurusaki, Masakatsu; Kozuka, Takenori; Sugimura, Kazuro; Murakami, Takamichi

    2017-03-13

    Using 11C-Pittsburgh compound B (PiB)-PET and MRI volume data, we investigated whether white matter (WM) PiB uptake in Alzheimer's disease (AD) brain is larger than that of cortical PiB uptake-negative (PiB-negative) brain. Forty-five subjects who underwent both PiB-PET and MRI were included in the study (32 AD patients with cortical PiB-positive and 13 cortical amyloid -negative patients). Individual areas of gray matter (GM) and WM were segmented, then regional GM and WM standard uptake value ratio (SUVR) normalized to cerebellar GM with partial volume effects correction was calculated. Three regional SUVRs except WM in the centrum semiovale in the AD group were significantly larger than those in the PiB-negative groups. Frontal WM SUVR in the AD group vs frontal WM SUVR in the PiB-negative group was 2.57 ± 0.55 vs 1.64 ± 0.22; parietal, 2.50 ± 0.52 vs 1.74 ± 0.22; posterior cingulate, 2.84 ± 0.59 vs 1.73 ± 0.22; and WM in the centrum semiovale, 2.21 ± 0.53 vs 2.42 ± 0.36, respectively. We found that PiB uptake in AD brain is significantly larger than that in PiB-negative brain in the frontal, parietal and posterior cingulate subcortical WM, except in the centrum semiovale.

  19. Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank imaging data.

    Science.gov (United States)

    Shen, Xueyi; Reus, Lianne M; Cox, Simon R; Adams, Mark J; Liewald, David C; Bastin, Mark E; Smith, Daniel J; Deary, Ian J; Whalley, Heather C; McIntosh, Andrew M

    2017-07-17

    Previous reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n = 1157) and white matter integrity (n = 1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β = -0.182, p = 0.005). We also found reductions in FA in association/commissural fibres (β = -0.184, pcorrected = 0.010) and thalamic radiations (β = -0.159, pcorrected = 0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β = -0.194, pcorrected = 0.025), superior thalamic radiation (β = -0.224, pcorrected = 0.009) and forceps major (β = -0.193, pcorrected = 0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.

  20. Cerebral white matter lesions and subjective cognitive dysfunction - The Rotterdam Scan Study

    NARCIS (Netherlands)

    de Groot, J.C.; de Leeuw, FE; Oudkerk, M; Hofman, A; Jolles, J; Breteler, MMB

    2001-01-01

    Objective: To determine the relationship between cerebral white matter lesions (WML) and subjective cognitive dysfunction. Background: Subjective cognitive dysfunction is present when a person perceives failures of cognitive function. When annoying enough, these failures will be expressed as

  1. White Matter Lesion Progression: Genome-Wide Search for Genetic Influences

    National Research Council Canada - National Science Library

    Hofer, Edith; Cavalieri, Margherita; Bis, Joshua; DeCarli, Charles; Fornage, Myriam; Sigurdsson, Sigurdur; Srikanth, Velandai; Trompet, Stella; Verhaaren, Benjamin; Wolf, Christiane; Yang, Qiong Fang; Adams, Hieab; Amouyel, Philippe; Beiser, Alexa; Buckley, Brendan M; Callisaya, Michele; Chauhan, Ganesh; De Craen, Anton J. M; Dufouil, Carole; Duijn, Cornelia; Ford, I; Freudenberger, Paul; Gottesman, Rebecca; Gudnason, Vilmundur; Heiss, Gerardo; Hofman, Albert; Lumley, Thomas; Martinez, Oliver; Mazoyer, Bernard; Moran, Chris; Niessen, Wiro; Phan, Thanh; Psaty, Bruce; Satizabal, Claudia L; Sattar, Naveed; Schilling, Sabrina; Shibata, Dean; Slagboom, Eline; Smith, G.D; Stott, David. J; Taylor, Kent; Thomson, Russell; Töglhofer, Anna Maria; Tzourio, Christophe; Buchem, Mark; Wang, Jing; Westendorp, Rudi; Gwen Windham, B; Vernooij, Meike; Zijdenbos, A.P; Beare, Richard; Debette, Stéphanie; Ikram, Arfan; Jukema, Jan Wouter; Launer, Lenore; Longstreth, W.T; Mosley, Thomas H; Seshai, Sudha; Schmidt, Reinhold

    2015-01-01

    textabstractBackground and Purpose-White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown...

  2. Reversible white matter lesions during ketogenic diet therapy in glucose transporter 1 deficiency syndrome.

    Science.gov (United States)

    Shiohama, Tadashi; Fujii, Katsunori; Takahashi, Satoru; Nakamura, Fumito; Kohno, Yoichi

    2013-12-01

    Glucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport. We describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene. We initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet. This is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Evaluation of white matter lesions by diffusion tensor MR imaging. Preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Takeharu; Ohtomo, Kuni [Tokyo Univ. (Japan). Faculty of Medicine; Aoki, Shigeki; Ishigame, Keiichi; Araki, Tsutomu; Kabasawa, Hiroyuki

    2000-11-01

    Diffusion tensor imaging (DTI) represents diffusion anisotropy or directional difference of water diffusion. We preliminarily studied normal volunteers and patients with DTI using single-shot echo planar imaging. DTI was performed easily within a few minutes in all examinations. Fractional anisotropy of white matter lesions was decreased in pathological conditions. DTI is considered to be useful to estimate white matter of the brain, especially in diagnosis of myelination, secondary degeneration, and demyelinating and degenerative disease. (author)

  4. MRI of paraventricular white matter lesions in amyotrophic lateral sclerosis. Analysis by diffusion-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Segawa, Fuminori; Kinoshita, Masao (Toho Univ., Tokyo (Japan). Ohashi Hospital); Kishibayashi, Jun; Kamada, Kazuhiko; Sunohara, Nobuhiko

    1994-09-01

    Magnetic resonance images in some cases of amyotrophic lateral sclerosis (ALS) revealed abnormal signals in both the paraventriculer white matter and in the posterior limbs of the internal capsule. We examined T[sub 2]- and diffusion-weighted MR images of these lesions in 18 cases of ALS. There were symmetrical high-signal areas in the posterior limbs of the internal capsule in all of the cases. The high-signal areas in the internal capsule corresponded to the pyramidal tracts in the anatomical atlas by Talairach. In 5 of the cases of ALS, T[sub 2]-weighted MR images showed discrete paraventricular white matter lesions as well. The mean age of the ALS patients with paraventricular white matter lesions was higher than that of the ALS patients without such lesions. Proton densities calculated from the conventional MR images were higher in both the capsular and paraventricular lesions. The diffusion coefficients perpendicular to the pyramidal tract in the internal capsular lesions were within the normal range, where as the diffusion coefficients in the paraventricular lesions were increased in all directions. Thus, diffusion anisotropy was lost in the paraventricular lesions. These findings are similar to those observed in the white matter lesions of cerebro-vascular origin. As a result, the pathology of the paraventricular lesions in ALS was confirmed to be different from that of the internal capsular lesions. (author).

  5. Seven-Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions.

    Science.gov (United States)

    Chou, I-Jun; Lim, Su-Yin; Tanasescu, Radu; Al-Radaideh, Ali; Mougin, Olivier E; Tench, Christopher R; Whitehouse, William P; Gowland, Penny A; Constantinescu, Cris S

    2017-09-25

    Fluid-attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization-transfer-weighted (MTw ) images in the detection of white matter lesions compared with 3T-FLAIR. Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3-dimensional (D) MTw and 3T-2D-FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated. Of 662 lesions identified on 3T-2D-FLAIR images, 652 were detected on 7T-3D-MTw images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T-3D-MTw images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T-2D-FLAIR images (ICC 96.1% and 96.7%). Seven-Tesla MTw sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T-MTw imaging is a robust alternative for detecting demyelinating lesions in addition to 3T-FLAIR. Future studies need to compare the roles of optimized 7T-FLAIR and of 7T-MTw imaging. © 2017 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

  6. White Matter MS-Lesion Segmentation Using a Geometric Brain Model.

    OpenAIRE

    Strumia Maddalena; Schmidt Frank; Anastasopoulos Constantin; Granziera Cristina; Krueger Gunnar; Brox Thomas

    2016-01-01

    Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result the method is independent of an ...

  7. Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis.

    Science.gov (United States)

    Levy-Cooperman, Naama; Ramirez, Joel; Lobaugh, Nancy J; Black, Sandra E

    2008-04-01

    MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18). An automated tissue segmentation protocol that was optimized for an elderly population, a brain regional parcellation procedure, and a lesion segmentation protocol were applied to measure tissue volumes (whole brain and regional lobar volumes) with and without lesion segmentation to quantify the volume of misclassified tissue. After application of the tissue segmentation protocol and lesion analysis, mean total percentage misclassified volume across all subjects was 2% (17.9 cm(3)) of whole brain volume (corrected for total intracranial capacity). Mean percentage of misclassified tissue volumes for the severe group was 4.8% of whole brain, which translates to a mean volume 42.2 cm(3). Gray matter volume was most overestimated in the severe group, where 6.4% of the total gray matter volume was derived from misclassified WMH. The regional analysis showed that frontal (41%, 7.4 cm(3)) and inferior parietal (18%, 3.25 cm(3)) lobes were most affected by tissue misclassification. MRI-based volumetric studies of Alzheimer Disease that do not account for WMH can expect an erroneous inflation of gray or white matter volumes, especially in the frontal and inferior parietal regions. To avoid this source of error, MRI-based volumetric studies in patient populations susceptible to hyperintensities should include a WMH segmentation protocol.

  8. Extensive white matter hyperintensities may increase brain volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    Science.gov (United States)

    Yao, Ming; Jouvent, Eric; During, Marco; Godin, Ophélia; Hervé, Dominique; Guichard, Jean Pierre; Zhu, Yi-Cheng; Gschwendtner, Andreas; Opherk, Christian; Dichgans, Martin; Chabriat, Hugues

    2012-12-01

    The extent of white matter hyperintensities (WMH) is associated with cerebral atrophy in elderly people. WMH is a radiological hallmark of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but their relationship with brain volume remains poorly understood. The association between WMH and brain volume was analyzed in a large population of patients with CADASIL. Demographic and MRI data of 278 patients recruited from a prospective cohort study were analyzed. Volumes of WMH and lacunar infarcts, number of cerebral microbleeds, and brain parenchymal fraction were measured. Multivariate analysis was used to study the impact of WMH on brain volume at baseline. In univariate analyses, brain parenchymal fraction was negatively associated with age, male sex, and all MRI markers. Multiple regression modeling showed that brain parenchymal fraction was inversely related to age, number of cerebral microbleeds, and normalized volume of lacunar infarcts but positively related to normalized volume of WMH (Pbrain parenchymal fraction ≥86.37% (median values, both P≤0.001). The results of the present study suggest that extensive WMH may be associated with increase of brain volume in CADASIL. In this disorder, WMH may be related not only to loss of white matter components, but also to a global increase of water content in the cerebral tissue.

  9. White Matter Lesions, Carotid and Coronary Atherosclerosis in Late-Onset Depression and Healthy Controls

    DEFF Research Database (Denmark)

    Devantier, Torben Albert; Nørgaard, Bjarne Linde; Poulsen, Mikael Kjær

    2016-01-01

    Background: Cerebral white matter lesions (WMLs) are more common in individuals with late-onset or late-life depression. It has been proposed that carotid atherosclerosis may predispose to WMLs by inducing cerebral hypoperfusion. This hemodynamic effect of carotid atherosclerosis could be importa...

  10. Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

    NARCIS (Netherlands)

    J.C. van Swieten (John); S. Staal (S.); L.J. Kappelle (Jaap); M.M.A. Derix (M. M A); J. van Gijn (Jan)

    1996-01-01

    textabstractForty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on

  11. The presence of brain white matter lesions in relation to preeclampsia and migraine

    NARCIS (Netherlands)

    Postma, I. R.; van Oosterhout, W. P. J.; de Groot, J. C.; Terwindt, G. M.; Zeeman, G. G.

    Introduction Identifying female-specific risk markers for cerebrovascular disease is becoming increasingly important. Both migraine and preeclampsia have been associated with higher incidence of brain white matter lesions (WML) and stroke. We assessed the association between WML and migraine among

  12. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    NARCIS (Netherlands)

    Jokinen, H.; Goncalves, N.; Vigario, R.; Lipsanen, J.; Fazekas, F.; Schmidt, R.; Barkhof, F.; Madureira, S.; Verdelho, A.; Inzitari, D.; Pantoni, L.; Erkinjuntti, T.

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in

  13. White matter lesion extension to automatic brain tissue segmentation on MRI.

    Science.gov (United States)

    de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

    2009-05-01

    A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

  14. Serum carotenoids and cerebral white matter lesions : The Rotterdam Scan Study

    NARCIS (Netherlands)

    den Heijer, T; Launer, LJ; de Groot, JG; de Leeuw, FE; Oudkerk, M; van Gijn, J; Hofman, A; Breteler, MMB

    OBJECTIVES: To study the relation between serum levels of carotenoids and white matter lesions (WMLs) on magnetic resonance imaging (MRI). DESIGN: Evaluation of cross-sectional data from a cohort study. SETTING: The Rotterdam Scan Study. PARTICIPANTS: Two hundred and three nondemented older persons,

  15. Abnormal functional connectivity density in patients with ischemic white matter lesions: An observational study.

    Science.gov (United States)

    Ding, Ju-Rong; Ding, Xin; Hua, Bo; Xiong, Xingzhong; Wang, Qingsong; Chen, Huafu

    2016-09-01

    White matter lesions (WMLs) are frequently detected in elderly people. Previous structural and functional studies have demonstrated that WMLs are associated with cognitive and motor decline. However, the underlying mechanism of how WMLs lead to cognitive decline and motor disturbance remains unclear. We used functional connectivity density mapping (FCDM) to investigate changes in brain functional connectivity in 16 patients with ischemic WMLs and 13 controls. Both short- and long-range FCD maps were computed, and group comparisons were performed between the 2 groups. A correlation analysis was further performed between regions with altered FCD and cognitive test scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) in the patient group. We found that patients with ischemic WMLs showed reduced short-range FCD in the temporal cortex, primary motor cortex, and subcortical region, which may account for inadequate top-down attention, impaired motor, memory, and executive function associated with WMLs. The positive correlation between primary motor cortex and MoCA scores may provide evidence for the influences of cognitive function on behavioral performance. The inferior parietal cortex exhibited increased short-range FCD, reflecting a hyper bottom-up attention to compensate for the inadequate top-down attention for language comprehension and information retrieval in patients with WMLs. Moreover, the prefrontal and primary motor cortex showed increased long-range FCD and the former positively correlated with MoCA scores, which may suggest a strategy of cortical functional reorganization to compensate for motor and executive deficits. Our findings provide new insights into how WMLs cause cognitive and motor decline from cortical functional connectivity perspective.

  16. Neonatal deep white matter venous infarction and liquefaction: a pseudo-abscess lesion

    Energy Technology Data Exchange (ETDEWEB)

    Ruess, Lynne; Rusin, Jerome A. [Nationwide Children' s Hospital, Department of Radiology, Columbus, OH (United States); The Ohio State University College of Medicine and Public Health, Columbus, OH (United States); Dent, Carly M.; Tiarks, Hailey J.; Yoshida, Michelle A. [Nationwide Children' s Hospital, Department of Radiology, Columbus, OH (United States)

    2014-11-15

    Deep white matter hemorrhagic venous infarction with subsequent cavitation due to necrosis and liquefaction has been described in neonates and may be associated with infection and meningitis. In our experience, the MRI pattern of these lesions is confused with the pattern seen with cerebral abscesses. The purpose of our study was to characterize the MRI findings of post infarction necrosis and liquefaction after hemorrhagic deep white matter venous infarction in infants and to distinguish these lesions from cerebral abscesses. An institutional review board approved a retrospective review of imaging records to identify all patients with cerebral venous infarction at a children's hospital during a 10-year period. Nine infants had deep white matter hemorrhagic venous infarction with white matter fluid signal cavitary lesions. A diagnosis of cerebral abscess was considered in all. The imaging and laboratory findings in these patients are reviewed and compared to descriptions of abscesses found in the literature. There were six female and three male infants. The mean age at presentation was 20 days (range: 0-90 days), while the corrected age at presentation was less than 30 days for all patients. Seven patients presented with seizures and signs of infection; one infant presented with lethargy and later proved to have protein C deficiency. MRI was performed 0-12 days from presentation in these eight patients. Another patient with known protein C deficiency underwent MRI at 30 days for follow-up of screening US abnormalities. There were a total of 38 deep cerebral white matter fluid signal cavitary lesions: 25 frontal, 9 parietal, 2 temporal, 2 occipital. Larger lesions had dependent debris. All lesions had associated hemorrhage and many lesions had evidence of adjacent small vessel venous thrombosis. Lesions imaged after gadolinium showed peripheral enhancement. Three lesions increased in size on follow-up imaging. Three patients, two with meningitis confirmed via

  17. Computerized evaluation method of white matter hyperintensities related to subcortical vascular dementia in brain MR images

    Science.gov (United States)

    Arimura, Hidetaka; Kawata, Yasuo; Yamashita, Yasuo; Magome, Taiki; Ohki, Masafumi; Toyofuku, Fukai; Higashida, Yoshiharu; Tsuchiya, Kazuhiro

    2010-03-01

    We have developed a computerized evaluation method of white matter hyperintensity (WMH) regions for the diagnosis of vascular dementia (VaD) based on magnetic resonance (MR) images, and implemented the proposed method as a graphical interface program. The WMH regions were segmented using either a region growing technique or a level set method, one of which was selected by using a support vector machine. We applied the proposed method to MR images acquired from 10 patients with a diagnosis of VaD. The mean similarity index between WMH regions determined by a manual method and the proposed method was 78.2+/-11.0%. The proposed method could effectively assist neuroradiologists in evaluating WMH regions.

  18. Automatic identification of gray matter structures from MRI to improve the segmentation of white matter lesions.

    Science.gov (United States)

    Warfield, S; Dengler, J; Zaers, J; Guttmann, C R; Wells, W M; Ettinger, G J; Hiller, J; Kikinis, R

    1995-01-01

    The segmentation of MRI scans of patients with white matter lesions (WML) is difficult because the MRI characteristics of WML are similar to those of gray matter. Intensity-based statistical classification techniques misclassify some WML as gray matter and some gray matter as WML. We developed a fast elastic matching algorithm that warps a reference data set containing information about the location of the gray matter into the approximate shape of the patient's brain. The region of white matter was segmented after segmenting the cortex and deep gray matter structures. The cortex was identified by using a three-dimensional, region-growing algorithm that was constrained by anatomical, intensity gradient, and tissue class parameters. White matter and WML were then segmented without interference from gray matter by using a two-class minimum-distance classifier. Analysis of double-echo spin-echo MRI scans of 16 patients with clinically determined multiple sclerosis (MS) was carried out. The segmentation of the cortex and deep gray matter structures provided anatomical context. This was found to improve the segmentation of MS lesions by allowing correct classification of the white matter region despite the overlapping tissue class distributions of gray matter and MS lesion.

  19. Increased number of white matter lesions in patients with familial cerebral cavernous malformations.

    Science.gov (United States)

    Golden, M J; Morrison, L A; Kim, H; Hart, B L

    2015-05-01

    Familial cerebral cavernous malformations, an autosomal dominant disorder, result in excess morbidity and mortality in affected patients. The disorder is most prevalent in the Southwest United States, where the affected families are most often carriers of the CCM1-KRIT1 Common Hispanic Mutation. The brain and spinal cord parenchyma in these individuals is usually affected by multiple cavernous malformations. Previous studies have shown abnormalities of endothelial cell junctions and the blood-brain barrier in cerebral cavernous malformations. Endothelial cell abnormalities have also been described in pathologic studies of white matter hyperintensities. We compared the prevalence of white matter hyperintensities in a population with known familial cerebral cavernous malformations. We examined 191 subjects with familial cerebral cavernous malformations who were enrolled into an institutional review board-approved study. All carry the same Common Hispanic Mutation in the CCM1 gene. Each subject underwent 3T MR imaging, including gradient recalled-echo, SWI, and FLAIR sequences. The number of cavernous malformations and the number of nonhemorrhagic white matter hyperintensities were counted. Subjects older than 60 years of age were excluded due to the high prevalence of white matter lesions in this population, and children younger than 6 were excluded due to potential sedation requirements. Logistic regression analysis was performed to determine the prevalence of abnormal white matter hyperintensities in those with familial cerebral cavernous malformations compared with healthy controls or those with sporadic cerebral cavernous malformation within the familial cerebral cavernous malformations group; it was also performed to evaluate the associations between abnormal white matter hyperintensities and age, sex, headaches, thyroid disease, diabetes, hypertension, hyperlipidemia, seizure history, or modified Rankin Scale score. Familial CCM1 carriers have a higher

  20. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Kyle C. Kern

    2017-05-01

    Full Text Available Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1 identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2 compare this relationship across blood pressure groups, and (3 relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

  1. Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions.

    Science.gov (United States)

    Kern, Kyle C; Wright, Clinton B; Bergfield, Kaitlin L; Fitzhugh, Megan C; Chen, Kewei; Moeller, James R; Nabizadeh, Nooshin; Elkind, Mitchell S V; Sacco, Ralph L; Stern, Yaakov; DeCarli, Charles S; Alexander, Gene E

    2017-01-01

    Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1) identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2) compare this relationship across blood pressure groups, and (3) relate it to cognitive performance. In this group of participants aged 60-86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

  2. "Venous congestion" as a cause of subcortical white matter T2 hypointensity on magnetic resonance images

    Directory of Open Access Journals (Sweden)

    Jayaprakash Harsha Kamble

    2016-01-01

    Full Text Available Subcortical T2 hypointensity is an uncommon finding seen in very limited conditions such as multiple sclerosis, Sturge-Weber syndrome, and meningitis. Some of the conditions such as moyamoya disease, severe ischemic-anoxic insults, early cortical ischemia, and infarcts are of "arterial origin." We describe two conditions in which "venous congestion" plays a major role in T2 hypointensity - cerebral venous sinus thrombosis (CVST and dural arteriovenous fistula (dAVF. The third case is a case of meningitis, showing T2 hypointensity as well, and can be explained by the "venous congestion" hypothesis. The same hypothesis can explain few of the other conditions causing subcortical T2 hypointensity.

  3. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging

    OpenAIRE

    Barber, R; Scheltens, P.; Gholkar, A.; Ballard, C; McKeith, I; Ince, P.; Perry, R.; O'Brien, J

    1999-01-01

    OBJECTIVES—Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.
METHODS—Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI sca...

  4. Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

    Science.gov (United States)

    Datta, Gourab; Colasanti, Alessandro; Rabiner, Eugenii A; Gunn, Roger N; Malik, Omar; Ciccarelli, Olga; Nicholas, Richard; Van Vlierberghe, Eline; Van Hecke, Wim; Searle, Graham; Santos-Ribeiro, Andre; Matthews, Paul M

    2017-11-01

    Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnetization

  5. Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder

    Science.gov (United States)

    Myung, W; Han, C E; Fava, M; Mischoulon, D; Papakostas, G I; Heo, J-Y; Kim, K W; Kim, S T; Kim, D J H; Kim, D K; Seo, S W; Seong, J-K; Jeon, H J

    2016-01-01

    Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal

  6. Automated Bayesian segmentation of microvascular white-matter lesions in the ACCORD-MIND study.

    Science.gov (United States)

    Herskovits, E H; Bryan, R N; Yang, F

    2008-01-01

    Automatic brain-lesion segmentation has the potential to greatly expand the analysis of the relationships between brain function and lesion locations in large-scale epidemiologic studies, such as the ACCORD-MIND study. In this manuscript we describe the design and evaluation of a Bayesian lesion-segmentation method, with the expectation that our approach would segment white-matter brain lesions in MR images without user intervention. Each ACCORD-MIND subject has T1-weighted, T2-weighted, spin-density-weighted, and FLAIR sequences. The training portion of our algorithm first registers training images to a standard coordinate space; then, it collects statistics that capture signal-intensity information, and residual spatial variability of normal structures and lesions. The classification portion of our algorithm then uses these statistics to segment lesions in images from new subjects, without the need for user intervention. We evaluated this algorithm using 42 subjects with primarily white-matter lesions from the ACCORD-MIND project. Our experiments demonstrated high classification accuracy, using an expert neuroradiologist as a standard. A Bayesian lesion-segmentation algorithm that collects multi-channel signal-intensity and spatial information from MR images of the brain shows potential for accurately segmenting brain lesions in images obtained from subjects not used in training.

  7. White Matter Brain Lesions in Midlife Familial Hypercholesterolemic Patients at 3-Tesla Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, S.A.; O' Regan, D.P.; Fitzpatrick, J.; Neuwirth, C.; Potter, E.; Tosi, I.; Hajnal, J.V.; Naoumova, R.P. (Imaging Sciences Dept. and Clinical Research Facility, MRC Clinical Sciences Centre, London (GB))

    2008-03-15

    Background: Patients with hypercholesterolemia of 60 years and older have an increased risk for white matter brain lesions and dementia. Purpose: To investigate whether patients with familial hypercholesterolemia (FH) develop white matter lesions at 3-Tesla (T) MRI as early as in midlife. Material and Methods: Non-diabetic, non-smoking, and non-hypertensive heterozygous FH patients on treatment with maximally tolerated dose of a statin for more than 5 years (n = 14) and matched controls (n = 22) aged 25 to 60 years of age were studied. Imaging was performed at 3T with a fluid-attenuated T2-weighted MR pulse sequence and a T1-weighted spin-echo pulse sequence following 10 ml of i.v. gadopentetate dimeglumine. Images were evaluated by two independent readers. Fasting blood samples were taken. Student's t test was employed at P<0.05. Results: Three volunteers and one FH patient had white matter lesions (P<0.53). No other evidence of past ischemic stroke was observed. Mean total serum cholesterol and low-density lipoprotein (LDL) cholesterol were significantly higher in the FH group (6.0+-1.1 vs. 5.1+-0.9 mmol/l, P<0.02 and 4.1+-0.9 vs. 3.1+-0.8 mmol/l, P<0.004, respectively). Conclusion: Heterozygous FH patients on statin treatment in the age range of 25 to 60 years are not at increased risk of white matter lesions at 3T MRI

  8. An Optimized Clustering Approach for Automated Detection of White Matter Lesions in MRI Brain Images

    Directory of Open Access Journals (Sweden)

    M. Anitha

    2012-04-01

    Full Text Available Settings White Matter lesions (WMLs are small areas of dead cells found in parts of the brain. In general, it is difficult for medical experts to accurately quantify the WMLs due to decreased contrast between White Matter (WM and Grey Matter (GM. The aim of this paper is to
    automatically detect the White Matter Lesions which is present in the brains of elderly people. WML detection process includes the following stages: 1. Image preprocessing, 2. Clustering (Fuzzy c-means clustering, Geostatistical Possibilistic clustering and Geostatistical Fuzzy clustering and 3.Optimization using Particle Swarm Optimization (PSO. The proposed system is tested on a database of 208 MRI images. GFCM yields high sensitivity of 89%, specificity of 94% and overall accuracy of 93% over FCM and GPC. The clustered brain images are then subjected to Particle Swarm Optimization (PSO. The optimized result obtained from GFCM-PSO provides sensitivity of 90%, specificity of 94% and accuracy of 95%. The detection results reveals that GFCM and GFCMPSO better localizes the large regions of lesions and gives less false positive rate when compared to GPC and GPC-PSO which captures the largest loads of WMLs only in the upper ventral horns of the brain.

  9. Automatic white matter lesion segmentation using contrast enhanced FLAIR intensity and Markov Random Field.

    Science.gov (United States)

    Roy, Pallab Kanti; Bhuiyan, Alauddin; Janke, Andrew; Desmond, Patricia M; Wong, Tien Yin; Abhayaratna, Walter P; Storey, Elsdon; Ramamohanarao, Kotagiri

    2015-10-01

    White matter lesions (WMLs) are small groups of dead cells that clump together in the white matter of brain. In this paper, we propose a reliable method to automatically segment WMLs. Our method uses a novel filter to enhance the intensity of WMLs. Then a feature set containing enhanced intensity, anatomical and spatial information is used to train a random forest classifier for the initial segmentation of WMLs. Following that a reliable and robust edge potential function based Markov Random Field (MRF) is proposed to obtain the final segmentation by removing false positive WMLs. Quantitative evaluation of the proposed method is performed on 24 subjects of ENVISion study. The segmentation results are validated against the manual segmentation, performed under the supervision of an expert neuroradiologist. The results show a dice similarity index of 0.76 for severe lesion load, 0.73 for moderate lesion load and 0.61 for mild lesion load. In addition to that we have compared our method with three state of the art methods on 20 subjects of Medical Image Computing and Computer Aided Intervention Society's (MICCAI's) MS lesion challenge dataset, where our method shows better segmentation accuracy compare to the state of the art methods. These results indicate that the proposed method can assist the neuroradiologists in assessing the WMLs in clinical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Brain white matter lesions detected by magnetic resonance [correction of resosnance] imaging are associated with balance and gait speed.

    Science.gov (United States)

    Starr, J M; Leaper, S A; Murray, A D; Lemmon, H A; Staff, R T; Deary, I J; Whalley, L J

    2003-01-01

    To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults. 97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions. Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven's progressive matrices score (Raven score) (p balance was correlated with Raven score (p = 0.042), brain stem lesions (p = 0.003), white matter lesions (p = 0.003), and periventricular lesions (p = 0.038). Binary logistic regression identified brain stem lesions (odds ratio (OR) 0.22; 95% confidence interval 0.09 to 0.54) and HADS depression score (OR 0.75; 0.58 to 0.97) as the only significant associations with balance. Structural equation modelling detected an association between two latent traits representing white matter disease and an integrating function, respectively. In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.

  11. The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms.

    Science.gov (United States)

    O'Brien, J; Perry, R; Barber, R; Gholkar, A; Thomas, A

    2000-04-01

    A number of studies have suggested that cerebral changes, particularly deep white matter lesions (WML) visualized on magnetic resonance imaging (MRI), may be involved in the genesis of late life depression. This has been confirmed in a prospective study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects. Most studies find these lesions to predominate in frontal lobe and basal ganglia, supporting the hypothesis of "fronto-striatal" dysfunction in depression. To investigate whether WML are associated with mood disturbance in dementia, proton density and T2-weighted images were obtained in 80 subjects with dementia (dementia with Lewy bodies, n = 27; Alzheimer's disease, n = 28; vascular dementia, n = 25) and 26 age-matched normal controls. Periventricular lesions (PVL), white matter lesions (WML), and basal ganglia hyperintensities (BG) were visually rated blind to diagnosis using a semiquantitative scale. Frontal WML were associated with higher depression scores in patients with dementia, implying a common pathophysiology of depression irrespective of diagnosis. Further study of the neurobiological basis of WML is needed. This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination.

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

    DEFF Research Database (Denmark)

    Puonti, Oula; Van Leemput, Koen

    2016-01-01

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

  13. Age dependent white matter lesions and brain volume changes in healthy volunteers

    DEFF Research Database (Denmark)

    Christiansen, P; Larsson, H B; Thomsen, C

    1994-01-01

    was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males......The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles...

  14. Evaluating the effects of white matter multiple sclerosis lesions on the volume estimation of 6 brain tissue segmentation methods.

    Science.gov (United States)

    Valverde, S; Oliver, A; Díez, Y; Cabezas, M; Vilanova, J C; Ramió-Torrentà, L; Rovira, À; Lladó, X

    2015-06-01

    The accuracy of automatic tissue segmentation methods can be affected by the presence of hypointense white matter lesions during the tissue segmentation process. Our aim was to evaluate the impact of MS white matter lesions on the brain tissue measurements of 6 well-known segmentation techniques. These include straightforward techniques such as Artificial Neural Network and fuzzy C-means as well as more advanced techniques such as the Fuzzy And Noise Tolerant Adaptive Segmentation Method, fMRI of the Brain Automated Segmentation Tool, SPM5, and SPM8. Thirty T1-weighted images from patients with MS from 3 different scanners were segmented twice, first including white matter lesions and then masking the lesions before segmentation and relabeling as WM afterward. The differences in total tissue volume and tissue volume outside the lesion regions were computed between the images by using the 2 methodologies. Total gray matter volume was overestimated by all methods when lesion volume increased. The tissue volume outside the lesion regions was also affected by white matter lesions with differences up to 20 cm(3) on images with a high lesion load (≈50 cm(3)). SPM8 and Fuzzy And Noise Tolerant Adaptive Segmentation Method were the methods less influenced by white matter lesions, whereas the effect of white matter lesions was more prominent on fuzzy C-means and the fMRI of the Brain Automated Segmentation Tool. Although lesions were removed after segmentation to avoid their impact on tissue segmentation, the methods still overestimated GM tissue in most cases. This finding is especially relevant because on images with high lesion load, this bias will most likely distort actual tissue atrophy measurements. © 2015 by American Journal of Neuroradiology.

  15. Investigation of quantitative magnetisation transfer parameters of lesions and normal appearing white matter in multiple sclerosis.

    Science.gov (United States)

    Cercignani, M; Basile, B; Spanò, B; Comanducci, G; Fasano, F; Caltagirone, C; Nocentini, U; Bozzali, M

    2009-07-01

    The aim of this study was to use quantitative magnetisation transfer (MT) imaging to assess the different pathological substrates of tissue damage in multiple sclerosis (MS) and examine whether the MT parameters may be used to explain the disability in relapsing remitting (RR) MS. Thirteen patients with RRMS and 14 healthy controls were prescribed conventional MRI and quantitative MT imaging at 3.0 T. A two-pool model of MT (where A refers to the free pool and B to the macromolecular pool) was fitted to the data yielding a longitudinal relaxation rate R(A), a relative size F of macromolecular pool, transverse relaxation times T(2) (A) and T(2) (B) for the two pools and a forward exchange rate RM(0) (B). The MT ratio (MTR) was also computed. The mean MT parameters of the normal appearing white matter (NAWM) and of lesions in patients, and of white matter in controls were estimated. MT parameters were significantly different between lesions and NAWM in patients, and between the NAWM and the white matter of controls (with the exception of T(2) (B) and the MTR). Two models were investigated using ordered logistic regression, with the expanded disability status scale (EDSS) as the dependent variable. In the first one, mean NAWM MT parameters and lesion load were entered as explanatory variables; in the second one, mean MT variables within lesions and lesion load were entered as explanatory variables. Unexpectedly, T(2) (B) was the parameter most significantly associated with EDSS in NAWM. This parameter might represent a weighted average of the relaxation times of spins with different molecular environments, and therefore its variation could indicate a change in the balance between subpopulations of macromolecular spins. Conversely, in lesions, RM(0) (B), T(2) (B), F, R(A), and lesion load significantly predicted disability only when combined together. This might reflect the complex interaction between demyelination, remyelination, gliosis, inflammation and axonal loss

  16. Age dependent white matter lesions and brain volume changes in healthy volunteers

    DEFF Research Database (Denmark)

    Christiansen, P; Larsson, H B; Thomsen, C

    1994-01-01

    The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles was meas......The brain of 142 healthy volunteers aged 21 to 80 years were investigated using MR imaging. The number and size of the white matter hyperintensity lesions (WMHL) in the cerebral hemispheres were determined. Furthermore, the volume of the cerebral hemispheres and of the lateral ventricles...... was measured. An almost linear increase in the number of volunteers with WMHL was seen with aging for males and females. With aging a significant decrease in the volume of the cerebral hemispheres was found for males, and a significant increase in the volume of the lateral ventricles was seen for both males...... and females. Our results suggest that with aging central atrophy increases more (relatively) than cortical atrophy. No correlation was found between the decreasing volume of the cerebral hemispheres and the increasing number and size of WMHL, nor between the increasing volume of the lateral ventricles...

  17. [Birth weight as predictor for the severity of neonatal brain white matter lesion].

    Science.gov (United States)

    Argollo, Nayara; Lessa, Ines; Ribeiro, Suely; Abreu, Katiusha C; Pinto, Juliana M S; Faria, Raquel P; Telles, Tatiana G; Santos, Gabriel B

    2006-06-01

    To analyze the association of natal factors with the severity of neonatal brain white matter lesion (WML) by controlling the birth weight, we identified newborns with WML who were divided into: those with WML evolution towards resolution of the ultrasound image (less severe), and those who evolved with cist formation and/or ventriculomegalia and/or hemorrhage (greater severity). There were differences among the twelve variables (hyponatremia, anemia, infection, retinopathy, broncopulmonary dysplasia, hypoalbuminemia, persistence of the arterial canal, altered audiometry, early respiratory distress, birth weigh below 2,500 g, weight per category, and prematurity) between the two groups (p<0.05), being that nine variables (hyponatremia, infection, retinopathy, hypoalbuminemia, persistence of the arterial canal, early respiratory distress, low weight, prematurity, and weight per category) remained statistically different (p<0.01) after the logistic regression analysis. When the variables were analyzed by birth weight category none of them presented statistical significance. This study suggests that birth weight is the major factor--likely the only one--associated to the severity of neonatal brain white matter lesion.

  18. Reproducibility of brain metabolite concentration measurements in lesion free white matter at 1.5 T.

    Science.gov (United States)

    Busch, Martin H J; Vollmann, Wolfgang; Mateiescu, Serban; Stolze, Manuel; Deli, Martin; Garmer, Marietta; Grönemeyer, Dietrich H W

    2015-09-29

    Post processing for brain spectra has a great influence on the fit quality of individual spectra, as well as on the reproducibility of results from comparable spectra. This investigation used pairs of spectra, identical in system parameters, position and time assumed to differ only in noise. The metabolite amplitudes of fitted time domain spectroscopic data were tested on reproducibility for the main brain metabolites. Proton spectra of white matter brain tissue were acquired with a short spin echo time of 30 ms and a moderate repetition time of 1500 ms at 1.5 T. The pairs were investigated with one time domain post-processing algorithm using different parameters. The number of metabolites, the use of prior knowledge, base line parameters and common or individual damping were varied to evaluate the best reproducibility. The protocols with most reproducible amplitudes for N-acetylaspartate, creatine, choline, myo-inositol and the combined Glx line of glutamate and glutamine in lesion free white matter have the following common features: common damping of the main metabolites, a baseline using only the points of the first 10 ms, no additional lipid/macromolecule lines and Glx is taken as the sum of separately fitted glutamate and glutamine. This parameter set is different to the one delivering the best individual fit results. All spectra were acquired in "lesion free" (no lesion signs found in MR imaging) white matter. Spectra of brain lesions, for example tumors, can be drastically different. Thus the results are limited to lesion free brain tissue. Nevertheless the application to studies is broad, because small alterations in brain biochemistry of lesion free areas had been detected nearby tumors, in patients with multiple sclerosis, drug abuse or psychiatric disorders. Main metabolite amplitudes inside healthy brain can be quantified with a normalized root mean square deviation around 5 % using CH3 of creatine as reference. Only the reproducibility of myo

  19. Improved Automatic Segmentation of White Matter Hyperintensities in MRI Based on Multilevel Lesion Features.

    Science.gov (United States)

    Rincón, M; Díaz-López, E; Selnes, P; Vegge, K; Altmann, M; Fladby, T; Bjørnerud, A

    2017-07-01

    Brain white matter hyperintensities (WMHs) are linked to increased risk of cerebrovascular and neurodegenerative diseases among the elderly. Consequently, detection and characterization of WMHs are of significant clinical importance. We propose a novel approach for WMH segmentation from multi-contrast MRI where both voxel-based and lesion-based information are used to improve overall performance in both volume-oriented and object-oriented metrics. Our segmentation method (AMOS-2D) consists of four stages following a "generate-and-test" approach: pre-processing, Gaussian white matter (WM) modelling, hierarchical multi-threshold WMH segmentation and object-based WMH filtering using support vector machines. Data from 28 subjects was used in this study covering a wide range of lesion loads. Volumetric T1-weighted images and 2D fluid attenuated inversion recovery (FLAIR) images were used as basis for the WM model and lesion masks defined manually in each subject by experts were used for training and evaluating the proposed method. The method obtained an average agreement (in terms of the Dice similarity coefficient, DSC) with experts equivalent to inter-expert agreement both in terms of WMH number (DSC = 0.637 vs. 0.651) and volume (DSC = 0.743 vs. 0.781). It allowed higher accuracy in detecting WMH compared to alternative methods tested and was further found to be insensitive to WMH lesion burden. Good agreement with expert annotations combined with stable performance largely independent of lesion burden suggests that AMOS-2D will be a valuable tool for fully automated WMH segmentation in patients with cerebrovascular and neurodegenerative pathologies.

  20. Fully automatic detection of deep white matter T1 hypointense lesions in multiple sclerosis

    Science.gov (United States)

    Spies, Lothar; Tewes, Anja; Suppa, Per; Opfer, Roland; Buchert, Ralph; Winkler, Gerhard; Raji, Alaleh

    2013-12-01

    A novel method is presented for fully automatic detection of candidate white matter (WM) T1 hypointense lesions in three-dimensional high-resolution T1-weighted magnetic resonance (MR) images. By definition, T1 hypointense lesions have similar intensity as gray matter (GM) and thus appear darker than surrounding normal WM in T1-weighted images. The novel method uses a standard classification algorithm to partition T1-weighted images into GM, WM and cerebrospinal fluid (CSF). As a consequence, T1 hypointense lesions are assigned an increased GM probability by the standard classification algorithm. The GM component image of a patient is then tested voxel-by-voxel against GM component images of a normative database of healthy individuals. Clusters (≥0.1 ml) of significantly increased GM density within a predefined mask of deep WM are defined as lesions. The performance of the algorithm was assessed on voxel level by a simulation study. A maximum dice similarity coefficient of 60% was found for a typical T1 lesion pattern with contrasts ranging from WM to cortical GM, indicating substantial agreement between ground truth and automatic detection. Retrospective application to 10 patients with multiple sclerosis demonstrated that 93 out of 96 T1 hypointense lesions were detected. On average 3.6 false positive T1 hypointense lesions per patient were found. The novel method is promising to support the detection of hypointense lesions in T1-weighted images which warrants further evaluation in larger patient samples.

  1. White matter lesion segmentation using machine learning and weakly labeled MR images

    Science.gov (United States)

    Xie, Yuchen; Tao, Xiaodong

    2011-03-01

    We propose a fast, learning-based algorithm for segmenting white matter (WM) lesions for magnetic resonance (MR) brain images. The inputs to the algorithm are T1, T2, and FLAIR images. Unlike most of the previously reported learning-based algorithms, which treat expert labeled lesion map as ground truth in the training step, the proposed algorithm only requires the user to provide a few regions of interest (ROI's) containing lesions. An unsupervised clustering algorithm is applied to segment these ROI's into areas. Based on the assumption that lesion voxels have higher intensity on FLAIR image, areas corresponding to lesions are identified and their probability distributions in T1, T2, and FLAIR images are computed. The lesion segmentation in 3D is done by using the probability distributions to generate a confidence map of lesion and applying a graph based segmentation algorithm to label lesion voxels. The initial lesion label is used to further refine the probability distribution estimation for the final lesion segmentation. The advantages of the proposed algorithm are: 1. By using the weak labels, we reduced the dependency of the segmentation performance on the expert discrimination of lesion voxels in the training samples; 2. The training can be done using labels generated by users with only general knowledge of brain anatomy and image characteristics of WM lesion, instead of these carefully labeled by experienced radiologists; 3. The algorithm is fast enough to make interactive segmentation possible. We test the algorithm on nine ACCORD-MIND MRI datasets. Experimental results show that our algorithm agrees well with expert labels and outperforms a support vector machine based WM lesion segmentation algorithm.

  2. Automatic white matter lesion segmentation using an adaptive outlier detection method.

    Science.gov (United States)

    Ong, Kok Haur; Ramachandram, Dhanesh; Mandava, Rajeswari; Shuaib, Ibrahim Lutfi

    2012-07-01

    White matter (WM) lesions are diffuse WM abnormalities that appear as hyperintense (bright) regions in cranial magnetic resonance imaging (MRI). WM lesions are often observed in older populations and are important indicators of stroke, multiple sclerosis, dementia and other brain-related disorders. In this paper, a new automated method for WM lesions segmentation is presented. In the proposed method, the presence of WM lesions is detected as outliers in the intensity distribution of the fluid-attenuated inversion recovery (FLAIR) MR images using an adaptive outlier detection approach. Outliers are detected using a novel adaptive trimmed mean algorithm and box-whisker plot. In addition, pre- and postprocessing steps are implemented to reduce false positives attributed to MRI artifacts commonly observed in FLAIR sequences. The approach is validated using the cranial MRI sequences of 38 subjects. A significant correlation (R=0.9641, P value=3.12×10(-3)) is observed between the automated approach and manual segmentation by radiologist. The accuracy of the proposed approach was further validated by comparing the lesion volumes computed using the automated approach and lesions manually segmented by an expert radiologist. Finally, the proposed approach is compared against leading lesion segmentation algorithms using a benchmark dataset. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Punctate white matter lesions in infants: new insights using susceptibility-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Niwa, Tetsu [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Kanagawa Children' s Medical Center, Departments of Radiology, Yokohama (Japan); Vries, Linda S. de; Benders, Manon J.N.L.; Groenendaal, Floris [Wilhelmina Children' s Hospital/University Medical Center Utrecht, Department of Neonatology, KE 04.123.1, PO Box 85090, Utrecht (Netherlands); Takahara, Taro [University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands); Nikkels, Peter G.J. [University Medical Center Utrecht, Department of Pathology, Heidelberglaan 100, PO Box 85500, Utrecht (Netherlands)

    2011-09-15

    Punctate white matter lesions (PWML) are recognized with magnetic resonance imaging (MRI) as hypersignal on T1-weighted imaging and hyposignal on T2-weighted imaging. Our aim was to assess how often a hemorrhagic component was present in PWML using susceptibility-weighted imaging (SWI). Seventeen preterm (gestational age, 25-34 weeks) and seven full-term infants (age at MRI, 37-42 weeks) with PWML were included. Seven preterm infants had sequential MRIs. PWML were diagnosed with conventional MRI and compared with SWI, where signal loss is suggestive of hemorrhage. The pattern of associated brain lesions was taken into account, and the percentage of lesions with signal loss on SWI was calculated for each infant. A significantly higher percentage of signal loss on SWI (median, 93.9%) was found among infants with germinal matrix and intraventricular hemorrhage as the primary diagnosis (n = 8) compared to those with a primary diagnosis of white matter injury (n = 14; median, 14.2%; p < 0.01). In the infants with serial MRIs, a reduction in the number of PWML and/or signal loss on SWI was noted at term equivalent age. In the patient who died, cystic lesions, associated with hemorrhage and gliosis, were demonstrated on histology. SWI can distinguish hemorrhagic and non-hemorrhagic PWML. Signal loss on SWI was more common when PWML were associated with an intraventricular hemorrhage. Longitudinal imaging showed a decrease in the number of PWML over time, with some PWML no longer showing signal loss on SWI, suggesting early gliosis. (orig.)

  4. Limitations on the Developing Preterm Brain: Impact of Periventricular White Matter Lesions on Brain Connectivity and Cognition

    Science.gov (United States)

    Pavlova, Marina A.; Krageloh-Mann, Ingeborg

    2013-01-01

    Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…

  5. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K.; Yamadori, A. [Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575 Sendai (Japan); Constans, J.M.; Courtheoux, P.; Theron, J. [MR Unit, University of Caen School of Medicine, Caen (France); Viader, F. [Department of Neuroradiology, University of Caen School of Medicine, Caen (France)

    2000-06-01

    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  6. White Matter MS-Lesion Segmentation Using a Geometric Brain Model.

    Science.gov (United States)

    Strumia, Maddalena; Schmidt, Frank R; Anastasopoulos, Constantinos; Granziera, Cristina; Krueger, Gunnar; Brox, Thomas

    2016-07-01

    Brain magnetic resonance imaging (MRI) in patients with Multiple Sclerosis (MS) shows regions of signal abnormalities, named plaques or lesions. The spatial lesion distribution plays a major role for MS diagnosis. In this paper we present a 3D MS-lesion segmentation method based on an adaptive geometric brain model. We model the topological properties of the lesions and brain tissues in order to constrain the lesion segmentation to the white matter. As a result, the method is independent of an MRI atlas. We tested our method on the MICCAI MS grand challenge proposed in 2008 and achieved competitive results. In addition, we used an in-house dataset of 15 MS patients, for which we achieved best results in most distances in comparison to atlas based methods. Besides classical segmentation distances, we motivate and formulate a new distance to evaluate the quality of the lesion segmentation, while being robust with respect to minor inconsistencies at the boundary level of the ground truth annotation.

  7. The effect of hypointense white matter lesions on automated gray matter segmentation in multiple sclerosis.

    Science.gov (United States)

    Gelineau-Morel, Rose; Tomassini, Valentina; Jenkinson, Mark; Johansen-Berg, Heidi; Matthews, Paul M; Palace, Jacqueline

    2012-12-01

    Previous imaging studies assessing the relationship between white matter (WM) damage and matter (GM) atrophy have raised the concern that Multiple Sclerosis (MS) WM lesions may affect measures of GM volume by inducing voxel misclassification during intensity-based tissue segmentation. Here, we quantified this misclassification error in simulated and real MS brains using a lesion-filling method. Using this method, we also corrected GM measures in patients before comparing them with controls in order to assess the impact of this lesion-induced misclassification error in clinical studies. We found that higher WM lesion volumes artificially reduced total GM volumes. In patients, this effect was about 72% of that predicted by simulation. Misclassified voxels were located at the GM/WM border and could be distant from lesions. Volume of individual deep gray matter (DGM) structures generally decreased with higher lesion volumes, consistent with results from total GM. While preserving differences in GM volumes between patients and controls, lesion-filling correction revealed more lateralised DGM shape changes in patients, which were not evident with the original images. Our results confirm that WM lesions can influence MRI measures of GM volume and shape in MS patients through their effect on intensity-based GM segmentation. The greater effect of lesions at increasing levels of damage supports the use of lesion-filling to correct for this problem and improve the interpretability of the results. Volumetric or morphometric imaging studies, where lesion amount and characteristics may vary between groups of patients or change over time, may especially benefit from this correction. Copyright © 2011 Wiley Periodicals, Inc.

  8. Evaluating and reducing the impact of white matter lesions on brain volume measurements.

    Science.gov (United States)

    Battaglini, Marco; Jenkinson, Mark; De Stefano, Nicola

    2012-09-01

    MR-based measurements of brain volumes may be affected by the presence of white matter (WM) lesions. Here, we assessed how and to what extent this may happen for WM lesions of various sizes and intensities. After inserting WM lesions of different sizes and intensities into T1-W brain images of healthy subjects, we assessed the effect on two widely used automatic methods for brain volume measurement such as SIENAX (segmentation-based) and SIENA (registration-based). To explore the relevance of partial volume (PV) estimation, we performed the experiments with two different PV models, implemented by the same segmentation algorithm (FAST) of SIENAX and SIENA. Finally, we tested potential solutions to this issue. The presence of WM lesions did not bias measurements for registration-based method such as SIENA. By contrast, the presence of WM lesions affected segmentation-based brain volume measurements such as SIENAx. The misclassification of both gray matter (GM) and WM volumes varied considerably with lesion size and intensity, especially when the lesion intensity was similar to that of the GM/WM interface. The extent to which the presence of WM lesions could affect tissue-class measures was clearly driven by the PV modeling used, with the mixel-type PV model giving a lower error in the presence of WM lesions. The tissue misclassification due to WM lesions was still present when they were masked out. By contrast, refilling the lesions with intensities matching the surrounding normal-appearing WM ensured accurate tissue-class measurements and thus represents a promising approach for accurate tissue classification and brain volume measurements. Copyright © 2011 Wiley Periodicals, Inc.

  9. Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study

    Science.gov (United States)

    O’Brien, John; Ames, David; Chiu, Edmond; Schweitzer, Isaac; Desmond, Patricia; Tress, Brian

    1998-01-01

    Objective To determine the difference in outcome among elderly people with major depression who do and do not have severe white matter lesions on magnetic resonance imaging. Design Follow up study. Setting Two psychiatric and two general hospitals in Melbourne, Australia. Subjects 60 depressed subjects aged over 55 referred to hospital psychiatric services with major depressive disorder meeting American Psychiatric Association (DSM-IIIR) criteria. Main outcome measure Proportion with good outcome as determined by full recovery from initial illness and no evidence of depressive relapse or cognitive decline during follow up among those with and without lesions. Results Mean (SD) follow up was 31.9 (9.9) months. Survival analysis showed a significant effect of severe lesions on time to poor outcome (P=0.04), with median survival 136 days in those with severe lesions compared with 315 days in those without. Conclusion Severe white matter change on magnetic resonance imaging is associated with poor outcome in elderly depressed subjects. Key messagesSevere deep white matter lesions on magnetic resonance imaging are common in elderly patients with depressionPatients with these lesions are at greater risk of poor long term outcome (chronicity and relapse) than those without lesionsThe neuropathogical and neurochemical correlates of these white matter changes need investigation PMID:9765166

  10. The impact of subcortical white matter disease on mood in euthymic older adults: a diffusion tensor imaging study.

    Science.gov (United States)

    Lamar, Melissa; Charlton, Rebecca A; Morris, Robin G; Markus, Hugh S

    2010-07-01

    Clinical depression in the elderly is associated with cerebral small vessel disease. It is less certain whether the endorsement of depressive symptoms in the absence of clinical depression, relatively common in euthymic older adults, is also associated with white matter damage. The majority of studies exploring this issue have produced mixed results, perhaps due, in part, to differences in defining the threshold for depression, notating vascular risk factors, and/or the neuroimaging tools used to quantify white matter damage. We aimed to address these issues with non-demented euthymic older adults. We performed diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) in a population based cohort of 79 individuals (mean age = 68 years). In addition to neuroimaging, the authors report assessments of overall cognition, executive functioning, and depression. Scores on the Geriatric Depression Scale 15-item (GDS-15) correlated with DTI measures of mean diffusivity (r [77] = 0.23, p = 0.039) and fractional anisotropy (r [77] = -0.22, p = 0.045) but only approached significance for T2-weighted MRI measures of white matter hyperintensities (WMH; r [77] = 0.21, p = 0.053). After adjusting for factors known to influence the development of WMH and depression, including age and vascular risks, DTI-derived indices of white matter integrity remained significantly associated with GDS-15 scores. Furthermore, only DTI-derived measures of white matter integrity contributed to the variance in GDS-15 scores in logistical regression modeling. These findings demonstrate an association between white matter damage and the endorsement of depressive symptoms in euthymic older adults and suggest that DTI may be more sensitive to this damage than T2-WMH in an aging cohort with multiple vascular risk factors.

  11. Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation: laboratory investigation.

    Science.gov (United States)

    De Benedictis, Alessandro; Sarubbo, Silvio; Duffau, Hugues

    2012-12-01

    Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

  12. Comparing Cerebral White Matter Lesion Burdens between Parkinson’s Disease with and without Dementia

    Science.gov (United States)

    Choi, Sun-Ah; Evidente, Virgilio Gerald H.; Caviness, John N

    2010-01-01

    Cerebral white matter lesions (CWMLs) have been suggested to be associated with an increased risk of dementia, disability, and death. CWMLs are more common in individuals with Alzheimer’s disease (AD) than in normal elderly individuals of comparable age. Only a few studies have been done to determine whether CWMLs may influence cognitive decline in Parkinson’s disease (PD). Fully developed PD with concurrent AD was reported to likely cause impaired cognition in spite of accumulating evidence suggesting that PD with dementia (PDD) is more closely associated with Lewy body (LB) pathology. Currently, contradictory data on the neuropathology of dementia in PD require further prospective clinicopathological studies in larger cohorts to elucidate the impact of AD and α-synuclein (SCNA) pathologies on the cognitive status in these disorders. Previous reports did not suggest CWMLs to be associated with an increased risk of PDD. After adjusting for age at death, age at onset of PD, and duration of PD, our recent study investigating CWMLs in PDD via autopsy has shown a positive correlation between the burden of CWMLs and PDD. The frequent co-existence of both LB and AD lesions suggests that both pathologies independently or synergistically contribute to both movement disorders and cognitive impairment. The individual and cumulative burden of CWMLs, LB lesions, and AD lesions may synergistically contribute to cognitive decline in LB disorders such as PDD. PMID:24868371

  13. Comparing Cerebral White Matter Lesion Burdens between Parkinson’s Disease with and without Dementia

    Directory of Open Access Journals (Sweden)

    Sun-Ah Choi

    2010-05-01

    Full Text Available Cerebral white matter lesions (CWMLs have been suggested to be associated with an increased risk of dementia, disability, and death. CWMLs are more common in individuals with Alzheimer’s disease (AD than in normal elderly individuals of comparable age. Only a few studies have been done to determine whether CWMLs may influence cognitive decline in Parkinson’s disease (PD. Fully developed PD with concurrent AD was reported to likely cause impaired cognition in spite of accumulating evidence suggesting that PD with dementia (PDD is more closely associated with Lewy body (LB pathology. Currently, contradictory data on the neuropathology of dementia in PD require further prospective clinicopathological studies in larger cohorts to elucidate the impact of AD and α-synuclein (SCNA pathologies on the cognitive status in these disorders. Previous reports did not suggest CWMLs to be associated with an increased risk of PDD. After adjusting for age at death, age at onset of PD, and duration of PD, our recent study investigating CWMLs in PDD via autopsy has shown a positive correlation between the burden of CWMLs and PDD. The frequent co-existence of both LB and AD lesions suggests that both pathologies independently or synergistically contribute to both movement disorders and cognitive impairment. The individual and cumulative burden of CWMLs, LB lesions, and AD lesions may synergistically contribute to cognitive decline in LB disorders such as PDD.

  14. Automated tissue segmentation of MR brain images in the presence of white matter lesions.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; González-Villà, Sandra; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Rovira, Àlex; Lladó, Xavier

    2017-01-01

    Over the last few years, the increasing interest in brain tissue volume measurements on clinical settings has led to the development of a wide number of automated tissue segmentation methods. However, white matter lesions are known to reduce the performance of automated tissue segmentation methods, which requires manual annotation of the lesions and refilling them before segmentation, which is tedious and time-consuming. Here, we propose a new, fully automated T1-w/FLAIR tissue segmentation approach designed to deal with images in the presence of WM lesions. This approach integrates a robust partial volume tissue segmentation with WM outlier rejection and filling, combining intensity and probabilistic and morphological prior maps. We evaluate the performance of this method on the MRBrainS13 tissue segmentation challenge database, which contains images with vascular WM lesions, and also on a set of Multiple Sclerosis (MS) patient images. On both databases, we validate the performance of our method with other state-of-the-art techniques. On the MRBrainS13 data, the presented approach was at the time of submission the best ranked unsupervised intensity model method of the challenge (7th position) and clearly outperformed the other unsupervised pipelines such as FAST and SPM12. On MS data, the differences in tissue segmentation between the images segmented with our method and the same images where manual expert annotations were used to refill lesions on T1-w images before segmentation were lower or similar to the best state-of-the-art pipeline incorporating automated lesion segmentation and filling. Our results show that the proposed pipeline achieved very competitive results on both vascular and MS lesions. A public version of this approach is available to download for the neuro-imaging community. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Stratified mixture modeling for segmentation of white-matter lesions in brain MR images.

    Science.gov (United States)

    Galimzianova, Alfiia; Pernuš, Franjo; Likar, Boštjan; Špiclin, Žiga

    2016-01-01

    Accurate characterization of white-matter lesions from magnetic resonance (MR) images has increasing importance for diagnosis and management of treatment of certain neurological diseases, and can be performed in an objective and effective way by automated lesion segmentation. This usually involves modeling the whole-brain MR intensity distribution, however, capturing various sources of MR intensity variability and lesion heterogeneity results in highly complex whole-brain MR intensity models, thus their robust estimation on a large set of MR images presents a huge challenge. We propose a novel approach employing stratified mixture modeling, where the main premise is that the otherwise complex whole-brain model can be reduced to a tractable parametric form in small brain subregions. We show on MR images of multiple sclerosis (MS) patients with different lesion loads that robust estimators enable accurate mixture modeling of MR intensity in small brain subregions even in the presence of lesions. Recombination of the mixture models across strata provided an accurate whole-brain MR intensity model. Increasing the number of subregions and, thereby, the model complexity, consistently improved the accuracy of whole-brain MR intensity modeling and segmentation of normal structures. The proposed approach was incorporated into three unsupervised lesion segmentation methods and, compared to original and three other state-of-the-art methods, the proposed modeling approach significantly improved lesion segmentation according to increased Dice similarity indices and lower number of false positives on real MR images of 30 patients with MS. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

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

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Lladó, Xavier

    2014-01-01

    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.

  18. Accurate white matter lesion segmentation by k nearest neighbor classification with tissue type priors (kNN-TTPs)

    NARCIS (Netherlands)

    Steenwijk, M.D.; Pouwels, P.J.; Daams, M.; van Dalen, J.W.; Caan, M.W.; Richard, E.; Barkhof, F.; Vrenken, H.

    2013-01-01

    Introduction The segmentation and volumetric quantification of white matter (WM) lesions play an important role in monitoring and studying neurological diseases such as multiple sclerosis (MS) or cerebrovascular disease. This is often interactively done using 2D magnetic resonance images. Recent

  19. Hereditary motor and sensory neuropathy with hypertrophy of the cauda equina and concomitant demyelinating white matter lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ertl-Wagner, B.B.; Staebler, A.; Reiser, M. [Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie; Helmchen, C. [Univ. Luebeck (Germany). Klinik fuer Neurologie; Fassmann, F. [Zentrum fuer Radiologie und Nuklearmedizin, Erlangen-Nuernberg (Germany)

    2005-07-01

    Hereditary motor and sensory neuropathy (HMSN) is thought to almost exclusively affect the peripheral nervous system. We report the case of a 48-year-old patient with a longstanding history of HMSN type I who developed signs and symptoms of a cauda equina compression and of a central nervous system relapsing-remitting demyelinating white matter disease. Gross enlargement of the cauda equina fibers was detected by MR imaging of the lumbar spine. Cranial MR imaging revealed demyelinating white matter lesions. This case suggests that peripheral neuropathic mechanisms may also affect the central myelin in HMSN type I.

  20. Influence of cerebral white matter lesions on the activities of daily living of older patients with mild stroke.

    Science.gov (United States)

    Yamashita, Yutaka; Wada, Ikuo; Horiba, Mitsuya; Sahashi, Kento

    2016-08-01

    Neurological symptom severity is a prognostic factor for post-stroke activities of daily living (ADL). Recently, it has been reported that white matter lesions indicate poor functional prognosis in patients with stroke. The present study investigated the influence of white matter lesions on the ADL of older patients with stroke who have mild neurological symptoms. We investigated ADL at discharge in 44 patients with stroke (men, n = 27; women, n = 17; mean age 78 years [range 71-85 years]) aged ≥65 years with National Institutes of Health Stroke Scale scores of ≤5 (cerebral infarction, n = 37; cerebral hemorrhage, n = 7). We used single correlation analysis and multiple regression analysis to investigate factors that correlated with ADL at discharge. ADL at discharge was also evaluated on the basis of white matter lesion severity (Fazekas classification, grades 0-3). Single correlation analysis showed that age (r = -0.36, P = 0.016), male sex (r = 0.362, P = 0.016), neurological symptom severity (r = -0.361, P = 0.016), ADL on starting rehabilitation (r = 0.685, P < 0.001) and white matter lesion severity (r = -0.361, P = 0.016) significantly correlated with ADL at discharge. Multiple regression analysis showed that ADL on starting rehabilitation (β = 0.519, t = 4.723, P < 0.001) and white matter lesion severity (β = -0.309, t = -3.057, P < 0.01) were statistically significant prognostic factors for ADL at discharge. ADL at discharge score was significantly lower in the group with high white matter lesion severity (Fazekas, grade 2) than in the other two groups (Fazekas, grade 0, P < 0.01; Fazekas, grade 1, P < 0.05). Severe white matter lesions are a prognostic factor for poor ADL at discharge in older patients with stroke who have mild neurological symptoms. Geriatr Gerontol Int 2016; 16: 942-947. © 2015 Japan Geriatrics Society.

  1. Impact of white matter lesions and cognitive deficits on conversion from mild cognitive impairment to Alzheimer's disease.

    Science.gov (United States)

    Defrancesco, Michaela; Marksteiner, Josef; Deisenhammer, Eberhard; Kemmler, Georg; Djurdjevic, Tanja; Schocke, Michael

    2013-01-01

    Mild cognitive impairment (MCI) may represent a prodromal stage of dementia and confers a particularly high annual risk of 10-15% for conversion to Alzheimer's disease (AD). Recent findings suggest that white matter lesion pathology (WML) can negatively influence conversion from MCI to AD. In this study, we examined the predictive value of neuropsychological test results and WML pathology on conversion of MCI to AD. Retrospective neuropsychological and magnetic resonance imaging data were collected for MCI patients seen at the University Clinic of Innsbruck between 2005 and 2011. WML were visually rated using the Fazekas and Scheltens scales. Of the 60 subjects, 31 converted to AD during a follow-up of 18.3 ± 7.4 months and 29 remained stable. Orientation, MMSE score, word list learning and recall, visual memory, and naming scores were significantly lower in MCI patients converting to AD than in non-converters. Converters had significantly higher Fazekas scores and more WML in periventricular regions. Periventricular WML were negatively associated with psychomotor speed, and subcortical WML were negatively correlated with visual memory at baseline in all MCI patients. Low scores in orientation and verbal delayed recall were predictors of progression from MCI to AD. Periventricular WML correlate with lower cognitive function in patients with MCI. However, deficits in orientation and verbal memory, but not vascular changes, turned out as predictive for conversion from MCI to AD. Consequently, a higher WML burden may represent a serious risk factor but not an early symptom for the imminent conversion to AD.

  2. Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions.

    Science.gov (United States)

    Nijland, Philip G; Michailidou, Iliana; Witte, Maarten E; Mizee, Mark R; van der Pol, Susanne M A; van Het Hof, Bert; Reijerkerk, Arie; Pellerin, Luc; van der Valk, Paul; de Vries, Helga E; van Horssen, Jack

    2014-07-01

    To ensure efficient energy supply to the high demanding brain, nutrients are transported into brain cells via specific glucose (GLUT) and monocarboxylate transporters (MCT). Mitochondrial dysfunction and altered glucose metabolism are thought to play an important role in the progression of neurodegenerative diseases, including multiple sclerosis (MS). Here, we investigated the cellular localization of key GLUT and MCT proteins in human brain tissue of non-neurological controls and MS patients. We show that in control brain tissue GLUT and MCT proteins were abundantly expressed in a variety of central nervous system cells, particularly in microglia and endothelial cells. In active MS lesions, GLUTs and MCTs were highly expressed in infiltrating leukocytes and reactive astrocytes. Astrocytes manifest increased MCT1 staining and maintain GLUT expression in inactive lesions, whereas demyelinated axons exhibit significantly reduced GLUT3 and MCT2 immunoreactivity in inactive lesions. Finally, we demonstrated that the co-transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α), an important protein involved in energy metabolism, is highly expressed in reactive astrocytes in active MS lesions. Overexpression of PGC-1α in astrocyte-like cells resulted in increased production of several GLUT and MCT proteins. In conclusion, we provide for the first time a comprehensive overview of key nutrient transporters in white matter brain samples. Moreover, our data demonstrate an altered expression of these nutrient transporters in MS brain tissue, including a marked reduction of axonal GLUT3 and MCT2 expression in chronic lesions, which may impede efficient nutrient supply to the hypoxic demyelinated axons thereby contributing to the ongoing neurodegeneration in MS. Copyright © 2014 Wiley Periodicals, Inc.

  3. Early-stage white matter lesions detected by multispectral MRI segmentation predict progressive cognitive decline

    Directory of Open Access Journals (Sweden)

    Hanna eJokinen

    2015-12-01

    Full Text Available White matter lesions (WML are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a pre-visible stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%, intermediate (66%, or high (100% proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment.

  4. Subcortical frontal lesions on MRI in patients with motor neurone disease

    Energy Technology Data Exchange (ETDEWEB)

    Andreadou, E.; Sgouropoulos, P.; Varelas, P.; Papageorgiou, C. [Eginition Hospital, Athens (Greece); Gouliamos, A. [Department of Radiology, CT/MRI Unit, Areteion Hospital, University of Athens (Greece)

    1998-05-01

    MRI was performed in 32 patients with motor neurone disease (26 men and 6 women, aged 40-77 years) and in a control group of 21 subjects. Of the patients studied, 19 had definite and 11 probable amyotrophic lateral sclerosis (ALS) and two had progressive bulbar palsy. In 10 patients there were asymmetrical bilateral foci of increased signal intensity on proton-density and T{sub 2}-weighted images, confined to the white matter. Two patients had only cortical frontal atrophy and slightly increased ventricular size, whereas 20 had normal MRI. The focal lesions were not confined to corticospinal tracts, but were also observed in subcortical frontal areas. While the lesions along the corticospinal tracts correspond to pyramidal tract degeneration, the subcortical foci correlate with degeneration of the frontal bundles and indicate generalised involvement of the central nervous system. (orig.) With 3 figs., 2 tabs., 25 refs.

  5. Serum Ionized Calcium May Be Related to White Matter Lesion Volumes in Older Adults: A Pilot Study

    Directory of Open Access Journals (Sweden)

    John J. B. Anderson

    2013-06-01

    Full Text Available White matter lesions have detrimental effects upon older adults, while serum calcium levels have been associated with elevated vascular risk and may be associated with these lesions. Depression, a serious mental disorder characterized by disturbances in calcium metabolism, may be an important contributor to any calcium-lesion relationship. This cross-sectional pilot study examined the association between serum ionized calcium (the physiologically active form of calcium and white matter lesion volumes in a sample of depressed and non-depressed older adults (N = 42; 60 years and older. Serum ionized calcium was determined using an ion-selective electrode technique, while lesion volumes were estimated from magnetic resonance imaging using an automated expectation-maximization segmentation. A linear regression model, controlling for age and group (depression vs. comparison, showed a trend for a positive relationship between serum ionized calcium and white matter lesion volume (β = 4.34, SE = 2.27, t = 1.91, p = 0.063. Subsample analyses with depressed participants showed a significant positive relationship between higher ionic calcium and greater lesion volume (β = 6.41, SE = 2.53, t = 2.53, p = 0.018, but no association was found for non-depressed participants. Sex-specific subsample analyses showed a significant positive relationship between higher calcium and greater lesion volume in men only (β = 7.49, SE = 3.42, t = 2.19, p = 0.041. These preliminary results indicate that serum ionized calcium may be associated with white matter lesions in older adults, particularly among men and individuals with depression. Larger studies are needed to confirm these findings.

  6. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

    Directory of Open Access Journals (Sweden)

    Christiane Schneider-Gold

    Full Text Available Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2. We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM.12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.Clinical symptoms were depression (more pronounced in DM2, excessive daytime sleepiness (more pronounced in DM1, reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment

  7. HAM/TSP: association between white matter lesions on magnetic resonance imaging, clinical and cerebrospinal fluid findings

    Directory of Open Access Journals (Sweden)

    Marzia Puccioni-Sohler

    2012-04-01

    Full Text Available OBJECTIVE: To investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (CSF findings in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP. METHOD: We studied brain and cervical spinal cord on magnetic resonance imaging (MRI and CSF examinations of 28 Brazilian HAM/TSP patients. RESULTS: The majority of patients had severe neurological incapacity with EDSS median of 6.5 (3-8. The brain MRI showed white matter lesions (75% and atrophy (14%. The preferential brain location was periventricular. Cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. One patient had enhancement lesions on T1 cervical spinal cord MRI. Cases with spinal cord lesions had signs of acute CSF inflammation. The brain white matter lesions predominated in the patients with higher age. CONCLUSION: Our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in HAM/TSP. The brain abnormalities are not related to the clinical picture of HAM/TSP.

  8. Miller-Fisher syndrome associated with unilateral cerebral white matter lesions.

    Science.gov (United States)

    Xu, Yongfeng; Liu, Lan

    2015-01-01

    Miller-Fisher syndrome (MFS) is characterized by classical triad of ophthalmoplegia, ataxia and areflexia. The involvement of cerebral white matter in MFS is very rare. We report a typical MFS patient whose brain MRI showed unilateral and extensive involvement in cerebral white matter. We also found mild pleocytosis and raised protein concentration in cerebrospinal fluid. Deficits resolved completely after treatment with intravenous immunoglobulins. Subsequent brain MRI shows cavity formation in involved white matter. Copyright © 2015 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Head size may modify the impact of white matter lesions on dementia.

    Science.gov (United States)

    Skoog, Ingmar; Olesen, Pernille J; Blennow, Kaj; Palmertz, Bo; Johnson, Sterling C; Bigler, Erin D

    2012-07-01

    We aimed to examine whether total intracranial volume (TICV), a marker of premorbid brain size, modified the impact of the apolipoprotein E (apoE) e4 phenotype and ischemic white matter lesions (WMLs) on odds for dementia. The study comprised a population-based sample of 104 demented and 135 nondemented 85-year-olds, and included physical and neuropsychiatric examinations, and head computerized tomography (CT). Dementia disorders were defined according to standard criteria. TICV and WMLs were rated on computerized tomography. Using the highest group as reference, the risk for dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was increased in those with the smallest half, tertile, and quartile of TICV. Smaller TICV increased the odds of dementia, Alzheimer's disease, and vascular dementia in participants with WMLs. WMLs were not associated with increased odds of dementia in those with the largest TICV. The interaction term WMLs*TICV was also significant. TICV did not modify the odds of dementia in those with the apolipoprotein e4 phenotype. Our results suggest that the impact of brain pathology on the risk of dementia is modified by premorbid brain size. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Pupillographic Sleepiness Test and Polysomnography in Nondemented Patients with Ischemic White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Ralf Landwehr

    2015-01-01

    Full Text Available Background. Patients with ischemic white matter lesions (WML frequently report nonrestorative sleep or daytime sleepiness. However, subjective estimations of sleep and sleepiness can differ considerably from objective measures. The pupillographic sleepiness test (PST could identify patients with sleep disorders requiring polysomnography (PSG and further treatment. Methods. We performed a PST and a PSG of 35 nondemented patients with WML, who reported nonrestorative sleep or daytime sleepiness, and assessed the diagnostic value of the pupillary unrest index (PUI. Sleep parameters were compared to normative data. Results. The mean PUI of WML patients was normal (5.89 mm/min and comparable to PUIs of patients with other neurological disorders. All 9 of the 35 WML patients (25.7% who had a PUI above normal also had clinically relevant sleep disorders (5: sleep apnea, 7: periodic leg movements, and 4: insomnia. Six patients with a normal PUI had mild to moderate primary insomnia. Conclusion. PST and PSG parameters were physiological in most patients with WML. Age-related changes and affective and neuropsychological disorders might account for their sleep-related complaints. An elevated PUI in patients with WML seems to indicate comorbid sleep disorders that require further diagnostic evaluation and treatment (sleep apnea, insomnia with periodic leg movements, but not primary insomnia.

  11. White matter lesions and vascular vertigo: clinical correlation and findings on cranial magnetic resonance imaging.

    Science.gov (United States)

    Gamba, P; Pavia, M

    2016-07-01

    Vestibular disorders and anxiety are closely related, probably because they share some neuronal pathways. Ageing and patient comorbidities are important facilitating factors, and multiple vascular risk factors could contribute to the onset of a vestibular syndrome called vascular vertigo. White matter lesions (WMLs) are often seen on magnetic resonance imaging (MRI) scans of elderly people and are related to various geriatric disorders, including dizziness. The cause of this correlation could be the disruption of neuronal networks that mediate higher vestibular cortical function. Numerous neuronal pathways link the vestibular network with limbic structures and the prefrontal cortex modulates anxiety through its connections to the amygdala. These could also explain nausea and sickness. The aim of the present work was to investigate the correlation between WML, vascular vertigo and cognitive functions. Our team at the Poliambulanza Foundation Hospital of Brescia studied 90 patients (mean age 75 years) suffering from vascular vertigo with positive WML on MRI, by mapping the lesions and by grading anxiety and sickness symptoms. Furthermore, the same patients were treated with sulodexide (a glycosaminoglycan with antithrombotic activity) for 90 days (500 LSU/day for the first 45 days and 250 LSU/day for the following 45 days) to evaluate the efficacy on the vestibular symptoms. The results showed that the most frequent WML sites were frontal (n=34) and capsule (n=30) areas. Patients had a significant improvement on anxiety and sickness scores (p=0.0001 and p=0.02 respectively) after sulodexide treatment. In patients with vascular vertigo we confirmed the correlation between dizziness and anxiety and showed preliminary data regarding the efficacy of sulodexide in relieving in these patients anxiety and sickness.

  12. Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

    Energy Technology Data Exchange (ETDEWEB)

    Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

    2008-06-15

    We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

  13. A Prospective Pilot Investigation of Brain Volume, White Matter Hyperintensities, and Hemorrhagic Lesions after Mild Traumatic Brain Injury

    OpenAIRE

    Michael eJarrett; Roger eTam; Enedino eHernández-Torres; Nancy eMartin; Warren ePerera; Yinshan eZhao; Elham eShahinfard; Shiroy eDadachanji; Jack eTaunton; David K B Li; Alexander eRauscher

    2016-01-01

    Traumatic brain injury (TBI) is among the most common neurological disorders. Hemorrhagic lesions and white matter hyperintensities (WMH) are radiological features associated with moderate and severe TBI. Brain volume reductions have also been observed during the months following injury. In concussion, no signs of injury are observed on conventional magnetic resonance imaging (MRI), which may be a true feature of concussion or merely due to the limited sensitivity of imaging techniques used s...

  14. Correlation between white matter damage and gray matter lesions in multiple sclerosis patients.

    Science.gov (United States)

    Han, Xue-Mei; Tian, Hong-Ji; Han, Zheng; Zhang, Ce; Liu, Ying; Gu, Jie-Bing; Bakshi, Rohit; Cao, Xia

    2017-05-01

    We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri), right parietal lobe (postcentral and inferior parietal gyri), right temporal lobe (caudate nucleus), right occipital lobe (middle occipital gyrus), right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

  15. Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study

    Directory of Open Access Journals (Sweden)

    Christiane Möller

    2015-01-01

    Full Text Available We investigated the ability of cortical and subcortical gray matter (GM atrophy in combination with white matter (WM integrity to distinguish behavioral variant frontotemporal dementia (bvFTD from Alzheimer's disease (AD and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA and higher mean (MD, axial (L1 and radial diffusivity (L23 values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97–100% of controls, 81–100% of AD and 67–75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.

  16. Magnetic resonance imaging assessment of brain maturation in preterm neonates with punctate white matter lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ramenghi, Luca A.; Fumagalli, Monica; Bassi, Laura; Groppo, Michela; Mosca, Fabio [University of Milan, Neonatal Intensive Care Unit - Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, IRCCS, Milan (Italy); Righini, Andrea; Parazzini, Cecilia; Bianchini, Elena; Triulzi, Fabio [Ospedale Pediatrico ' ' Buzzi' ' -ICP, Department of Radiology and Neuroradiology, Milan (Italy)

    2007-02-15

    Early white matter (WM) injury affects brain maturation in preterm infants as revealed by diffusion tensor imaging and volumetric magnetic resonance (MR) imaging at term postmenstrual age (PMA). The aim of the study was to assess quantitatively brain maturation in preterm infants with and without milder forms of WM damage (punctate WM lesions, PWML) using conventional MRI. Brain development was quantitatively assessed using a previously validated scoring system (total maturation score, TMS) which utilizes four parameters (progressive myelination and cortical infolding, progressive involution of glial cell migration bands and germinal matrix tissue). PWML were defined as foci of increased signal on T1-weighted images and decreased signal on T2-weighted images with no evidence of cystic degeneration. A group of 22 preterm infants with PWML at term PMA (PWML group) were compared with 22 matched controls with a normal MR appearance. The two groups were comparable concerning gestational age, birth weight and PMA. TMS was significantly lower in the PWML group than in the control group (mean TMS 12.44 {+-} 2.31 vs 14.00 {+-} 1.44; P = 0.011). Myelination (mean 2.76 {+-} 0.42 PWML group vs 3.32 {+-} 0.55 control group, P = 0.003) and cortical folding (3.64 {+-} 0.79 vs 4.09 {+-} 0.43, P = 0.027) appeared to be significantly delayed in babies with PWML. Conventional MRI appears able to quantify morphological changes in brain maturation of preterm babies with PWML; delayed myelination and reduced cortical infolding seem to be the most significant aspects. (orig.)

  17. High blood pressure and cerebral white matter lesion progression in the general population.

    Science.gov (United States)

    Verhaaren, Benjamin F J; Vernooij, Meike W; de Boer, Renske; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Ikram, M Arfan

    2013-06-01

    High blood pressure is considered an important risk factor for cerebral white matter lesions (WMLs) in the aging population. In a longitudinal population-based study of 665 nondemented persons, we investigated the longitudinal relationship of systolic blood pressure, diastolic blood pressure, and pulse pressure with annual progression of WMLs. Means of blood pressure were calculated over a 5-year period before longitudinal MRI scanning. WML progression was subsequently measured on 2 scans 3.5 years apart. We performed analyses with linear regression models and evaluated adjustments for age, sex, cardiovascular risk factors, and baseline WML volume. In addition, we evaluated whether treatment of hypertension is related to less WML progression. Both systolic and diastolic blood pressures were significantly associated with annual WML progression (regression coefficient [95% confidence interval], 0.08 [0.03; 0.14] mL/y and 0.09 [0.03; 0.15] mL/y per SD increase in systolic and diastolic blood pressure, respectively). Pulse pressure was also significantly associated with WML progression, but not independent from hypertension. After adjustment for baseline WML volume, only systolic blood pressure remained significantly associated: 0.05 (0.00; 0.09) mL/y per SD increase. People with uncontrolled untreated hypertension had significantly more WML progression than people with uncontrolled treated hypertension (difference [95% confidence interval], 0.12 [0.00; 0.23] mL/y). The present study further establishes high blood pressure to precede WMLs and implies that hypertension treatment could reduce WML progression in the general population.

  18. Preoperative White Matter Lesions Are Independent Predictors of Long-Term Survival after Internal Carotid Endarterectomy

    Directory of Open Access Journals (Sweden)

    Niku Oksala

    2014-06-01

    Full Text Available Background: Cerebral white matter lesions (WMLs predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. Methods: A total of 353 of 481 (73.4% consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%, amaurosis fugax (n = 52, 14.7%, transient ischemic attack (n = 135, 38.2% or ischemic stroke (n = 138, 39.1%, from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria in a blinded fashion. Internal carotid artery (ICA stenoses were angiographically graded (Results: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p Conclusions: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

  19. The Circle of Willis and White Matter Lesions in Patients with Carotid Atherosclerosis.

    Science.gov (United States)

    Li, Hua; Xiong, Yunyun; Xu, Gelin; Zhang, Renliang; Zhu, Wusheng; Yin, Qin; Ma, Minmin; Fan, Xiaobing; Yang, Fang; Liu, Wenhua; Duan, Zuowei; Liu, Xinfeng

    2015-08-01

    The correlation between cerebral atherosclerosis and white matter lesions (WMLs) in the elderly was controversial in the published articles, where the stenosis was often evaluated by ultrasonography, computed tomography angiography, or magnetic resonance angiography and collaterals were seldom considered. We hypothesized that collaterals influence WMLs. Our study was to explore the relationship between the circle of Willis and WMLs in a retrospective, hospital-based cohort of patients with carotid atherosclerosis. Two hundred eighty-six patients with carotid atherosclerosis were enrolled from the Nanjing Stroke Registry. They underwent magnetic resonance imaging evaluating WMLs and digital subtraction angiography evaluating both carotid atherosclerosis and collateral capacity of the circle of Willis. We tested the association between severe carotid atherosclerosis, the circle of Willis, and WMLs by logistic regression analysis. Severity of carotid atherosclerosis was not significantly associated with either periventricular or deep WMLs (P = .656 and .566, respectively). Number of carotid arteries with severe stenosis was not associated with the severity of either periventricular or deep WMLs (P = .721 and .263, respectively). Patency of the communicating arteries (CoA) was not associated with periventricular or deep WMLs (P = .561 and .703, respectively). Advanced age and hypertension were associated with periventricular WMLs (P = .001 and .008, respectively). Advanced age, hypertension, and prior stroke were associated with deep WMLs (P = .049, .048, and .001, respectively). The circle of Willis and severe carotid atherosclerosis may not be related to WMLs. Further larger studies are warranted to confirm or refute our findings. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Gypenoside attenuates white matter lesions induced by chronic cerebral hypoperfusion in rats.

    Science.gov (United States)

    Zhang, Guanglin; Zhao, Zhenwei; Gao, Li; Deng, Jianping; Wang, Benhan; Xu, Dunquan; Liu, Bolin; Qu, Youzhi; Yu, Jia; Li, Jian; Gao, Guodong

    2011-07-01

    Cerebral white matter lesions (WMLs) are frequently observed in vascular dementia and Alzheimer's disease and are believed to be responsible for cognitive dysfunction. The cerebral WMLs are most likely caused by chronic cerebral hypoperfusion and can be experimentally induced by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Previous studies found the involvement of oxidative stress and astrocytic activation in the cerebral WMLs of BCCAO rats. Gypenoside (GP), a pure component extracted from the Gyrostemma pentaphyllum Makino, a widely reputed medicinal plants in China, has been reported to have some neuroprotective effects via anti-oxidative stress and anti-inflammatory mechanisms. In the present study, we investigated the protective effect of GP against cerebral WMLs and the underlying mechanisms for its inhibition of cognitive decline in BCCAO rats. Adult male Sprague-Dawley rats were orally administered daily doses of 200 and 400mg/kg GP for 33 days after BCCAO, and spatial learning and memory were assessed using the Morris water maze. Following behavioral testing, oxygen free radical levels and antioxidative capability were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were also assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively. Activated astrocytes were also assessed by immunohistochemical staining and Western blotting with GFAP antibodies. The morphological changes were stained with Klüver-Barrera. Rats receiving 400mg/kg GP per day performed significantly better in tests for spatial learning and memory than saline-treated rats. GP 400mg/kg per day were found to markedly scavenge oxygen free radicals, enhance antioxidant abilities, decrease lipid peroxide production and oxidative DNA damage, and inhibit the astrocytic activation in corpus callosum and optic tract in BCCAO rats. However, GP 200mg/kg per day had no significant effects. GP may

  1. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

    Science.gov (United States)

    Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

    2014-01-01

    Cerebral palsy (CP) is a term to describe the spectrum of disorders of impaired motor and sensory function caused by a brain lesion occurring early during development. Diffusion MRI and tractography have been shown to be useful in the study of white matter (WM) microstructure in tracts likely to be impacted by the static brain lesion. The purpose of this study was to identify WM pathways with altered connectivity in children with unilateral CP caused by periventricular white matter lesions using a whole-brain connectivity approach. Data of 50 children with unilateral CP caused by periventricular white matter lesions (5-17 years; manual ability classification system [MACS] I = 25/II = 25) and 17 children with typical development (CTD; 7-16 years) were analysed. Structural and High Angular Resolution Diffusion weighted Images (HARDI; 64 directions, b = 3000 s/mm(2)) were acquired at 3 T. Connectomes were calculated using whole-brain probabilistic tractography in combination with structural parcellation of the cortex and subcortical structures. Connections with altered fractional anisotropy (FA) in children with unilateral CP compared to CTD were identified using network-based statistics (NBS). The relationship between FA and performance of the impaired hand in bimanual tasks (Assisting Hand Assessment-AHA) was assessed in connections that showed significant differences in FA compared to CTD. FA was reduced in children with unilateral CP compared to CTD. Seven pathways, including the corticospinal, thalamocortical, and fronto-parietal association pathways were identified simultaneously in children with left and right unilateral CP. There was a positive relationship between performance of the impaired hand in bimanual tasks and FA within the cortico-spinal and thalamo-cortical pathways (r(2) = 0.16-0.44; p < 0.05). This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these

  2. White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia.

    Science.gov (United States)

    Liu, Qing; Zhu, Zude; Teipel, Stefan J; Yang, Jianwei; Xing, Yi; Tang, Yi; Jia, Jianping

    2017-01-01

    Cholinergic deficiency has been implicated in the pathogenesis of vascular cognitive impairment (VCI), but the extent of involvement and underlying mechanism remain unclear. In this study, targeting the early stage of VCI, we determined regional atrophy within the basal forebrain and deficiency in cholinergic pathways in 25 patients with vascular cognitive impairment no dementia (VCIND) compared to 24 healthy elderly subjects. By applying stereotaxic cytoarchitectonic maps of the nucleus basalis of Meynert (NbM), no significant atrophy was identified in VCIND. Using probabilistic tractography analysis, our study tracked the two major white matter tracks which map to cholinergic pathways. We identified significantly lower fractional anisotropy (FA) in VCIND. Mediation analysis demonstrated that FA in the tracked pathways could fully account for the executive dysfunction, and partly mediate the memory and global cognition impairment. Our study suggests that the fibers mapped to the cholinergic pathways, but not the NbM, are significantly impaired in VCIND. MRI-based in vivo tracking of cholinergic pathways together with NbM measurement may become a valuable in vivo marker for evaluating the cholinergic system in cognitive disorders.

  3. Genome-wide association studies of cerebral white matter lesion burden

    NARCIS (Netherlands)

    M. Fornage (Myriam); S. Debette (Stéphanie); J.C. Bis (Joshua); R. Schmidt (Reinhold); M.A. Ikram (Arfan); C. Dufouil (Carole); S. Sigurdsson (Stefan); T. Lumley (Thomas); A.L. DeStefano (Anita); F. Fazekas (Franz); H.A. Vrooman (Henri); D.K. Shibata (Dean); P. Maillard (Pauline); A.P. Zijdenbos; A.V. Smith (Albert Vernon); H. Gudnason (Haukur); R. de Boer (Renske); M. Cushman (Mary Ann); B. Mazoyer (Bernard); G. Heiss (Gerardo); M.W. Vernooij (Meike); C. Enzinger (Christian); N.L. Glazer (Nicole); A. Beiser (Alexa); D.S. Knopman (David); M. Cavalieri (Margherita); W.J. Niessen (Wiro); T.B. Harris (Tamara); K. Petrovic (Katja); O.L. Lopez (Oscar); R. Au (Rhoda); J.C. Lambert (Jean Charles); A. Hofman (Albert); R.F. Gottesman (Rebecca); M. Garcia (Melissa); S.R. Heckbert (Susan); L.D. Atwood (Larry); D.J. Catellier (Diane); A.G. Uitterlinden (André); Q. Yang (Qiong Fang); T. Aspelund (Thor); J.R. Romero (Jose Rafael); K. Rice (Kenneth); K.D. Taylor (Kent); M.A. Nalls (Michael); J.I. Rotter (Jerome); R. Sharrett (Richey); P. Tikka-Kleemola (Päivi); P. Amouyel (Philippe); P.A. Wolf (Philip); A. van der Lugt (Aad); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); S. Seshadri (Sudha); C. Tzourio (Christophe); M.M.B. Breteler (Monique); T.H. Mosley (Thomas); W.T. Longstreth Jr; C. DeCarli (Charles); L.J. Launer (Lenore)

    2011-01-01

    textabstractObjective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased

  4. Hyperintense White Matter Lesions in 50 High-Altitude Pilots with Neurologic Decompression Sickness

    Science.gov (United States)

    2012-12-01

    with degradation of the myelin sheath , results in localized accumulation of extracellular water, which leads to an increased signal intensity on a T2...of cerebral health, commonly used to study the extent of the cerebral injury ( 9 ). Healthy cerebral white matter tracts are myelinated with

  5. Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

    NARCIS (Netherlands)

    Richard, E.; Gouw, A.A.; Scheltens, P.; van Gool, W.A.

    2010-01-01

    Background and Purpose:White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in

  6. Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

    NARCIS (Netherlands)

    Richard, Edo; Gouw, Alida A.; Scheltens, Philip; van Gool, Willem A.

    2010-01-01

    Background and Purpose-White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in

  7. Factors associated with increased white matter hyperintense lesion (WMHI) load in patients with systemic lupus erythematosus (SLE).

    Science.gov (United States)

    Shaharir, S S; Osman, S S; Md Rani, S A; Sakthiswary, R; Said, M S M

    2018-01-01

    Introduction White matter hyperintense (WMHI) lesions are the most common finding in magnetic resonance imaging (MRI) of the brain in patients with systemic lupus erythematosus (SLE). Objective The objective of this article is to determine the clinical factors associated with an increase in WMHI lesion load among SLE patients. Method A total of 83 SLE patients with MRI of the brain from National University of Malaysia Medical Centre were included. The WMHI lesion load was determined using the Scheltens score and Fazekas scale, and their distribution was divided into the deep white matter (DWMHI) and periventricular (PVH) regions. The clinical correlates of WMHI lesions were initially determined using univariate analyses and subsequently multivariable regression analyses were performed to determine the independent factors of increased WMHI lesion load. Results MRI of the brain of 46 patients who had WMHI lesions were compared with 37 patients with normal MRI. We found significant association between the presence of WMHI lesions and age, presence of cerebral infarcts, positive antiphospholipid antibody (aPL), active disease, neuropsychiatric lupus (NPSLE) and disease damage. Age, SLEDAI scores, cerebral infarcts and disease damage were significantly associated with higher DWMHI and PVH Scheltens scores. Meanwhile, patients with active lupus nephritis (LN), lower serum albumin and more severe proteinuria were associated with larger Fazekas WMHI lesions. Multivariable regression analysis revealed that the independent factors associated with presence of WMHI lesions were positive aPL and SLEDAI scores ( p SLE disease. Conclusion Presence of WMHI lesions in SLE was significantly associated with cerebral infarcts, aPL and high general SLE activity, suggesting both inflammation and ischaemia as the underlying pathology of these lesions.

  8. Strategic Role of Frontal White Matter Tracts in Vascular Cognitive Impairment: A Voxel-Based Lesion-Symptom Mapping Study in CADASIL

    Science.gov (United States)

    Duering, Marco; Zieren, Nikola; Herve, Dominique; Jouvent, Eric; Reyes, Sonia; Peters, Nils; Pachai, Chahin; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2011-01-01

    Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and…

  9. An automated method for segmenting white matter lesions through multi-level morphometric feature classification with application to lupus

    Directory of Open Access Journals (Sweden)

    Mark Scully

    2010-04-01

    Full Text Available We demonstrate an automated, multi-level method to segment white matter brain lesions and apply it to lupus. The method makes use of local morphometric features based on multiple MR sequences, including T1-weighted, T2-weighted, and Fluid Attenuated Inversion Recovery. After preprocessing, including co-registration, brain extraction, bias correction, and intensity standardization, 49 features are calculated for each brain voxel based on local morphometry. At each level of segmentation a supervised classifier takes advantage of a different subset of the features to conservatively segment lesion voxels, passing on more difficult voxels to the next classifier. This multi-level approach allows for a fast lesion classification method with tunable trade-offs between sensitivity and specificity producing accuracy comparable to a human rater.

  10. Increased frequency of white matter lesions in patients with osteonecrosis (WMLeOn) of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Hadjigeorgiou, Georgios M. E-mail: gmhadji@med.uth.gr; Karantanas, Apostolos H.; Zibis, Aristidis; Dardiotis, Efthimios; Aggelakis, Konstantinos; Papadimitriou, Alexandros; Malizos, Konstantinos

    2004-06-01

    White matter lesions (WML) are commonly seen in cerebral MR imaging in normal and demented elderly people or young people suffering from migraine. We present data showing that WML are detected in an unexpectedly high frequency (56.9%) in patients with non-traumatic osteonecrosis of the femoral head compared to age and sex-matched controls. We designated the coexistence of WML and osteonecrosis as white matter lesions in osteonecrosis (WMLeON). We examined the possible association of WMLeON with hyperlipidaemia and other risk factors for WML or osteonecrosis of the femoral head. The frequency of history of corticosteroid treatment was statistically lower in patients with WMLeON (58.6%) compared to those without it (90.1%) (P=0.03). We found no association of WMLeON with diabetes, stroke, hyperlipidaemia, migraine, smoking, alcohol consumption, hypertension, atrial fibrillation, or systemic lupus erythematosus. Although, the clinical significance of WMLeON is still unknown, this finding supports, at least, the hypothesis that non-traumatic osteonecrosis is indeed a multisystem disorder rather than a disease of human skeleton.

  11. Patient-specific 3D FLAIR for enhanced visualization of brain white matter lesions in multiple sclerosis.

    Science.gov (United States)

    Gabr, Refaat E; Pednekar, Amol S; Govindarajan, Koushik A; Sun, Xiaojun; Riascos, Roy F; Ramírez, María G; Hasan, Khader M; Lincoln, John A; Nelson, Flavia; Wolinsky, Jerry S; Narayana, Ponnada A

    2017-08-01

    To improve the conspicuity of white matter lesions (WMLs) in multiple sclerosis (MS) using patient-specific optimization of single-slab 3D fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Sixteen MS patients were enrolled in a prospective 3.0T MRI study. FLAIR inversion time and echo time were automatically optimized for each patient during the same scan session based on measurements of the relative proton density and relaxation times of the brain tissues. The optimization criterion was to maximize the contrast between gray matter (GM) and white matter (WM), while suppressing cerebrospinal fluid. This criterion also helps increase the contrast between WMLs and WM. The performance of the patient-specific 3D FLAIR protocol relative to the fixed-parameter protocol was assessed both qualitatively and quantitatively. Patient-specific optimization achieved a statistically significant 41% increase in the GM-WM contrast ratio (P < 0.05) and 32% increase in the WML-WM contrast ratio (P < 0.01) compared with fixed-parameter FLAIR. The increase in WML-WM contrast ratio correlated strongly with echo time (P < 10-11 ). Two experienced neuroradiologists indicated substantially higher lesion conspicuity on the patient-specific FLAIR images over conventional FLAIR in 3-4 cases (intrarater correlation coefficient ICC = 0.72). In no case was the image quality of patient-specific FLAIR considered inferior to conventional FLAIR by any of the raters (ICC = 0.32). Changes in proton density and relaxation times render fixed-parameter FLAIR suboptimal in terms of lesion contrast. Patient-specific optimization of 3D FLAIR increases lesion conspicuity without scan time penalty, and has potential to enhance the detection of subtle and small lesions in MS. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:557-564. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Presence of a central vein within white matter lesions on susceptibility weighted imaging: a specific finding for multiple sclerosis?

    Energy Technology Data Exchange (ETDEWEB)

    Lummel, Nina; Boeckh-Behrens, Tobias; Brueckmann, Hartmut; Linn, Jennifer [University of Munich, Department of Neuroradiology, Munich (Germany); Schoepf, Veronika [University of Munich, Department of Neuroradiology, Munich (Germany); Medical University of Vienna, MR Centre of Excellence, Vienna (Austria); Burke, Michael [GE Healthcare, Solingen (Germany)

    2011-05-15

    Susceptibility weighted imaging depicts the perivenous extent of multiple sclerosis white matter lesions (MS-WML) in vivo by directly visualizing their centrally running vein. The aim of this study was to investigate the specificity of this finding for MS. Fifteen patients with MS and 15 patients with microangiopathic white matter lesions (mWML) underwent 3T MRI, including a fluid-attenuated inversion recovery sequence (FLAIR) and a susceptibility weighted angiography (SWAN). All WMLs were identified on FLAIR and assigned to one of the following localizations: supratentorial peripheral, supratentorial periventricular, or infratentorial. Subsequently, the presence of a central vein within these lesions was assessed on SWAN. A total of 711 MS-WMLs and 1,119 m-WMLs were identified on FLAIR, all of which could also be visualized on SWAN. A central vein was detectable in 80% of the MS-WMLs and in 78% of the m-WMLs (in 73% and 76% of the peripheral, in 92% and 94% of the periventricular, and in 71% and 75% of the infratentorial MS-WMLs and m-WMLs, respectively). With regard to the supratentorial peripheral lesions, significantly more m-WMLs showed a central vein compared to the MS-WMLs. For the other localizations, there was no significant difference between the groups with regard to the percentage of lesions with central vein. Our results indicate that the detection of a central vein within a WML should not be considered a specific finding for MS; it is also found in WMLs of other etiologies. (orig.)

  13. Temporal lesions and widespread involvement of white matter associated with multi-organ inflammatory disease in human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

    Science.gov (United States)

    Mendes, Gustavo B; Kalil, Rosangela S; Rosadas, Carolina; de Freitas, Marcos R G; Puccioni-Sohler, Marzia

    2014-08-01

    Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord, characterized by spastic paraparesis, back pain, and sphincter disorders. Involvement of multiple organs and encephalopathy are uncommon in HAM/TSP. Nonspecific small white matter lesions of unknown etiology, mainly in the periventricular and subcortical regions, have been found on brain magnetic resonance imaging of HAM/TSP patients. Bitemporal lesions have rarely been described. We report the case of a 54-year-old woman diagnosed with HAM/TSP who presented subclinical cognitive deficits associated with bitemporal and widespread white matter lesions. The cerebrospinal fluid (CSF) was inflammatory (blood-CSF barrier dysfunction, intrathecal synthesis of total and HTLV-1 IgG). The proviral load was higher in cerebrospinal fluid than in peripheral blood mononuclear cells. The neurological picture was complicated by multi-organ inflammatory disease (Hashimoto's thyroiditis, uveitis, anemia, and chronic renal failure). This case highlights the potential multisystem inflammatory nature of HTLV-1 infection, with a wide spectrum of manifestations. In cases of HAM/TSP with multi-organ inflammatory disease, encephalic involvement should be investigated, even in the absence of clinical manifestations. Also bitemporal lesions can be the consequence of intense and diffuse inflammation associated with HTLV-1 infection. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Hypertensive encephalopathy mimicking cerebral vasculitis with pontine oedema, cerebellar white matter lesions and multiple cerebral infarctions.

    Science.gov (United States)

    Ceccarelli, Daniela; Hargroves, David; Balogun, Ibrahim; Webb, Thomas

    2017-07-19

    A 47-year-old man with poorly controlled hypertension presented with headaches, right-sided weakness and dysarthria. CT and MRI scans of the brain showed widespread abnormalities including significant pontine oedema, basal ganglia and corona radiata infarctions and cerebellar white matter high signal. Imaging of the intracerebral vasculature also demonstrated wall irregularities. Initially a central nervous system inflammatory disorder was thought to be the most likely diagnosis, possibly acute demyelinating encephalomyelitis or cerebral vasculitis, and the patient was treated with high-dose intravenous steroids. The diagnosis of hypertensive encephalopathy was made because (1) the patient was hypertensive and (2) the patients MRI findings resolved with antihypertensive treatment.Blood pressure treatment was instigated from admission, and the patients symptoms improved with resolution of the radiological abnormalities. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. White matter lesions as a feature of cognitive impairment, low vitality and other symptoms of geriatric syndrome in the elderly.

    Science.gov (United States)

    Sonohara, Kazuki; Kozaki, Koichi; Akishita, Masahiro; Nagai, Kumiko; Hasegawa, Hiroshi; Kuzuya, Masafumi; Yokote, Koutaro; Toba, Kenji

    2008-06-01

    White matter lesions (WML) are common findings on magnetic resonance imaging (MRI) in elderly persons. In this study, we analyzed the relation of WML with global cognitive function, depression, vitality/volition, and 19 symptoms of geriatric syndrome in Japanese elderly patients who attended three university geriatric outpatient clinics. Two hundred and eighty-six subjects (103 men and 183 women; mean +/- standard deviation age, 74.5 +/- 7.8 years) were included in this study. MRI scans were performed for the diagnosis of WML, and the severity of periventricular and deep white matter hyperintensities (PVH and DWMH) was rated semiquantitatively. Concurrently, all subjects underwent tests of cognitive function, depressive state and vitality, and were examined for 19 symptoms of geriatric syndrome. The study subjects showed cognitive decline, depression and low vitality, all to a mild extent. Univariate linear regression analysis showed a negative correlation between the severity of WML and cognitive function or vitality. Multiple logistic analysis revealed that the severity of WML was a significant determinant of cognitive impairment and low vitality, after adjustment for confounding factors such as age, sex and concomitant diseases. PVH and/or DWMH score was significantly greater in subjects who exhibited 13 out of 19 symptoms of geriatric syndrome. Logistic regression analysis indicated that WML were associated with psychological disorders, gait disturbance, urinary problems and parkinsonism. WML were associated with various symptoms of functional decline in older persons. Evaluating WML in relation to functional decline would be important for preventing disability in elderly people.

  16. Automated Bayesian Segmentation of Microvascular White-Matter Lesions in the ACCORD-MIND Study

    National Research Council Canada - National Science Library

    Herskovits, E H; Bryan, R N; Yang, F

    2008-01-01

    Purpose: Automatic brain-lesion segmentation has the potential to greatly expand the analysis of the relationships between brain function and lesion locations in large-scale epidemiologic studies, such as the ACCORD-MIND study...

  17. Review of automatic segmentation methods of multiple sclerosis white matter lesions on conventional magnetic resonance imaging.

    Science.gov (United States)

    García-Lorenzo, Daniel; Francis, Simon; Narayanan, Sridar; Arnold, Douglas L; Collins, D Louis

    2013-01-01

    Magnetic resonance (MR) imaging is often used to characterize and quantify multiple sclerosis (MS) lesions in the brain and spinal cord. The number and volume of lesions have been used to evaluate MS disease burden, to track the progression of the disease and to evaluate the effect of new pharmaceuticals in clinical trials. Accurate identification of MS lesions in MR images is extremely difficult due to variability in lesion location, size and shape in addition to anatomical variability between subjects. Since manual segmentation requires expert knowledge, is time consuming and is subject to intra- and inter-expert variability, many methods have been proposed to automatically segment lesions. The objective of this study was to carry out a systematic review of the literature to evaluate the state of the art in automated multiple sclerosis lesion segmentation. From 1240 hits found initially with PubMed and Google scholar, our selection criteria identified 80 papers that described an automatic lesion segmentation procedure applied to MS. Only 47 of these included quantitative validation with at least one realistic image. In this paper, we describe the complexity of lesion segmentation, classify the automatic MS lesion segmentation methods found, and review the validation methods applied in each of the papers reviewed. Although many segmentation solutions have been proposed, including some with promising results using MRI data obtained on small groups of patients, no single method is widely employed due to performance issues related to the high variability of MS lesion appearance and differences in image acquisition. The challenge remains to provide segmentation techniques that work in all cases regardless of the type of MS, duration of the disease, or MRI protocol, and this within a comprehensive, standardized validation framework. MS lesion segmentation remains an open problem. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. MR Spectroscopy evaluation of white matter signal abnormalities of different non-neoplastic brain lesions

    Directory of Open Access Journals (Sweden)

    Randa O. Kaddah

    2016-03-01

    Conclusion: MRS is a noninvasive additional MRI technique to define the nature of non-neoplastic brain lesions. Together with image analysis, it may be the key to etiologic diagnosis or, at least, definition of the group where the lesion is classified, by detecting changes in different metabolites and peaks of inflammation.

  19. FLAIR* to visualize veins in white matter lesions: A new tool for the diagnosis of multiple sclerosis?

    Energy Technology Data Exchange (ETDEWEB)

    Campion, T.; Turner, B.P.; Schmierer, K. [Queen Mary University of London, Blizard Institute (Neuroscience), London (United Kingdom); Barts Health NHS Trust, Emergency Care and Acute Medicine Clinical Academic Group Neuroscience, The Royal London Hospital, London (United Kingdom); Smith, R.J.P. [Queen Mary University of London, Blizard Institute (Neuroscience), London (United Kingdom); Gloucestershire Hospitals NHS Trust, Cheltenham (United Kingdom); Altmann, D.R. [London School of Hygiene and Tropical Medicine, Department of Medical Statistics, London (United Kingdom); Brito, G.C. [Queen Mary University of London, Blizard Institute (Neuroscience), London (United Kingdom); Evanson, J. [Barts Health NHS Trust, Emergency Care and Acute Medicine Clinical Academic Group Neuroscience, The Royal London Hospital, London (United Kingdom); George, I.C. [NIH, Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD (United States); Yale School of Medicine, Department of Neurology, New Haven, CT (United States); Sati, P.; Reich, D.S. [NIH, Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD (United States); Miquel, M.E. [Barts Health NHS Trust, Emergency Care and Acute Medicine Clinical Academic Group Neuroscience, The Royal London Hospital, London (United Kingdom); Queen Mary University of London, William Harvey Research Institute (Cardiovascular Biomedical Research Unit), London (United Kingdom)

    2017-10-15

    To explore the potential of a post-processing technique combining FLAIR and T{sub 2}* (FLAIR*) to distinguish between lesions caused by multiple sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting. FLAIR and T{sub 2}* head datasets acquired at 3T of 25 people with relapsing MS (pwRMS) and ten with pwSVD were used. After post-processing, FLAIR* maps were used to determine the proportion of white matter lesions (WML) showing the 'vein in lesion' sign (VIL), a characteristic histopathological feature of MS plaques. Sensitivity and specificity of MS diagnosis were examined on the basis of >45% VIL{sup +} and >60% VIL{sup +} WML, and compared with current dissemination in space (DIS) MRI criteria. All pwRMS had >45% VIL{sup +} WML (range 58-100%) whilst in pwSVD the proportion of VIL{sup +} WML was significantly lower (0-64%; mean 32±20%). Sensitivity based on >45% VIL{sup +} was 100% and specificity 80% whilst with >60% VIL{sup +} as the criterion, sensitivity was 96% and specificity 90%. DIS criteria had 96% sensitivity and 40% specificity. FLAIR* enables VIL{sup +} WML detection in a clinical setting, facilitating differentiation of MS from SVD based on brain MRI. (orig.)

  20. Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE).

    Science.gov (United States)

    Launer, L J; Berger, K; Breteler, M M B; Dufouil, C; Fuhrer, R; Giampaoli, S; Nilsson, L-G; Pajak, A; de Ridder, M; van Dijk, E J; Sans, S; Schmidt, R; Hofman, A

    2006-01-01

    White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions.

  1. Speech and language disorders secondary to diffuse subcortical vascular lesions: Neurolinguistic and acoustic analysis. A case report.

    Science.gov (United States)

    Tomić, Gordana; Stojanović, Milena; Pavlović, Aleksandra; Stanković, Predrag; Zidverc-Trajković, Jasna; Pavlović, Dragan; Marković-Jovanović, Zagorka; Covicković-Sternić, Nadezda

    2009-08-15

    Subcortical white matter (WM) plays an important role in speech production and language processing. Most frequently, cerebral WM lesions are secondary to small vessel disease in patients with vascular risk factors. We report the case of a 53-year-old man with history of hypertension and ischemic subcortical lesions, who presented with speech difficulties and mild cognitive impairment. Language and cognitive assessment included Boston Diagnostic Aphasia Examination, Boston Naming Test, Rey Auditory-Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Scale for Evaluation of Perceptive Characteristics of Voice and Speech, and Multidimensional Evaluation of Speech and Voice. Brain MRI showed ischemic WM lesions and lacunar infarcts in the brainstem and right cerebellum. Cognitive testing revealed mild cognitive impairment, predominantly affecting attention and executive functions. Speech and language analysis demonstrated dysarthria, dysphonia with hypophonia, and imprecise articulation, as well as short rushes of speech, palilalia and mild subcortical dysphasia. Neurolinguistic and acoustic analysis in patients with ischemic WM lesions can provide additional information in the understanding of language and speech disturbances, and can assist in patient management.

  2. Automatic white matter lesion segmentation using an adaptive outlier detection method

    National Research Council Canada - National Science Library

    Ong, Kok Haur; Ramachandram, Dhanesh; Mandava, Rajeswari; Shuaib, Ibrahim Lutfi

    2012-01-01

    ...) regions in cranial magnetic resonance imaging (MRI). WM lesions are often observed in older populations and are important indicators of stroke, multiple sclerosis, dementia and other brain-related disorders...

  3. Automatic segmentation of white matter lesions on magnetic resonance images of the brain by using an outlier detection strategy.

    Science.gov (United States)

    Wang, Rui; Li, Chao; Wang, Jie; Wei, Xiaoer; Li, Yuehua; Hui, Chun; Zhu, Yuemin; Zhang, Su

    2014-12-01

    White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the-art WML segmentation methods. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. The reduction of regional cerebral blood flow in normal-appearing white matter is associated with the severity of white matter lesions in elderly: a Xeon-CT study.

    Directory of Open Access Journals (Sweden)

    Jianhui Fu

    Full Text Available White matter lesions (WMLs in normal elderly are related to chronic ischemia, and progression of WML occurs mostly in moderate to severe disease. However, the mechanism is uncertain. Thus, we enrolled fifty-six normal elderly patients without large artery disease. The severity of WML on MRI was graded as grade 0, I, II and III using the modified Fazekas scale. Cerebral blood flow (CBF was measured by Xenon-CT. We found that CBF (mL/100 g/min within periventricular lesions and in the right and left centrum semiovales were 20.33, 21.27 and 21.03, respectively, in group I; 16.33, 15.55 and 15.91, respectively, in group II; and 14.05, 14.46 and 14.23, respectively, in group III. CBF of normal-appearing white matter (NAWM around periventricular areas and in the right and left centrum semiovales were 20.79, 22.26 and 22.15, respectively, in group 0; 21.12, 22.17 and 22.25, respectively, in group I; 18.02, 19.45 and 19.62, respectively, in group II; and 16.38, 18.18 and 16.74, respectively, in group III. Significant reductions in CBF were observed not only within lesions but also in NAWM surrounding the lesions. In addition, CBF was reduced significantly within lesions compared to NAWM of the same grade. Furthermore, CBF was reduced significantly in NAWM in grades II and III when compared to grades 0 and I. Our finding indicates that ischemia may play a role in the pathogenesis of WML. Additionally, our finding provides an alternative explanation for finding that the progression of WML occurred more commonly in patients with moderate to severe WML.

  5. Temporal lesions and widespread involvement of white matter associated with multi-organ inflammatory disease in human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)

    National Research Council Canada - National Science Library

    Mendes, Gustavo B; Kalil, Rosangela S; Rosadas, Carolina; de Freitas, Marcos R G; Puccioni-Sohler, Marzia

    2014-01-01

    .... Bitemporal lesions have rarely been described. We report the case of a 54-year-old woman diagnosed with HAM/TSP who presented subclinical cognitive deficits associated with bitemporal and widespread white matter lesions...

  6. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    Science.gov (United States)

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all Pactivity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. L-carnitine enhances axonal plasticity and improves white-matter lesions after chronic hypoperfusion in rat brain.

    Science.gov (United States)

    Ueno, Yuji; Koike, Masato; Shimada, Yoshiaki; Shimura, Hideki; Hira, Kenichiro; Tanaka, Ryota; Uchiyama, Yasuo; Hattori, Nobutaka; Urabe, Takao

    2015-03-01

    Chronic cerebral hypoperfusion causes white-matter lesions (WMLs) with oxidative stress and cognitive impairment. However, the biologic mechanisms that regulate axonal plasticity under chronic cerebral hypoperfusion have not been fully investigated. Here, we investigated whether L-carnitine, an antioxidant agent, enhances axonal plasticity and oligodendrocyte expression, and explored the signaling pathways that mediate axonal plasticity in a rat chronic hypoperfusion model. Adult male Wistar rats subjected to ligation of the bilateral common carotid arteries (LBCCA) were treated with or without L-carnitine. L-carnitine-treated rats exhibited significantly reduced escape latency in the Morris water maze task at 28 days after chronic hypoperfusion. Western blot analysis indicated that L-carnitine increased levels of phosphorylated high-molecular weight neurofilament (pNFH), concurrent with a reduction in phosphorylated phosphatase tensin homolog deleted on chromosome 10 (PTEN), and increased phosphorylated Akt and mammalian target of rapamycin (mTOR) at 28 days after chronic hypoperfusion. L-carnitine reduced lipid peroxidation and oxidative DNA damage, and enhanced oligodendrocyte marker expression and myelin sheath thickness after chronic hypoperfusion. L-carnitine regulates the PTEN/Akt/mTOR signaling pathway, and enhances axonal plasticity while concurrently ameliorating oxidative stress and increasing oligodendrocyte myelination of axons, thereby improving WMLs and cognitive impairment in a rat chronic hypoperfusion model.

  8. Association of white-matter lesions with brain atrophy markers: the three-city Dijon MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Godin, O.; Alperovitch, A.; Tzourio, Ch.; Dufouil, C. [Inserm U708 ' Neuroepidemiology' , Paris (France); Godin, O.; Alperovitch, A.; Tzourio, Ch.; Dufouil, C. [UPMC University Paris 6 (France); Mazoyer, B. [Institut Universitaire de France, Paris (France); Maillard, P.; Crivello, F.; Mazoyer, B. [CNRS, CI-NAPS UMR6232 (France); Maillard, P.; Crivello, F.; Mazoyer, B. [CEA, DSV/I2BM/CI-NAPS (France); Maillard, P.; Crivello, F.; Mazoyer, B. [Universite de Caen Basse-Normande (France); Mazoyer, B. [Centre Hospitalier et Universitaire de Caen, Caen (France)

    2009-07-01

    Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1, 792 elderly subjects aged 65-80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM ({beta} = -0.03, p {<=} 0.0001) and hippocampal volumes ({beta} = -0.75, p = 0.0009) and positively with CSF volumes (beta 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of non demented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors. (authors)

  9. Tau Pathology and Parietal White Matter Lesions Have Independent but Synergistic Effects on Early Development of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Joakim Hertze

    2013-04-01

    Full Text Available Background: White matter lesions (WMLs are a common finding in patients with dementia. This study investigates the relationship between WMLs, hyperphosphorylated tau (P-tau in cerebrospinal fluid (CSF and apolipoprotein E (APOE ε4 genotype in prodromal Alzheimer's disease (AD. Methods: Baseline levels of tau, P-tau and β-amyloid 1-42 in CSF, the presence of WMLs in the brain, and the APOE genotype were ascertained in 159 patients with mild cognitive impairment (MCI and 38 cognitively healthy controls. Results: After 5.7 years, 58 patients had developed AD. In this group, patients with normal levels of CSF P-tau had higher levels of WMLs in the parietal regions than those with pathological P-tau levels (p Conclusions: We suggest that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain. In patients with a more low-grade AD pathology, WMLs in the parietal lobes might increase the risk of developing dementia.

  10. New multispectral MRI data fusion technique for white matter lesion segmentation: method and comparison with thresholding in FLAIR images.

    Science.gov (United States)

    Hernández, Maria del C Valdés; Ferguson, Karen J; Chappell, Francesca M; Wardlaw, Joanna M

    2010-07-01

    Brain tissue segmentation by conventional threshold-based techniques may have limited accuracy and repeatability in older subjects. We present a new multispectral magnetic resonance (MR) image analysis approach for segmenting normal and abnormal brain tissue, including white matter lesions (WMLs). We modulated two 1.5T MR sequences in the red/green colour space and calculated the tissue volumes using minimum variance quantisation. We tested it on 14 subjects, mean age 73.3 +/- 10 years, representing the full range of WMLs and atrophy. We compared the results of WML segmentation with those using FLAIR-derived thresholds, examined the effect of sampling location, WML amount and field inhomogeneities, and tested observer reliability and accuracy. FLAIR-derived thresholds were significantly affected by the location used to derive the threshold (P = 0.0004) and by WML volume (P = 0.0003), and had higher intra-rater variability than the multispectral technique (mean difference +/- SD: 759 +/- 733 versus 69 +/- 326 voxels respectively). The multispectral technique misclassified 16 times fewer WMLs. Initial testing suggests that the multispectral technique is highly reproducible and accurate with the potential to be applied to routinely collected clinical MRI data.

  11. New multispectral MRI data fusion technique for white matter lesion segmentation: method and comparison with thresholding in FLAIR images

    Energy Technology Data Exchange (ETDEWEB)

    Del C. Valdes Hernandez, Maria [University of Edinburgh, SFC Brain Imaging Research Centre, Division of Clinical Neurosciences, School of Molecular and Clinical Medicine, Edinburgh (United Kingdom); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh (United Kingdom); University of Edinburgh, SFC Brain Imaging Research Centre, Image Analysis Lab, Division of Clinical Neurosciences, Western General Hospital, Edinburgh (United Kingdom); Ferguson, Karen J.; Chappell, Francesca M. [University of Edinburgh, SFC Brain Imaging Research Centre, Division of Clinical Neurosciences, School of Molecular and Clinical Medicine, Edinburgh (United Kingdom); Wardlaw, Joanna M. [University of Edinburgh, SFC Brain Imaging Research Centre, Division of Clinical Neurosciences, School of Molecular and Clinical Medicine, Edinburgh (United Kingdom); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh (United Kingdom)

    2010-07-15

    Brain tissue segmentation by conventional threshold-based techniques may have limited accuracy and repeatability in older subjects. We present a new multispectral magnetic resonance (MR) image analysis approach for segmenting normal and abnormal brain tissue, including white matter lesions (WMLs). We modulated two 1.5T MR sequences in the red/green colour space and calculated the tissue volumes using minimum variance quantisation. We tested it on 14 subjects, mean age 73.3 {+-} 10 years, representing the full range of WMLs and atrophy. We compared the results of WML segmentation with those using FLAIR-derived thresholds, examined the effect of sampling location, WML amount and field inhomogeneities, and tested observer reliability and accuracy. FLAIR-derived thresholds were significantly affected by the location used to derive the threshold (P = 0.0004) and by WML volume (P = 0.0003), and had higher intra-rater variability than the multispectral technique (mean difference {+-} SD: 759 {+-} 733 versus 69 {+-} 326 voxels respectively). The multispectral technique misclassified 16 times fewer WMLs. Initial testing suggests that the multispectral technique is highly reproducible and accurate with the potential to be applied to routinely collected clinical MRI data. (orig.)

  12. Elevated leukocyte count in asymptomatic subjects is associated with a higher risk for cerebral white matter lesions.

    Science.gov (United States)

    Kim, Chi Kyung; Lee, Seung-Hoon; Kim, Beom Joon; Ryu, Wi-Sun; Choi, Seung Ho; Oh, Byung-Hee; Yoon, Byung-Woo

    2011-04-01

    Cerebral white matter lesions (WMLs) are radiologic markers of small vessel disease in brain, and inflammatory processes were related to WMLs. We propose to determine if elevated leukocyte count was associated with a higher risk of WMLs. 1586 asymptomatic subjects who visited our hospital for a routine health check-up were enrolled. Leukocyte counts were measured and the presence of moderate to severe WMLs was determined by brain MRI. Thirty (1.9%) had moderate to severe WMLs, and a significant greater proportion (4.1%) of subjects in the highest leukocyte count quartile had moderate to severe WMLs. After adjusting by C-reactive protein, aspirin use and cardiovascular risk factors, the highest quartile of leukocyte count (≥6.7×10⁹/L) was significantly associated with moderate to severe WMLs compared with the lowest quartile [adjusted odds ratio, 4.03; 95% confidence interval, 1.05-15.5]. The authors report for the first time that an elevated leukocyte count is independently associated with moderate to severe WMLs. Copyright © 2010. Published by Elsevier B.V.

  13. A prospective pilot investigation of brain volume, white matter hyperintensities and haemorrhagic lesions after mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Michael eJarrett

    2016-02-01

    Full Text Available Traumatic brain injury (TBI is among the most common neurological disorders. Haemorrhagic lesions and white matter hyperintensities (WMH are radiological features associated with moderate and severe traumatic brain injury TBI. Brain volume reductions have also been observed during the months following injury. In concussion, no signs of injury are observed on conventional MRI, which may be a true feature of concussion or merely due to the limited sensitivity of imaging techniques used so far. Moreover, it is not known whether volume reductions are due to the resolution of trauma related edema or a true volume loss. Forty five collegiate level ice hockey players (20 female and 15 controls (9 female 40 players underwent 3T MRI for haemorrhages (multi echo susceptibility weighted imaging (SWI, WMH (three dimensional FLAIR and brain volume at the beginning and the end of the hockey season. Concussed athletes underwent additional imaging and neuropsychological testing atthree days, two weeks, and two months after injury. At the end of the hockey season, brain volume was reduced compared to controls by 0.32% (p<0.034 in the whole cohort and by 0.26% (p<0.09 in the concussed athletes. Two weeks and two months after concussion, brain volume was reduced by -0.08% (p=0.027 and -0.23% (p=0.035, respectively. In athletes, the WMH were significantly closer to the interface between grey matter and white matter compared to controls. No significant changes in thenumber of WMH over the duration of the study were found in athletes. No microhaemorrhages were detected as a result of concussion or playing a season of ice hockey. We conclude that mild TBI does not lead to transient increases in brain volume and no new microbleeds or WMH are detectable after concussion. Brain volume reductions appear by two weeks after concussion and persist until at least two months after concussion. Brain volume is reduced between the beginning and the end of the icehockey season.

  14. Differences between suicide attempters and nonattempters in depressed older patients: depression severity, white-matter lesions, and cognitive functioning.

    Science.gov (United States)

    Sachs-Ericsson, Natalie; Hames, Jennifer L; Joiner, Thomas E; Corsentino, Elizabeth; Rushing, Nicole C; Palmer, Emily; Gotlib, Ian H; Selby, Edward A; Zarit, Steven; Steffens, David C

    2014-01-01

    The population of older adults with major depressive disorder (MDD) has the highest rate of suicide. White-matter brain lesions (WML) are a potential biologic marker for suicidality in young and middle-aged adults and are correlated with cognitive impairment in older adults. In this study of older patients with MDD, we examined 1) if a history of suicide attempts was associated with a more severe course of MDD; 2) if WML are a biologic marker for suicide; and 3) if suicide attempt history is associated with cognitive impairment mediated by WML. Data from the Neurocognitive Outcomes of Depression in the Elderly study. Depressed patients (60+) who had ever attempted suicide (n = 23) were compared with depressed patients (60+) who had not attempted suicide (n = 223). Baseline and follow-up assessments were obtained for depressive symptoms (every 3 months) and cognitive functioning (every 6 months) over 2 years. Three magnetic resonance imaging scans were conducted. At baseline, suicide attempters reported more severe past and present symptoms (e.g., depressive symptoms, current suicidal thoughts, psychotic symptoms, earlier age of onset, and more lifetime episodes) than nonattempters. Suicide attempters had more left WML at baseline, and suicide attempt history predicted a greater growth in both left and right WML. WML predicted cognitive decline; nonetheless, a history of suicide attempt was unrelated to cognitive functioning. Severity of depressive symptoms and WML are associated with suicide attempts in geriatric depressed patients. Suicide attempts predicted neurologic changes, which may contribute to poorer long-term outcomes in elder attempters. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.

    Science.gov (United States)

    Mortamais, Marion; Portet, Florence; Brickman, Adam M; Provenzano, Frank A; Muraskin, Jordan; Akbaraly, Tasnime N; Berr, Claudine; Touchon, Jacques; Bonafé, Alain; le Bars, Emmanuelle; Menjot de Champfleur, Nicolas; Maller, Jerome J; Meslin, Chantal; Sabatier, Robert; Ritchie, Karen; Artero, Sylvaine

    2014-11-01

    Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions.

    Science.gov (United States)

    Scheck, Simon M; Pannek, Kerstin; Raffelt, David A; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

    2015-01-01

    In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC-precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC-superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = -0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function.

  17. Cognitive deficits are associated with frontal and temporal lobe white matter lesions in middle-aged adults living in the community.

    Directory of Open Access Journals (Sweden)

    David Bunce

    Full Text Available BACKGROUND: The association between brain white matter lesions and cognitive impairment in old age is well established. However, little is known about this association in midlife. As this information will inform policy for early preventative healthcare initiatives, we investigated non-periventricular frontal, temporal, parietal and occipital lobe white matter hyperintensities (WMH in relation to cognitive function in 428 (232 women community-dwelling adults aged 44 to 48 years. RESULTS: Frontal white matter lesions were significantly associated with greater intraindividual RT variability in women, while temporal WMH were associated with face recognition deficits in men. Parietal and occipital lobe lesions were unrelated to cognitive performance. These findings did not differ when education and a range of health variables, including vascular risk factors, were taken into account. CONCLUSION: Gender differences in WMH-cognition associations are discussed, and we conclude that small vessel disease is present in midlife and has functional consequences which are generally not recognized. Preventative strategies should, therefore, begin early in life.

  18. Rat white matter injury model induced by endothelin-1 injection: technical modification and pathological evaluation.

    Science.gov (United States)

    Ono, Hideaki; Imai, Hideaki; Miyawaki, Satoru; Nakatomi, Hirofumi; Saito, Nobuhito

    2016-01-01

    White matter injury is an important cause of functional disability of the brain. We comprehensively analyzed a modified endothelin-1 (ET‑1) injection-induced white matter injury model in the rat which is very valuable for investigating the underlying mechanisms of subcortical ischemic stroke. ET-1 was stereotactically injected into the internal capsule of the rat. To avoid complications with leakage of ET-1 into the lateral ventricle, the safest trajectory angle to the target was established. Rats with white matter injury were extensively evaluated for structural changes and functional sequelae, using motor function tests, magnetic resonance (MR) imaging, histopathology evolution, volume estimation of the lesion, and neuroanatomical identification of affected neurons using the retrograde tracer hydroxystilbamidine. Optimization of the trajectory of the ET-1 injection needle provided excellent survival rate. MR imaging visualized the white matter injury 2 days after surgery. Motor function deficit appeared temporarily after the operation. Histological studies confirmed damage of axons and myelin sheaths followed by inflammatory reaction and gliosis similar to lacunar infarction, with lesion volume of less than 1% of the whole brain. Hydroxystilbamidine injected into the lesion revealed wide spatial distribution of the affected neuronal population. Compared with prior ET-1 injection models, this method induced standardized amount of white matter damage and temporary motor function deficit in a reproducible and safe manner. The present model is valuable for studying the pathophysiology of not only ischemia, but a broader set of white matter damage conditions in the lissencephalic brain.

  19. The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection.

    Science.gov (United States)

    Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

    2015-01-01

    The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity.

  20. The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

    Science.gov (United States)

    Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

    2015-01-01

    The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

  1. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    Science.gov (United States)

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  2. The value of diffusion tensor imaging in the differential diagnosis of subcortical ischemic vascular dementia and Alzheimer's disease in patients with only mild white matter alterations on T2-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jian-Liang; Zhang, Ting (Dept. of Neurology, Shanghai Jiaotong Univ. Affiliated Sixth People' s Hospital, Shanghai (China)); Chang, Cheng; Zhang, Yu-Zhen; Li, Wen-Bin (Inst. of Diagnostic and Interventional Radiology, Shanghai Jiaotong Univ. Affiliated Sixth People' s Hospital, Shanghai (China)), Email: liwenbin@sh163.net

    2012-04-15

    Background: Diffusion tensor imaging (DTI) is a form of functional magnetic resonance imaging (MRI) that allows examination of the microstructural integrity of white matter in the brain. Dementia is a neurodegenerative disease, and DTI can provide indirect insights of the microstructural characteristics of brains in individuals with different forms of dementia. Purpose: To evaluate the value of DTI in the diagnosis and differential diagnosis of patients with subcortical ischemic vascular dementia (SIVD) and Alzheimer's disease (AD). Material and Methods: The study included 40 patients (20 AD patients and 20 SIVD patients) and 20 normal controls (NC). After routine MRI and DTI, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured and compared in regions of interest (ROI). Results: Compared to NC and AD patients, SIVD patients had lower FA values and higher ADC values in the inferior-fronto-occipital fascicles (IFOF), genu of the corpus callosum (GCC), splenium of the corpus callosum (SCC), and superior longitudinal fasciculus (SLF). Compared to controls and SIVD patients, AD patients had lower FA values in the anterior frontal lobe, temporal lobe, hippocampus, IFOF, GCC, and CF; and higher ADC values in the temporal lobe and hippocampus. Conclusion: DTI can be used to estimate the white matter impairment in dementia patients. There were significant regional reductions of FA values and heightened ADC values in multiple regions in SIVD patients compared to AD patients. When compared with conventional MRI, DTI may provide a more objective method for the differential diagnosis of SIVD and AD disease patients who have only mild white matter alterations on T2-weighted imaging

  3. Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions.

    Science.gov (United States)

    Ruggieri, Martino; Roggini, Mario; Spalice, Alberto; Addis, Maria; Iannetti, Paola

    2009-05-01

    A 10-year-old boy presented with a severe and diffuse mosaic skin hypopigmentation running (in narrow bands) along the lines of Blaschko associated with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia, bilateral punctate cataract, microretrognathia, short neck, pectus excavatum, joint hypermobility, mild muscular hypotonia, generalized seizures, and mild mental retardation. Cranial magnetic resonance imaging revealed hypoplastic corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse subcortical, periventricular cystic-like lesions. Similar dysmorphic features were observed in the child's mother, but with no imaging abnormalities. The facial phenotype coupled with the cysts in the brain was strongly reminiscent of the oculocerebrorenal Lowe syndrome. Full chromosome studies in the parents and the proband and mutation analysis on peripheral blood lymphocytes (and on skin cultured fibroblasts from affected and unaffected skin areas in the child) in the genes for subcortical band heterotopia (DCX (Xq22.3-q23)], lissencephaly (PAFAH1B1, alias LIS1, at 17p13.3), and oculocerebrorenal syndrome of Lowe (OCRL at Xq23-q24)] were unrevealing. This constellation of multiple congenital anomalies including skin hypopigmentation and eye, musculoskeletal, and nervous system abnormalities was sufficiently characterized to be regarded as a novel example of pigmentary mosaicism of the Ito type (i.e., hypomelanosis of Ito).

  4. Clinical characteristics in subcortical ischemic white matter disease Características clínicas na doença isquêmica da substância branca subcortical

    Directory of Open Access Journals (Sweden)

    Gilberto Sousa Alves

    2009-06-01

    Full Text Available BACKGROUND: Vascular white matter lesions (WML represent one of the main neuroimage findings in individuals older than 65 years and its clinical significance is still partially understood. OBJECTIVE: To describe and analyze the clinical profile of a high severity sample with WML focusing on the frontal executive control. METHOD: Outpatients (n=20 with high severity WML evaluated with magnetic resonance imaging were selected using the Fazekas scale. RESULTS: Most patients (n=17; 85% presented an altered Trail Making Test ratio (section B/section A; on verbal fluency, 15 individuals (75% performed below the cutoff score. Apathy (5.9 ± 4.65 and depression (3.05±3.67 were frequent as assessed by the Neuropsychiatric Inventory. The impairment in functional activities strongly correlated with apathy (r=0.814, pFUNDAMENTO: Lesões vasculares em substância branca (LSB são um dos principais achados de neuroimagem em indivíduos acima de 65 anos e sua importância em termos clínicos é ainda parcialmente conhecida. OBJETIVO: Descrever e analisar o perfil clínico de amostra com LSB grave enfocando as alterações do controle executivo frontal. MÉTODO: Pacientes ambulatoriais (n=20 avaliados pela ressonância nuclear magnética e com maior proporção de LSB foram selecionados através da escala de Fazekas. RESULTADOS: A maioria dos pacientes (n=17; 85% apresentou alteração na proporção teste das trilhas (seção B/A; na fluência verbal, 15 indivíduos (75% apresentaram desempenho abaixo do ponto de corte. Apatia (5,9±4,65 e depressão (3,05±3,67 foram freqüentes na avaliação pelo Inventário Neuropsiquiátrico. O prejuízo nas atividades funcionais correlacionou-se fortemente à apatia (r=0, 814, p<0,001 e à fluência verbal (r=0, 744, p< 0,001. CONCLUSÃO: Disfunção executiva, apatia e depressão foram as principais características encontradas. A extensão e localização das LSB parecem exercer um impacto distinto nas manifesta

  5. Vanishing White Matter Disease

    Science.gov (United States)

    ... In Memory Of Obituaries Contact Us Donate Vanishing White Matter Disease What is Vanishing White Matter Disease? ... of the genetic basis of VWM was a great step forward. First of all, it allows genetic ...

  6. Grey and white matter correlates of picture naming: evidence from a voxel-based lesion analysis of the Boston Naming Test.

    Science.gov (United States)

    Baldo, Juliana V; Arévalo, Analía; Patterson, Janet P; Dronkers, Nina F

    2013-03-01

    A number of recent studies utilizing both functional neuroimaging and lesion analysis techniques in neurologic patients have produced conflicting results with respect to the neural correlates of picture naming. Picture naming involves a number of cognitive processes, from visual perception/recognition to lexical-semantic retrieval to articulation. This middle process, the ability to retrieve a name associated with an object, has been attributed in some cases to posterior portions of the left lateral temporal lobe and in other cases, to anterior temporal cortex. In the current study, we used voxel-based lesion symptom mapping (VLSM) to identify neural correlates of picture naming in a large sample of well-characterized left hemisphere (LH) patients suffering from a range of naming deficits. We tested patients on the Boston Naming Test (BNT), a clinical, standardized measure of picture naming that is widely used in both clinical and research settings. We found that overall performance on the BNT was associated with a network of LH regions that included significant portions of the left anterior to posterior middle temporal gyrus (MTG) and superior temporal gyrus (STG) and underlying white matter, and extended into left inferior parietal cortex. However, when we added covariates to this analysis that controlled for deficits in visual recognition and motor speech in order to isolate brain regions specific to lexical-semantic retrieval, the significant regions that remained were confined almost exclusively to the left mid-posterior MTG and underlying white matter. These findings support the notion that a large network in left peri-Sylvian cortex supports picture naming, but that the left mid-posterior MTG and underlying white matter play a critical role in the core ability to retrieve a name associated with an object or picture. Published by Elsevier Ltd.

  7. Metabolic Patterns in Chronic Multiple Sclerosis Lesions and Normal-appearing White Matter: Intraindividual Comparison by Using 2D MR Spectroscopic Imaging.

    Science.gov (United States)

    Fleischer, Vinzenz; Kolb, Rupert; Groppa, Sergiu; Zipp, Frauke; Klose, Uwe; Gröger, Adriane

    2016-11-01

    Purpose To perform a direct metabolic comparison of chronic lesions and diffusely injured normal-appearing white matter (NAWM) in multiple sclerosis (MS). Materials and Methods In this institutional review board-approved study, with the written informed consent of all patients, two-dimensional magnetic resonance spectroscopic imaging data in 46 patients with relapsing-remitting MS (median disease duration, 0.8 year) were analyzed by using the spectral quantification tool LCModel. Metabolic patterns were evaluated for non-gadolinium-enhancing chronic lesions and the corresponding contralateral NAWM. The sensitivity of the method was assessed by reproducing the known metabolic differences between cortical gray matter (GM) and NAWM. In addition to individual spectra, averaged spectra were calculated by accumulating free induction decays over all subjects to yield an increased signal-to-noise ratio (SNR), and in turn, to allow improved curve fitting as demonstrated by lower error bounds for low-concentration metabolites. Metabolite concentrations were statistically tested for intraindividual differences (paired t tests) to avoid effects resulting from variations in disease severity or treatment. Results Differences between the metabolite concentrations in the NAWM and the cortical GM were highly significant (P concentrations showed only slight differences (P > .07). Owing to increased SNRs in the averaged spectra compared with individual spectra (eg, for chronic lesions, 63 vs 28.4 ± 4.1), it was possible to reliably (Cramér-Rao lower bound [CRLB], white matter lesions, even very early in the disease course, further supporting the view that such lesions may not be as relevant as widely assumed. © RSNA, 2016.

  8. Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

    Science.gov (United States)

    Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

    2015-01-01

    To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

  9. Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

    Science.gov (United States)

    Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

    2015-01-01

    Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

  10. Automated, quantitative measures of grey and white matter lesion burden correlates with motor and cognitive function in children with unilateral cerebral palsy.

    Science.gov (United States)

    Pagnozzi, Alex M; Dowson, Nicholas; Doecke, James; Fiori, Simona; Bradley, Andrew P; Boyd, Roslyn N; Rose, Stephen

    2016-01-01

    White and grey matter lesions are the most prevalent type of injury observable in the Magnetic Resonance Images (MRIs) of children with cerebral palsy (CP). Previous studies investigating the impact of lesions in children with CP have been qualitative, limited by the lack of automated segmentation approaches in this setting. As a result, the quantitative relationship between lesion burden has yet to be established. In this study, we perform automatic lesion segmentation on a large cohort of data (107 children with unilateral CP and 18 healthy children) with a new, validated method for segmenting both white matter (WM) and grey matter (GM) lesions. The method has better accuracy (94%) than the best current methods (73%), and only requires standard structural MRI sequences. Anatomical lesion burdens most predictive of clinical scores of motor, cognitive, visual and communicative function were identified using the Least Absolute Shrinkage and Selection operator (LASSO). The improved segmentations enabled identification of significant correlations between regional lesion burden and clinical performance, which conform to known structure-function relationships. Model performance was validated in an independent test set, with significant correlations observed for both WM and GM regional lesion burden with motor function (p < 0.008), and between WM and GM lesions alone with cognitive and visual function respectively (p < 0.008). The significant correlation of GM lesions with functional outcome highlights the serious implications GM lesions, in addition to WM lesions, have for prognosis, and the utility of structural MRI alone for quantifying lesion burden and planning therapy interventions.

  11. Automated, quantitative measures of grey and white matter lesion burden correlates with motor and cognitive function in children with unilateral cerebral palsy

    Directory of Open Access Journals (Sweden)

    Alex M. Pagnozzi

    2016-01-01

    Full Text Available White and grey matter lesions are the most prevalent type of injury observable in the Magnetic Resonance Images (MRIs of children with cerebral palsy (CP. Previous studies investigating the impact of lesions in children with CP have been qualitative, limited by the lack of automated segmentation approaches in this setting. As a result, the quantitative relationship between lesion burden has yet to be established. In this study, we perform automatic lesion segmentation on a large cohort of data (107 children with unilateral CP and 18 healthy children with a new, validated method for segmenting both white matter (WM and grey matter (GM lesions. The method has better accuracy (94% than the best current methods (73%, and only requires standard structural MRI sequences. Anatomical lesion burdens most predictive of clinical scores of motor, cognitive, visual and communicative function were identified using the Least Absolute Shrinkage and Selection operator (LASSO. The improved segmentations enabled identification of significant correlations between regional lesion burden and clinical performance, which conform to known structure-function relationships. Model performance was validated in an independent test set, with significant correlations observed for both WM and GM regional lesion burden with motor function (p < 0.008, and between WM and GM lesions alone with cognitive and visual function respectively (p < 0.008. The significant correlation of GM lesions with functional outcome highlights the serious implications GM lesions, in addition to WM lesions, have for prognosis, and the utility of structural MRI alone for quantifying lesion burden and planning therapy interventions.

  12. Volumetric analyses of cerebral white matter hyperintensity lesions on magnetic resonance imaging in a Japanese population undergoing medical check-up.

    Science.gov (United States)

    Honda, Yuko; Noguchi, Akio; Maruyama, Keisuke; Tamura, Akira; Saito, Isamu; Sei, Kazumi; Soga, Takamasa; Ushiba, Katsuaki; Hirano, Teruyuki; Sakurai, Takashi; Shiokawa, Yoshiaki

    2015-12-01

    To clarify growth patterns, spatial distribution and risk factors of cerebral white matter hyperintensity (WMH) lesions on magnetic resonance imaging. We analyzed volumes of cerebral WMH lesions in those who underwent brain magnetic resonance imaging as a hospital-based health check-up in 2012 and 2013 by using a computational quantitative image analysis software (Software for NeuroImage Processing in Experimental Research). After excluding subjects not suitable for volumetric analyses because of pathological brain conditions, a total of 1047 healthy participants (mean age 56.6 years) were included for the analyses. First, the relationship of computational volumetry and conventional qualitative visual evaluation by Shinohara grading was evaluated. Volumes of WMH lesions were analyzed according to age and the different cerebral lobes. Finally, clinical risk factors associated with WMH lesions were assessed. Volumes of WMH lesions were significantly correlated with Shinohara grading (P aging (P aged 50 years or older. Age and systolic blood pressure were significantly related to volumes of WMH lesions in all the lobes, whereas diastolic blood pressure was not related only in the occipital lobe. Based on computational quantitative volumetric analyses, cerebral WMH lesions increased with age, and were associated with blood pressure. However, the occipital lobe was the only exception to these findings. © 2015 Japan Geriatrics Society.

  13. Reliability of quantifying vascular white matter brain lesions - a contribution to reproducible quantitative diagnosis; Reliabilitaet der Quantifizierung von vaskulaeren Laesionen der weissen Hirnsubstanz - ein Beitrag zur replizierbaren quantitativen Diagnostik

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    Hentschel, F.; Kreis, M.; Damian, M. [Abt. Neuroradiologie, ZI, Fakultaet fuer klinische Medizin Mannheim der Univ. Heidelberg (Germany); Diepers, M. [Abt. Neuroradiologie des Universitaetsklinikums Mannheim (Germany); Disque, C.; Dzialowski, I.; Kitzler, H.; Rodewald, A. [Abt. Neuroradiologie des Universitaetsklinikums Dresden (Germany); Struffert, T. [Abt. Neuroradiologie des Universitaetsklinikums Homburg (Germany); Trittmacher, S. [Abt. Neuroradiologie des Universitaetsklinikums Giessen (Germany); Wille, P.R. [Inst. fuer Neuroradiologie der Univ. Mainz (Germany); Krumm, B. [Abt. Biostatistik, ZI, Fakultaet fuer klinische Medizin Mannheim der Univ. Heidelberg (Germany)

    2005-01-01

    Purpose: microangiopathic lesions of the brain tissue correlate with the clinical diagnosis of vascular subcortical dementia. The ''experience-based'' evaluation is insufficient. Rating scales may contribute to reproducible quantification. Materials and methods: in MRI studies of 10 patients, 9 neuroradiologists quantified vascular white matter lesions (WMLs) at two different points in time for 12 anatomically defined regions with respect to number, size and localization (score). For 9 observers and 10 studies, 90 intra-observer differences were obtained for each of the 12 WML scores. To calculate the inter-observer reliability, rating pairs were formed. Furthermore, 360 differences were computed for each score and rating for 12 anatomically defined WML scores, and the intraclass correlation (ICC) was calculated as a measure of agreement (reliability). Results: as to the intra-observer reliability, the median of the differences was 1.5 for the entire brain as opposed to 0 for defined brain regions. The corresponding values for the inter-observer reliability were 3 and 1, respectively. The mean intra-class correlation coefficient for the 10 studies was 0.88, whereas the mean interclass correlation concerning the inter-observer reliability was 0.70, with the first and second rating being averaged. The rating of each study took about 6 minutes. Conclusion: the rating scale with high intra- and inter-observer reliability can dependably quantify WMLs and correlates with the clinical diagnosis of vascular dementia. Using a reliable rating scale, the diagnostic distinction of age - associated physiological vs. pathological size of the NMC can make a contribution to the reproducible quantifiable diagnostic evaluation of vascular brain tissue lesions within the framework of dementia diagnostics. (orig.)

  14. Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

    Science.gov (United States)

    Ramirez, J; Gibson, E; Quddus, A; Lobaugh, N J; Feinstein, A; Levine, B; Scott, C J M; Levy-Cooperman, N; Gao, F Q; Black, S E

    2011-01-15

    Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. White matter tract recovery following medial temporal lobectomy and selective amygdalohippocampectomy for tumor resection via a ROVOT-m port-guided technique: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Srikant S. Chakravarthi

    2016-12-01

    Conclusions: To our knowledge, this is the first reported case of a temporal lobectomy and amygdalohippocampectomy using a port technique, in particular, one that demonstrates recovery of the critical (ILF and uncinate fasciculus subcortical white matter tracts. The combination of real-time, rapid, geometrically accurate 3D-planning of white matter tracts is imperative, especially in conjunction with minimally invasive approaches, thereby offering a new, safer perspective into the approach of temporal lobe lesions.

  16. White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70-year-olds followed over 10 years.

    Science.gov (United States)

    Gudmundsson, P; Olesen, P J; Simoni, M; Pantoni, L; Östling, S; Kern, S; Guo, X; Skoog, I

    2015-05-01

    A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population. Whether WMLs and cortical atrophy on computed tomography predict dementia and depression was investigated in a population-based sample of 70-year-olds (n = 380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini-Mental State Examination score below 26 at baseline in 2000-2001. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary outcomes included dementia and major depression at 10-year follow-up. Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.23-12.76] and temporal lobe atrophy (OR 2.93, 95% CI 1.13-7.60) predicted dementia during a 10-year follow-up independently of major depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25-11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06-5.96) predicted depression even after controlling for incident dementia. White matter lesions and temporal lobe atrophy preceded 10-year incidence of both dementia and depression in 70-year-olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults. © 2015 EAN.

  17. Role of white matter lesions, cerebral atrophy, and APOE on cognition in older persons with and without dementia: the Cache County, Utah, study of memory and aging.

    Science.gov (United States)

    Bigler, Erin D; Lowry, Christopher M; Kerr, Burton; Tate, David F; Hessel, Cory D; Earl, Heath D; Miller, Michael J; Rice, Sara A; Smith, Kay H; Tschanz, JoAnn T; Welsh-Bohmer, Kathleen; Plassman, Brenda; Victoroff, Jeff

    2003-07-01

    Neuropsychological, qualitative, and quantitative magnetic resonance imaging findings were examined in subjects with Alzheimer's disease (AD), non-AD dementia or mixed neuropsychiatric disorder, subjects characterized as mild/ambiguous, and controls, all with known apolipoprotein E (APOE) genotype. Neuropsychological tasks included an expanded Consortium to Establish a Registery for Alzheimer's Disease (J. T. Tschanz et al., 2000; K. A. Welsh, J. M. Hoffman, N. L. Earl, & M. W. Hanson 1994) battery and the Mini-Mental Status Examination (M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975). Periventricular white matter lesions were the most clinically salient, and generalized measures of cerebral atrophy were the most significant quantitative indicators. APOE genotype was unrelated to imaging or neuropsychological performance. Neuropsychological relationships with neuroimaging findings depend on the qualitative or quantitative method used.

  18. Common behavioral clusters and subcortical anatomy in stroke

    Science.gov (United States)

    Corbetta, Maurizio; Ramsey, Lenny; Callejas, Alicia; Baldassarre, Antonello; Hacker, Carl D.; Siegel, Joshua S.; Astafiev, Serguei V.; Rengachary, Jennifer; Zinn, Kristina; Lang, Catherine E.; Connor, Lisa Tabor; Fucetola, Robert; Strube, Michael; Carter, Alex R.; Shulman, Gordon L.

    2015-01-01

    SUMMARY A long-held view is that stroke causes many distinct neurological syndromes due to damage of specialized cortical and subcortical centers. However, it is unknown if a syndrome-based description is helpful in characterizing behavioral deficits across a large number of patients. We studied a large prospective sample of first-time stroke patients with heterogeneous lesions at 1–2 weeks post-stroke. We measured behavior over multiple domains and lesion anatomy with structural MRI and a probabilistic atlas of white matter pathways. Multivariate methods estimated the percentage of behavioral variance explained by structural damage. A few clusters of behavioral deficits spanning multiple functions explained neurological impairment. Stroke topography was predominantly subcortical, and disconnection of white matter tracts critically contributed to behavioral deficits and their correlation. The locus of damage explained more variance for motor and language than memory or attention deficits. Our findings highlight the need for better models of white matter damage on cognition. PMID:25741721

  19. Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

    NARCIS (Netherlands)

    Ederle, J.; Davagnanam, I.; Worp, H.B. van der; Venables, G.S.; Lyrer, P.A.; Featherstone, R.L.; Brown, M.M.; Jager, H.R.; Leeuw, F.E. de; Schultze Kool, L.J.; Vliet, J.A. van der

    2013-01-01

    BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid

  20. Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

    NARCIS (Netherlands)

    Ederle, Jörg; Davagnanam, Indran; van der Worp, H. Bart; Venables, Graham S.; Lyrer, Philippe A.; Featherstone, Roland L.; Brown, Martin M.; Jäger, H. Rolf; Algra, A.; Bamford, J.; Beard, J.; Bland, M.; Bradbury, A. W.; Brown, M. M.; Clifton, A.; Gaines, P.; Hacke, W.; Halliday, A.; Malik, I.; Mas, J. L.; McGuire, A. J.; Sidhu, P.; Venables, G.; Bradbury, A.; Collins, R.; Molyneux, A.; Naylor, R.; Warlow, C.; Ferro, J. M.; Thomas, D.; Bonati, L. H.; Coward, L.; Dobson, J.; Ederle, J.; Featherstone, R. F.; Tindall, H.; McCabe, D. J. H.; Wallis, A.; Brooks, M.; Chambers, B.; Chan, A.; Chu, P.; Clark, D.; Dewey, H.; Donnan, G.; Fell, G.; Hoare, M.; Molan, M.; Roberts, A.; Roberts, N.; Beiles, B.; Bladin, C.; Clifford, C.; Grigg, M.; New, G.; Bell, R.; Bower, S.; Chong, W.; Holt, M.; Saunder, A.; Than, P. G.; Gett, S.; Leggett, D.; McGahan, T.; Quinn, J.; Ray, M.; Wong, A.; Woodruff, P.; Foreman, R.; Schultz, D.; Scroop, R.; Stanley, B.; Allard, B.; Atkinson, N.; Cambell, W.; Davies, S.; Field, P.; Milne, P.; Mitchell, P.; Tress, B.; Yan, B.; Beasley, A.; Dunbabin, D.; Stary, D.; Walker, S.; Cras, P.; d'Archambeau, O.; Hendriks, J. M. H.; van Schil, P.; Bosiers, M.; Deloose, K.; van Buggenhout, E.; de Letter, J.; Devos, V.; Ghekiere, J.; Vanhooren, G.; Astarci, P.; Hammer, F.; Lacroix, V.; Peeters, A.; Verhelst, R.; DeJaegher, L.; Verbist, J.; Blair, J.-F.; Caron, J. L.; Daneault, N.; Giroux, M.-F.; Guilbert, F.; Lanthier, S.; Lebrun, L.-H.; Oliva, V.; Raymond, J.; Roy, D.; Soulez, G.; Weill, A.; Hill, M.; Hu, W.; Hudion, M.; Morrish, W.; Sutherland, G.; Wong, J.; Albäck, A.; Harno, H.; Ijäs, P.; Kaste, M.; Lepäntalo, M.; Mustanoja, S.; Paananen, T.; Porras, M.; Putaala, J.; Railo, M.; Sairanen, T.; Soinne, L.; Vehmas, A.; Vikatmaa, P.; Goertler, M.; Halloul, Z.; Skalej, M.; Brennan, P.; Kelly, C.; Leahy, A.; Moroney, J.; Thornton, J.; Koelemay, M. J. W.; Nederkoorn, P. J.; Reekers, J. A. A.; Roos, Y. B. W. E. M.; Hendriks, J. M.; Koudstaal, P. J.; Pattynama, P. M. T.; van der Lugt, A.; van Dijk, L. C.; van Sambeek, M. R. H. M.; van Urk, H.; Verhagen, H. J. M.; Bruijninckx, C. M. A.; de Bruijn, S. F.; Keunen, R.; Knippenberg, B.; Mosch, A.; Treurniet, F.; van Dijk, L.; van Overhagen, H.; Wever, J.; de Beer, F. C.; van den Berg, J. S. P.; van Hasselt, B. A. A. M.; Zeilstra, D. J.; Boiten, J.; de Mol van Otterloo, J. C. A.; de Vries, A. C.; Lycklama a Nijeholt, G. J.; van der Kallen, B. F. W.; Blankensteijn, J. D.; de Leeuw, F. E.; Schultze Kool, L. J.; van der Vliet, J. A.; de Borst, G. J.; de Kort, G. A. P.; Kapelle, L. J.; Lo, T. H.; Mali, W. P. Th M.; Moll, F.; van der Worp, H. B.; Verhagen, H.; Barber, P. A.; Bourchier, R.; Hill, A.; Holden, A.; Stewart, J.; Bakke, S. J.; Krohg-Sørensen, K.; Skjelland, M.; Tennøe, B.; Bialek, P.; Biejat, Z.; Czepiel, W.; Czlonkowska, A.; Dowzenko, A.; Jedrzejewska, J.; Kobayashi, A.; Lelek, M.; Polanski, J.; Kirbis, J.; Milosevic, Z.; Zvan, B.; Blasco, J.; Chamorro, A.; Macho, J.; Obach, V.; Riambau, V.; San Roman, L.; Branera, J.; Canovas, D.; Estela, Jordi; Gimenez Gaibar, A.; Perendreu, J.; Björses, K.; Gottsater, A.; Ivancev, K.; Maetzsch, T.; Sonesson, B.; Berg, B.; Delle, M.; Formgren, J.; Gillgren, P.; Kall, T.-B.; Konrad, P.; Nyman, N.; Takolander, R.; Andersson, T.; Malmstedt, J.; Soderman, M.; Wahlgren, C.; Wahlgren, N.; Binaghi, S.; Hirt, L.; Michel, P.; Ruchat, P.; Engelter, S. T.; Fluri, F.; Guerke, L.; Jacob, A. L.; Kirsch, E.; Lyrer, P. A.; Radue, E.-W.; Stierli, P.; Wasner, M.; Wetzel, S.; Bonvin, C.; Kalangos, A.; Lovblad, K.; Murith, N.; Ruefenacht, D.; Sztajzel, R.; Higgins, N.; Kirkpatrick, P. J.; Martin, P.; Varty, K.; Adam, D.; Bell, J.; Crowe, P.; Gannon, M.; Henderson, M. J.; Sandler, D.; Shinton, R. A.; Scriven, J. M.; Wilmink, T.; D'Souza, S.; Egun, A.; Guta, R.; Punekar, S.; Seriki, D. M.; Thomson, G.; Brennan, J. A.; Enevoldson, T. P.; Gilling-Smith, G.; Gould, D. A.; Harris, P. L.; McWilliams, R. G.; Nasser, H.-C.; White, R.; Prakash, K. G.; Serracino-Inglott, F.; Subramanian, G.; Symth, J. V.; Walker, M. G.; Clarke, M.; Davis, M.; Dixit, S. A.; Dorman, P.; Dyker, A.; Ford, G.; Golkar, A.; Jackson, R.; Jayakrishnan, V.; Lambert, D.; Lees, T.; Louw, S.; Macdonald, S.; Mendelow, A. D.; Rodgers, H.; Rose, J.; Stansby, G.; Wyatt, M.; Baker, T.; Baldwin, N.; Jones, L.; Mitchell, D.; Munro, E.; Thornton, M.; Baker, D.; Davis, N.; Hamilton, G.; McCabe, D.; Platts, A.; Tibballs, J.; Cleveland, T.; Dodd, D.; Lonsdale, R.; Nair, R.; Nassef, A.; Nawaz, S.; Belli, A.; Cloud, G.; Markus, H.; McFarland, R.; Morgan, R.; Pereira, A.; Thompson, A.; Chataway, J.; Cheshire, N.; Gibbs, R.; Hammady, M.; Jenkins, M.; Wolfe, J.; Adiseshiah, M.; Bishop, C.; Brew, S.; Brookes, J.; Jäger, R.; Kitchen, N.; Ashleigh, R.; Butterfield, S.; Gamble, G. E.; McCollum, C.; Nasim, A.; O'Neill, P.; Edwards, R. D.; Lees, K. R.; MacKay, A. J.; Moss, J.; Rogers, P.

    2013-01-01

    Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.

  1. White matter involvement in sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Caverzasi, Eduardo; Mandelli, Maria Luisa; DeArmond, Stephen J; Hess, Christopher P; Vitali, Paolo; Papinutto, Nico; Oehler, Abby; Miller, Bruce L; Lobach, Irina V; Bastianello, Stefano; Geschwind, Michael D; Henry, Roland G

    2014-12-01

    Sporadic Creutzfeldt-Jakob disease is considered primarily a disease of grey matter, although the extent of white matter involvement has not been well described. We used diffusion tensor imaging to study the white matter in sporadic Creutzfeldt-Jakob disease compared to healthy control subjects and to correlated magnetic resonance imaging findings with histopathology. Twenty-six patients with sporadic Creutzfeldt-Jakob disease and nine age- and gender-matched healthy control subjects underwent volumetric T1-weighted and diffusion tensor imaging. Six patients had post-mortem brain analysis available for assessment of neuropathological findings associated with prion disease. Parcellation of the subcortical white matter was performed on 3D T1-weighted volumes using Freesurfer. Diffusion tensor imaging maps were calculated and transformed to the 3D-T1 space; the average value for each diffusion metric was calculated in the total white matter and in regional volumes of interest. Tract-based spatial statistics analysis was also performed to investigate the deeper white matter tracts. There was a significant reduction of mean (P=0.002), axial (P=0.0003) and radial (P=0.0134) diffusivities in the total white matter in sporadic Creutzfeldt-Jakob disease. Mean diffusivity was significantly lower in most white matter volumes of interest (Pchanges in white matter anisotropy. Tract-based spatial statistics analysis showed significant reductions of mean diffusivity within the white matter of patients with sporadic Creutzfeldt-Jakob disease, mainly in the left hemisphere, with a strong trend (P=0.06) towards reduced mean diffusivity in most of the white matter bilaterally. In contrast, by visual assessment there was no white matter abnormality either on T2-weighted or diffusion-weighted images. Widespread reduction in white matter mean diffusivity, however, was apparent visibly on the quantitative attenuation coefficient maps compared to healthy control subjects

  2. A case of generalized auditory agnosia with unilateral subcortical brain lesion.

    Science.gov (United States)

    Suh, Hyee; Shin, Yong-Il; Kim, Soo Yeon; Kim, Sook Hee; Chang, Jae Hyeok; Shin, Yong Beom; Ko, Hyun-Yoon

    2012-12-01

    The mechanisms and functional anatomy underlying the early stages of speech perception are still not well understood. Auditory agnosia is a deficit of auditory object processing defined as a disability to recognize spoken languages and/or nonverbal environmental sounds and music despite adequate hearing while spontaneous speech, reading and writing are preserved. Usually, either the bilateral or unilateral temporal lobe, especially the transverse gyral lesions, are responsible for auditory agnosia. Subcortical lesions without cortical damage rarely causes auditory agnosia. We present a 73-year-old right-handed male with generalized auditory agnosia caused by a unilateral subcortical lesion. He was not able to repeat or dictate but to perform fluent and comprehensible speech. He could understand and read written words and phrases. His auditory brainstem evoked potential and audiometry were intact. This case suggested that the subcortical lesion involving unilateral acoustic radiation could cause generalized auditory agnosia.

  3. Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): Assessment of the involved white matter tracts by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kassem, Hassan [Department of Radiology, Benha University (Egypt); Wafaie, Ahmed, E-mail: a_wafaie@yahoo.com [Department of Radiology, Cairo University (Egypt); Abdelfattah, Sherif [Department of Radiology, Cairo University (Egypt); Farid, Tarek [Pediatric Department, Egyptian National Research Center (Egypt)

    2014-01-15

    Background and purpose: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. Patients and methods: We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy ({sup 1}H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. Results: In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable

  4. A Patient with Fragile X-Associated Tremor/Ataxia Syndrome Presenting with Executive Cognitive Deficits and Cerebral White Matter Lesions

    Directory of Open Access Journals (Sweden)

    Kensaku Kasuga

    2011-05-01

    Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a late-onset neurodegenerative disorder that primarily affects males who are carriers of a premutation of a CGG expansion in the FMR1 gene. In Asian populations, FXTAS has rarely been reported. Here, we report the case of a Japanese FXTAS patient who showed predominant executive cognitive deficits as the main feature of his disease. In contrast, the patient exhibited only very mild symptoms of intention tremor and ataxia, which did not interfere with daily activities. A gene analysis revealed that the patient carried a premutation of a CGG expansion (111 CGG repeats in the FMR1 gene. The mRNA expression level of FMR1 in the patient was 1.5-fold higher than in controls. On brain MRI scans, fluid-attenuated inversion recovery images showed high-intensity lesions in the middle cerebellar peduncles and the cerebral white matter, with a frontal predominance. The present case extends previous notions regarding the cognitive impairment in FXTAS patients. Recognizing FXTAS patients with predominant cognitive impairment from various ethnic backgrounds would contribute to our understanding of the phenotypic variation of this disease.

  5. Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

    2017-10-01

    To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

  6. Impact of White Matter Lesions on Cognition in Stroke Patients Free from Pre-Stroke Cognitive Impairment: A One-Year Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Hege Ihle-Hansen

    2012-03-01

    Full Text Available Background/Aim: Post-stroke cognitive impairment and dementia may be caused by pure vascular, pure degenerative or mixed disease. The relation between post-stroke cognitive impairment and the combination of vascular pathology and degenerative changes is less evaluated. We aimed to evaluate the associations between white matter lesions (WMLs and patient performance 1 year after stroke on tests of executive functioning, memory and visuospatial function, adjusted for the effects of lifestyle and disease-related factors, including medial temporal lobe atrophy (MTLA. Methods: Patients with a first-ever stroke or transient ischemic attack were invited to participate in the study. The associations between the cognitive test performances and WMLs were studied using linear regression [Trail Making Test B (TMT B and 10-word test] and logistic regression (Clock Drawing Test. Results: In total, 199 patients completed the follow-up. The TMT B (p = 0.029 and the 10-word test (p = 0.014 were significantly associated with WMLs; however, the Clock Drawing Test (p = 0.19 was not. The TMT B (p = 0.018 and the 10-word test (p ≤ 0.001 were both significantly associated with MTLA. Conclusion: Impaired executive functioning and memory are significantly associated with WMLs and MTLA. The mechanisms explaining post-stroke cognitive impairment are multifactorial, including different types of vascular pathology and coexisting vascular and degenerative changes.

  7. White matter lesion load is associated with resting state functional MRI activity and amyloid PET but not FDG in mild cognitive impairment and early Alzheimer's disease patients.

    Science.gov (United States)

    Zhou, Yongxia; Yu, Fang; Duong, Timothy Q

    2015-01-01

    To quantify and investigate the interactions between multimodal MRI/positron emission tomography (PET) imaging metrics in elderly patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. Thirteen early AD, 17 MCI patients, and 14 age-matched healthy aging controls from the Alzheimer's Disease Neuroimaging Initiative database were selected based on availability of data. Default mode network (DMN) functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) were obtained for resting state functional MRI (RS-fMRI). White matter lesion load (WMLL) was quantified from MRI T2-weighted FLAIR images. Amyloid deposition with PET [(18)F]-Florbetapir tracer and metabolism of glucose by means of [(18)F]-fluoro-2-deoxyglucose (FDG) images were quantified using ratio of standard uptake values (rSUV). Whole-brain WMLL and amyloid deposition were significantly higher (P functional activity and PET amyloid load suggest the potential of MRI and PET-based biomarkers for early detection of AD. © 2013 Wiley Periodicals, Inc.

  8. The relationship between right-to-left shunt and brain white matter lesions in Japanese patients with migraine: a single center study.

    Science.gov (United States)

    Iwasaki, Akio; Suzuki, Keisuke; Takekawa, Hidehiro; Takashima, Ryotaro; Suzuki, Ayano; Suzuki, Shiho; Hirata, Koichi

    2017-12-01

    There may be a link between right-to-left shunt (RLs) and brain white matter lesions (WMLs) in patients with migraine. In this study, we assessed the relationship between WMLs and RLs in Japanese migraine patients. A total of 107 consecutive patients with migraine with (MA) and without aura (MWOA) were included in this study. Contrast transcranial Doppler ultrasound was used to detect RLs. WMLs were graded using brain magnetic resonance imaging based on well-established criteria. The prevalence of RLs was significantly increased in the WMLs positive group (n = 24) compared with the WMLs negative group (n = 83) (75.0% vs. 47.0%, p = 0.015). In prevalence of WMLs between MA and MWOA patients, there were no statistical differences (p = 0.410). Logistic regression analysis adjusted by age and disease duration of migraine identified an RLs-positive status as the sole determinant for the presence of WMLs (OR = 6.15; 95% CI 1.82-20.8; p = 0.003) CONCLUSION: Our study suggests a possible link between RLs and WMLs in Japanese patients with migraine.

  9. Brain white matter demyelinating lesions and amyotrophic lateral sclerosis in a patient with C9orf72 hexanucleotide repeat expansion.

    Science.gov (United States)

    Oliveira Santos, Miguel; Caldeira, Inês; Gromicho, Marta; Pronto-Laborinho, Ana; de Carvalho, Mamede

    2017-10-01

    A hexanucleotide repeat expansion in the C9orf72 gene is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. It has been described before four patients with multiple sclerosis (MS) and C9orf72-ALS. However, C9orf72 positivity is not associated with increased risk of MS. Inflammatory pathways related to NF-κB have been linked to ALS and MS, and appear to be important in C9orf72-ALS patients. A 42-year-old woman presented with progressive bulbar symptoms for 9 months. Neurological examination disclosed spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment confirmed ALS. Brain MRI revealed multiple and bilateral juxtacortical and periventricular inflammatory changes, some with gadolinium-enhancement, configuring a probable MS-like pattern. CSF evaluation was unremarkable, with no oligoclonal bands. Visual and somatosensory evoked potentials were normal. Follow-up brain MRI 6 months later showed two new lesions in two relatively characteristic locations of MS, with no gadolinium-enhancement. Genetic screening revealed a C9orf72 expansion. As patient had no clinical manifestation of MS, a diagnosis of radiologically isolated syndrome was considered. We speculate that these demyelinating lesions might facilitate expressivity of C9orf72 expansion, through NF-κB activation. This plausible association may lead to the identification of a therapeutic target in this subgroup of C9orf72-ALS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Gerstmann meets Geschwind: a crossing (or kissing) variant of a subcortical disconnection syndrome?

    Science.gov (United States)

    Kleinschmidt, Andreas; Rusconi, Elena

    2011-12-01

    That disconnection causes clinical symptoms is a very influential concept in behavioral neurology. Criteria for subcortical disconnection usually are symptoms that are distinct from those following cortical lesions and damage to a single, long-range fiber tract. Yet, a recent study combining functional magnetic resonance imaging and fiber tracking concluded that a focal lesion in left parietal white matter provides the only tenable explanation for pure Gerstmann's syndrome, an enigmatic tetrad of acalculia, agraphia, finger agnosia, and left-right disorientation. Such a lesion would affect not only a single fiber tract but crossing or "kissing" of different fiber tracts and hence disconnect separate cortical networks. As fiber crossing is prominent in the cerebral white matter, the authors propose an extension to the subcortical disconnection framework that opens the door to ascribing a more diversified clinical phenomenology to white matter damage and ensuing disconnection than has been the case so far.

  11. White matter involvement in mitochondrial diseases.

    Science.gov (United States)

    Lerman-Sagie, Tally; Leshinsky-Silver, Esther; Watemberg, Nathan; Luckman, Yehudit; Lev, Dorit

    2005-02-01

    White matter involvement is recently being realized as a common finding in mitochondrial disorders. It is considered an inherent part of the classical mitochondrial syndromes which are usually associated with alterations in the mitochondrial DNA such as: Leigh disease, Kearns-Sayre syndrome, mitochondrial encephalomyopathy lactic acidosis, and stroke like episodes, mitochondrial neuro-gastro-intestinal encephalomyopathy and Leber's hereditary optic neuropathy. White matter involvement is also described in mitochondrial disorders due to mutations in the nuclear DNA which are transmitted in an autosomal pattern. MRI findings suggestive of a mitochondrial disease are: small cyst-like lesions in abnormal white matter, involvement of both cerebral and cerebellar white matter, and a combination of a leukoencephalopathy with bilateral basal ganglia lesions. The clinical manifestations may be disproportionate to the extent of white matter involvement. Other organs may frequently be involved. The onset is often in infancy with a neurodegenerative course. The finding of a leukoencephalopathy in a patient with a complex neurologic picture and multisystem involvement should prompt a thorough mitochondrial evaluation.

  12. Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study.

    Science.gov (United States)

    Mok, Vincent C T; Lam, Wynnie W M; Fan, Yu Hua; Wong, Adrian; Ng, Ping Wing; Tsoi, Tak Hon; Yeung, Vincent; Wong, Ka Sing

    2009-05-01

    Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.

  13. Association between α-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI.

    Science.gov (United States)

    Kuriyama, Nagato; Ozaki, Etsuko; Mizuno, Toshiki; Ihara, Masafumi; Mizuno, Shigeto; Koyama, Teruhide; Matsui, Daisuke; Watanabe, Isao; Akazawa, Kentaro; Takeda, Kazuo; Takada, Akihiro; Inaba, Masaaki; Yamada, Shinsuke; Motoyama, Koka; Takeshita, Wakiko; Iwai, Komei; Hashiguchi, Kanae; Kobayashi, Daiki; Kondo, Masaki; Tamura, Aiko; Yamada, Kei; Nakagawa, Masanori; Watanabe, Yoshiyuki

    2018-01-01

    The anti-aging protein, α-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α-Klotho in the brain has not been sufficiently investigated. Here, we investigated the association between α-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α-Klotho level were retrospectively investigated. The α-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the α-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low α-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. A reduced blood α-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α-Klotho level may serve as a useful clinical index of vascular cognitive impairment.

  14. Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease

    NARCIS (Netherlands)

    Laat, K.F. de; Tuladhar, A.M.; Norden, A.G.W. van; Norris, D.G.; Zwiers, M.P.; Leeuw, F.E. de

    2011-01-01

    Gait disturbances are common in the elderly. Cerebral small vessel disease, including white matter lesions and lacunars infarcts, is thought to disrupt white matter tracts that connect important motor regions, hence resulting in gait disturbances. Pathological studies have demonstrated abnormalities

  15. Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia.

    Science.gov (United States)

    Gold, Gabriel; Kövari, Enikö; Herrmann, François R; Canuto, Alessandra; Hof, Patrick R; Michel, Jean-Pierre; Bouras, Constantin; Giannakopoulos, Panteleimon

    2005-06-01

    Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology. Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.

  16. Aging of cerebral white matter.

    Science.gov (United States)

    Liu, Huan; Yang, Yuanyuan; Xia, Yuguo; Zhu, Wen; Leak, Rehana K; Wei, Zhishuo; Wang, Jianyi; Hu, Xiaoming

    2017-03-01

    White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer's disease, and Parkinson's disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Grey-Matter Metabolism in Relation with White-Matter Lesions in Older Hypertensive Patients with Subjective Memory Complaints: A Pilot Voxel-Based Analysis Study.

    Science.gov (United States)

    Verger, Antoine; Hossu, Gabriela; Kearney-Schwartz, Anna; Bracard, Serge; Roch, Veronique; Van der Gucht, Axel; Fay, Renaud; Benetos, Athanase; Marie, Pierre-Yves; Joly, Laure

    2016-01-01

    This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging. Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images. The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy. White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy. © 2016 S. Karger AG, Basel.

  18. [Acute psychiatric pathology disclosing subcortical lesion in neuro-AIDS].

    Science.gov (United States)

    Donnet, A; Harlé, J R; Cherif, A A; Gastaut, J A; Weiller, P J

    1991-01-01

    Maccario et al. described, in 1987, the case of an HIV-positive patient whose psychotic symptomatology was the expression of right centrum semi-ovale lesion. We report the case of a patient who suffered a sudden delirium, expression of a probable right lenticular cerebral toxoplasmosis. This 35-year-old male homosexual, who had no psychiatric history, suddenly developed in November 1988 the following psychiatric signs: he started to walk back and forth incessantly, he had the impression that he was the subject of the conversations of the passers-by, that all the posters and notices refer to him, and that he was God. He was admitted in a psychiatric department where the symptoms were progressively curbed by neuroleptics (cyamemazine 75 mg, and haloperidol 15 mg). The episode was not questioned by the patient, but attributed to bad eating habits. HIV-positivity had been discovered a year later (during systematic screening). A computerized tomographic (CT) scan performed subsequently to this delirium was interpreted as normal. Four weeks later the patient was referred to us. The psychiatric condition was stabilized in spite of a certain aggressiveness and the probable persistence of an underlying delirium state. Laboratory examinations showed the following: blood count revealed leukopenia (2.2 G/l) and thrombocytopenia (135 G/l; OKT4/OKT8 ratio was 0.08; CSF: normal; sputum culture evidenced the presence of pneumocystis carinii; EEG were normal. Neuropsychological symptoms concerned in particular a lack of concentration during the different tests with a definitive wavering of attention. Lexical retrieval was poor whatever the topic proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

    Directory of Open Access Journals (Sweden)

    Samuel Neal Lockhart

    2012-03-01

    Full Text Available Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH and fractional anisotropy (FA obtained from diffusion tensor imaging, differ with aging and cerebrovascular disease and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals.

  20. Partly segregated cortico-subcortical pathways support phonologic and semantic verbal fluency: A lesion study.

    Science.gov (United States)

    Chouiter, Leila; Holmberg, Josefina; Manuel, Aurelie L; Colombo, Françoise; Clarke, Stephanie; Annoni, Jean-Marie; Spierer, Lucas

    2016-08-04

    Verbal fluency refers to the ability to generate as many words as possible in a limited time interval, without repetition and according to either a phonologic (each word begins with a given letter) or a semantic rule (each word belongs to a given semantic category). While current literature suggests the involvement of left fronto-temporal structures in fluency tasks, whether the same or distinct brain areas are necessary for each type of fluency remains unclear. We tested the hypothesis for an involvement of partly segregated cortico-subcortical structures between phonologic and semantic fluency by examining with a voxel-based lesion symptom mapping approach the effects of brain lesions on fluency scores corrected for age and education level in a group of 191 unselected brain-damaged patients with a first left or right hemispheric lesion. There was a positive correlation between the scores to the two types of fluency, suggesting that common mechanisms underlie the word generation independent of the production rule. The lesion-symptom mapping revealed that lesions to left basal ganglia impaired both types of fluency and that left superior temporal, supramarginal and rolandic operculum lesions selectively impaired phonologic fluency and left middle temporal lesions impaired semantic fluency. Our results corroborate current neurocognitive models of word retrieval and production, and refine the role of cortical-subcortical interaction in lexical search by highlighting the common executive role of basal ganglia in both types of verbal fluency and the preferential involvement of the ventral and dorsal language pathway in semantic and phonologic fluency, respectively. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Magnetic resonance imaging of white matter diseases of prematurity

    Energy Technology Data Exchange (ETDEWEB)

    Rutherford, Mary A.; Supramaniam, Veena; Ederies, Ashraf; Chew, Andrew; Anjari, Mustafa; Counsell, Serena [Imperial College, Hammersmith Hospital, Robert Steiner MR Unit, MRC Clinical Sciences Centre, London (United Kingdom); Bassi, Laura; Groppo, Michela; Ramenghi, Luca A. [University of Milan, NICU, Institute of Pediatrics and Neonatology, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan (Italy)

    2010-06-15

    Periventricular leucomalacia (PVL) and parenchymal venous infarction complicating germinal matrix/intraventricular haemorrhage have long been recognised as the two significant white matter diseases responsible for the majority of cases of cerebral palsy in survivors of preterm birth. However, more recent studies using magnetic resonance imaging to assess the preterm brain have documented two new appearances, adding to the spectrum of white matter disease of prematurity: punctate white matter lesions, and diffuse excessive high signal intensity (DEHSI). These appear to be more common than PVL but less significant in terms of their impact on individual neurodevelopment. They may, however, be associated with later cognitive and behavioural disorders known to be common following preterm birth. It remains unclear whether PVL, punctate lesions, and DEHSI represent a continuum of disorders occurring as a result of a similar injurious process to the developing white matter. This review discusses the role of MR imaging in investigating these three disorders in terms of aetiology, pathology, and outcome. (orig.)

  2. White matter of the brain

    Science.gov (United States)

    ... and Clinical Applications. 4th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 9. Ransom BR, Goldberg MP, Arai K, Baltan S. White matter pathophysiology. In: Grotta JC, Albers GW, Broderick ...

  3. White matter integrity, substance use, and risk taking in adolescence.

    Science.gov (United States)

    Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

    2013-06-01

    White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps behaviors (ΔR2 = 10%, p risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. 2013 APA, all rights reserved

  4. Frequency and pathogenesis of silent subcortical brain infarction in acute first-ever ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Tomohide; Kobayashi, Shotai; Yamaguchi, Shuhei [Shimane Medical Univ., Izumo (Japan)

    2002-02-01

    We have often observed silent subcortical brain lesions on CT or MRI in first-ever ischemic stroke, but there is little published information on the relationship of these lesions to stroke subtypes. Here, we describe the incidence of MRI-detected silent subcortical brain lesions, including infarctions and white matter lesions, in a series of patients with first-ever ischemic stroke classified according to stroke subtypes. We also discuss the pathogenesis of these silent subcortical lesions. We evaluated 171 patients with acute first-ever ischemic stroke. The subjects were divided into three groups: lacunar, atherothrombotic and cardioembolic infarction groups. We evaluated silent subcortical brain infarction (SSBI), enlargement of perivascular space (EPS), and other white-matter lesions using MRI. Hypertension was observed in 67.6% of lacunar infarction, 57.1% of atherosclerotic infarction, and 54.1% of cardioembolic infarction. SSBI was more frequently observed in lacunar infarction than the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 81.5% vs. 44.4% vs. 42.1%, p=0.006). High-grade EPS (grade 2 or higher) was also observed more frequently in lacunar infarction than in the others (lacunar vs. atherothrombotic vs. cardiogenic infarction, 63.3% vs. 24.2% vs. 0%, p<0.001). Scheltens' score of silent subcortical lesions was significantly higher in lacunar infarction than in the others. The frequency of silent subcortical ischemic brain lesions was significantly higher in lacunar infarction than in atherosclerotic or cardioembolic infarction. We suggest that the pathogenesis of silent subcortical ischemic brain lesions is common to that of lacunar infarction, that is, small-vessel vasculopathy. (author)

  5. Essential hypertension, cerebral white matter pathology and ischemic stroke.

    Science.gov (United States)

    Sierra, C

    2014-01-01

    Stroke is one of the most-frequent causes of death and the first cause of disability worldwide. Different mechanisms are related to the pathogenesis of stroke, involving multiple biological systems, which are often inter-connected. Besides age, hypertension is the most important risk factor for stroke and may also predispose to the development of more subtle cerebral damage based on arteriolar narrowing or pathological microvascular changes. Age and high blood pressure are responsible for silent structural and functional cerebral changes leading to white matter lesions and cognitive impairment. The clinical significance and pathological substrate of white matter lesions are not fully understood. Hypertensive patients have more white matter lesions, which are an important prognostic factor for the development of stroke, cognitive impairment, dementia and death, than normotensive people. Over the past 10 years, strong evidence has emerged that cerebral white matter lesions in hypertensive patients should be considered a silent early marker of brain damage. The mechanisms that would explain all these relationships remain to be elucidated, but available data suggest that arteriosclerosis of the penetrating brain vessels is the main factor in the pathogenesis of ischemic white matter lesions.

  6. The Association between Cerebral White Matter Lesions and Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acids Ratio to Cognitive Impairment Development

    Directory of Open Access Journals (Sweden)

    Michihiro Suwa

    2015-01-01

    Full Text Available Objective. Cerebral white matter hyperintensity (WMH with magnetic resonance imaging (MRI has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment. Methods. Atherosclerotic risk factors, the internal carotid artery (ICA plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA and docosahexaenoic to arachidonic acids (DHA/AA were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE. Results. The development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (<0.38, obtained as the median value but was not related to dyslipidemia, diabetes, smoking, and a low serum DHA/AA ratio (<0.84, obtained as the median value. In addition, the MMSE score deteriorated slightly with the progression of WMH (29.7 ± 1.0 compared to 28.4 ± 2.1, P<0.0001. Conclusions. The progression of WMH was associated with a low serum EPA/AA ratio and accompanied minimal deterioration in cognitive function. Sufficient omega-3 PUFA intake may be effective in preventing the development of cognitive impairment.

  7. Peso de nascimento como preditor para a gravidade da lesão da substância branca cerebral neonatal Birth weight as predictor for the severity of neonatal brain white matter lesion

    Directory of Open Access Journals (Sweden)

    Nayara Argollo

    2006-06-01

    Full Text Available Para analisar a associação entre fatores natais com a gravidade da lesão da substância branca (LSB cerebral neonatal, controlando o peso de nascimento, identificaram os neonatos pela ultra-sonografia craniana, que foram divididos em: aqueles com evolução da LSC para resolução da imagem ao ultra-som (menor gravidade e, aqueles que evoluiram com formação de cistos e/ou ventriculomegalia e/ou hemorragia (maior gravidade. Doze variáveis (hiponatremia, anemia, infecção, retinopatia, displasia broncopulmonar, hipoalbuminemia, persistência do canal arterial, audiometria alterada, desconforto respiratório precoce, peso de nascimento To analyze the association of natal factors with the severity of neonatal brain white matter lesion (WML by controlling the birth weight, we identified newborns with WML who were divided into: those with WML evolution towards resolution of the ultrasound image (less severe, and those who evolved with cist formation and/or ventriculomegalia and/or hemorrhage (greater severity. There were differences among the twelve variables (hyponatremia, anemia, infection, retinopathy, broncopulmonary dysplasia, hypoalbuminemia, persistence of the arterial canal, altered audiometry, early respiratory distress, birth weigh below 2,500 g, weight per category, and prematurity between the two groups (p<0.05, being that nine variables (hyponatremia, infection, retinopathy, hypoalbuminemia, persistence of the arterial canal, early respiratory distress, low weight, prematurity, and weight per category remained statistically different (p<0.01 after the logistic regression analysis. When the variables were analyzed by birth weight category none of them presented statistical significance. This study suggests that birth weight is the major factor - likely the only one - associated to the severity of neonatal brain white matter lesion.

  8. Bootstrapping white matter segmentation, Eve++

    Science.gov (United States)

    Plassard, Andrew; Hinton, Kendra E.; Venkatraman, Vijay; Gonzalez, Christopher; Resnick, Susan M.; Landman, Bennett A.

    2015-03-01

    Multi-atlas labeling has come in wide spread use for whole brain labeling on magnetic resonance imaging. Recent challenges have shown that leading techniques are near (or at) human expert reproducibility for cortical gray matter labels. However, these approaches tend to treat white matter as essentially homogeneous (as white matter exhibits isointense signal on structural MRI). The state-of-the-art for white matter atlas is the single-subject Johns Hopkins Eve atlas. Numerous approaches have attempted to use tractography and/or orientation information to identify homologous white matter structures across subjects. Despite success with large tracts, these approaches have been plagued by difficulties in with subtle differences in course, low signal to noise, and complex structural relationships for smaller tracts. Here, we investigate use of atlas-based labeling to propagate the Eve atlas to unlabeled datasets. We evaluate single atlas labeling and multi-atlas labeling using synthetic atlases derived from the single manually labeled atlas. On 5 representative tracts for 10 subjects, we demonstrate that (1) single atlas labeling generally provides segmentations within 2mm mean surface distance, (2) morphologically constraining DTI labels within structural MRI white matter reduces variability, and (3) multi-atlas labeling did not improve accuracy. These efforts present a preliminary indication that single atlas labels with correction is reasonable, but caution should be applied. To purse multi-atlas labeling and more fully characterize overall performance, more labeled datasets would be necessary.

  9. Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain

    NARCIS (Netherlands)

    Farkas, E; Donka, G; de Vos, RAI; Mihaly, A; Bari, F; Luiten, PGM; Vos, Rob A.I. de

    Though cerebral white matter injury is a frequently described phenomenon in aging and dementia, the cause of white matter lesions has not been conclusively determined. Since the lesions are often associated with cerebrovascular risk factors, ischemia emerges as a potential condition for the

  10. Continuous subcortical motor evoked potential stimulation using the tip of an ultrasonic aspirator for the resection of motor eloquent lesions.

    Science.gov (United States)

    Shiban, Ehab; Krieg, Sandro M; Obermueller, Thomas; Wostrack, Maria; Meyer, Bernhard; Ringel, Florian

    2015-08-01

    Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs. An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator's use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location. The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14). Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a

  11. Automatic segmentation of white matter hyperintensities robust to multicentre acquisition and pathological variability

    Science.gov (United States)

    Samaille, T.; Colliot, O.; Cuingnet, R.; Jouvent, E.; Chabriat, H.; Dormont, D.; Chupin, M.

    2012-02-01

    White matter hyperintensities (WMH), commonly seen on FLAIR images in elderly people, are a risk factor for dementia onset and have been associated with motor and cognitive deficits. We present here a method to fully automatically segment WMH from T1 and FLAIR images. Iterative steps of non linear diffusion followed by watershed segmentation were applied on FLAIR images until convergence. Diffusivity function and associated contrast parameter were carefully designed to adapt to WMH segmentation. It resulted in piecewise constant images with enhanced contrast between lesions and surrounding tissues. Selection of WMH areas was based on two characteristics: 1) a threshold automatically computed for intensity selection, 2) main location of areas in white matter. False positive areas were finally removed based on their proximity with cerebrospinal fluid/grey matter interface. Evaluation was performed on 67 patients: 24 with amnestic mild cognitive impairment (MCI), from five different centres, and 43 with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoaraiosis (CADASIL) acquired in a single centre. Results showed excellent volume agreement with manual delineation (Pearson coefficient: r=0.97, p<0.001) and substantial spatial correspondence (Similarity Index: 72%+/-16%). Our method appeared robust to acquisition differences across the centres as well as to pathological variability.

  12. Different scaling of white matter volume, cortical connectivity, and gyrification across rodent and primate brains

    Science.gov (United States)

    Ventura-Antunes, Lissa; Mota, Bruno; Herculano-Houzel, Suzana

    2013-01-01

    Expansion of the cortical gray matter in evolution has been accompanied by an even faster expansion of the subcortical white matter volume and by folding of the gray matter surface, events traditionally considered to occur homogeneously across mammalian species. Here we investigate how white matter expansion and cortical folding scale across species of rodents and primates as the gray matter gains neurons. We find very different scaling rules of white matter expansion across the two orders, favoring volume conservation and smaller propagation times in primates. For a similar number of cortical neurons, primates have a smaller connectivity fraction and less white matter volume than rodents; moreover, as the cortex gains neurons, there is a much faster increase in white matter volume and in its ratio to gray matter volume in rodents than in primates. Order-specific scaling of the white matter can be attributed to different scaling of average fiber caliber and neuronal connectivity in rodents and primates. Finally, cortical folding increases as different functions of the number of cortical neurons in rodents and primates, scaling faster in the latter than in the former. While the neuronal rules that govern gray and white matter scaling are different across rodents and primates, we find that they can be explained by the same unifying model, with order-specific exponents. The different scaling of the white matter has implications for the scaling of propagation time and computational capacity in evolution, and calls for a reappraisal of developmental models of cortical expansion in evolution. PMID:23576961

  13. Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

    Directory of Open Access Journals (Sweden)

    Simona Fiori

    2015-01-01

    Conclusion: The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP.

  14. Utilization behavior as a white matter disconnection syndrome.

    Science.gov (United States)

    Ishihara, Kenji; Nishino, Hiroshi; Maki, Toshiyuki; Kawamura, Mitsuru; Murayama, Shigeo

    2002-06-01

    We report a case of utilization behavior that was examined neuropathologically. A 72-year-old right-handed male patient, who was admitted with a complaint of transient loss of consciousness, displayed utilization behavior several times. He used daily objects that were placed in front of him, such as a teacup and a toothbrush, without instructions to do so. If the examiner asked the patient not to use the objects, the patient did not use them. MRI revealed acute infarction of the left superior frontal gyrus, where decreased blood flow was revealed by SPECT. The patient died of an acute worsening of dilated cardiomyopathy. Neuropathological examination demonstrated an acute phase infarction of the subcortical white matter of the left superior frontal lobe, which correlated well with neuroradiological findings. Utilization behavior has been thought a "frontal lobe symptom". However, we propose that utilization behavior might be considered a white matter disconnection syndrome.

  15. Fusing Markov random fields with anatomical knowledge and shape-based analysis to segment multiple sclerosis white matter lesions in magnetic resonance images of the brain

    Science.gov (United States)

    AlZubi, Stephan; Toennies, Klaus D.; Bodammer, N.; Hinrichs, Herman

    2002-05-01

    This paper proposes an image analysis system to segment multiple sclerosis lesions of magnetic resonance (MR) brain volumes consisting of 3 mm thick slices using three channels (images showing T1-, T2- and PD -weighted contrast). The method uses the statistical model of Markov Random Fields (MRF) both at low and high levels. The neighborhood system used in this MRF is defined in three types: (1) Voxel to voxel: a low-level heterogeneous neighborhood system is used to restore noisy images. (2) Voxel to segment: a fuzzy atlas, which indicates the probability distribution of each tissue type in the brain, is registered elastically with the MRF. It is used by the MRF as a-priori knowledge to correct miss-classified voxels. (3) Segment to segment: Remaining lesion candidates are processed by a feature based classifier that looks at unary and neighborhood information to eliminate more false positives. An expert's manual segmentation was compared with the algorithm.

  16. White matter tracts critical for recognition of sarcasm.

    Science.gov (United States)

    Davis, Cameron L; Oishi, Kenichi; Faria, Andreia V; Hsu, John; Gomez, Yessenia; Mori, Susumu; Hillis, Argye E

    2016-01-01

    Failure to recognize sarcasm can lead to important miscommunications. Few previous studies have identified brain lesions associated with impaired recognition of sarcasm. We tested the hypothesis that percent damage to specific white matter tracts, age, and education together predict accuracy in sarcasm recognition. Using multivariable linear regression, with age, education, and percent damage to each of eight white matter tracts as independent variables, and percent accuracy on sarcasm recognition as the dependent variable, we developed a model for predicting sarcasm recognition. Percent damage to the sagittal stratum had the greatest weight and was the only independent predictor of sarcasm recognition.

  17. An advanced white matter tract analysis in frontotemporal dementia and early-onset Alzheimer's disease.

    Science.gov (United States)

    Daianu, Madelaine; Mendez, Mario F; Baboyan, Vatche G; Jin, Yan; Melrose, Rebecca J; Jimenez, Elvira E; Thompson, Paul M

    2016-12-01

    Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally

  18. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

    DEFF Research Database (Denmark)

    Fennema-Notestine, C; Archibald, S.L.; Jacobsen, M.W.

    2004-01-01

    OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age......, supporting a similar mechanism of degeneration...

  19. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease

    DEFF Research Database (Denmark)

    Fennema-Notestine, C; Archibald, S.L.; Jacobsen, M.W.

    2004-01-01

    OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age...

  20. [A case of progressive multifocal leukoencephalopathy presenting white matter MRI lesions extending over the cerebral cortex and a marked decrease in cerebral blood flow on SPECT, and associated with HTLV-I infection].

    Science.gov (United States)

    Takase, Kei-ichiro; Ohyagi, Yasumasa; Furuya, Hirokazu; Nagashima, Kazuo; Taniwaki, Takayuki; Kira, Jun-ichi

    2005-06-01

    We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein

  1. White matter microstructural organization and gait stability in older adults

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    Sjoerd M. Bruijn

    2014-06-01

    Full Text Available Understanding age-related decline in gait stability and the role of alterations in brain structure is crucial. Here, we studied the relationship between white matter microstructural organization using Diffusion Tensor Imaging (DTI and advanced gait stability measures in 15 healthy young adults (range 18-30 years and 25 healthy older adults (range 62-82 years.Among the different gait stability measures, only stride time and the maximum Lyapunov exponent (which quantifies how well participants are able to attenuate small perturbations were found to decline with age. White matter microstructural organization (FA was lower throughout the brain in older adults. We found a strong correlation between FA in the left anterior thalamic radiation and left corticospinal tract on the one hand, and step width and safety margin (indicative of how close participants are to falling over on the other. These findings suggest that white matter FA in tracts connecting subcortical and prefrontal areas is associated with the implementation of an effective stabilization strategy during gait.

  2. White matter microstructural organization and gait stability in older adults

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    Bruijn, Sjoerd M.; Van Impe, Annouchka; Duysens, Jacques; Swinnen, Stephan P.

    2014-01-01

    Understanding age-related decline in gait stability and the role of alterations in brain structure is crucial. Here, we studied the relationship between white matter microstructural organization using Diffusion Tensor Imaging (DTI) and advanced gait stability measures in 15 healthy young adults (range 18–30 years) and 25 healthy older adults (range 62–82 years). Among the different gait stability measures, only stride time and the maximum Lyapunov exponent (which quantifies how well participants are able to attenuate small perturbations) were found to decline with age. White matter microstructural organization (FA) was lower throughout the brain in older adults. We found a strong correlation between FA in the left anterior thalamic radiation and left corticospinal tract on the one hand, and step width and safety margin (indicative of how close participants are to falling over) on the other. These findings suggest that white matter FA in tracts connecting subcortical and prefrontal areas is associated with the implementation of an effective stabilization strategy during gait. PMID:24959139

  3. A clinical case of a patient with probable cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL from Chuvashia

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    Tatiana Vladimirovna Mokina

    2015-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL syndrome is a congenital small-vessel disease running with recurrent lacunar infarcts and leading to gradually progressive subcortical, pseudobulbar, and cerebellar syndromes and dementia. Neuroimaging reveal multiple lacunar infarcts in the basal ganglia, thalamus, pons Varolii, and cerebral hemispheric white matter, as well as cerebral atrophy. The specific feature of the disease is white matter lesion adjacent to the temporal horns of the lateral ventricles and to the external capsules. The paper describes a patient with CADASIL syndrome. The latter runs a progressive course and includes the following neurological disorders: cognitive, pyramidal, extrapyramidal, and axial ones. This clinical case was differentially diagnosed with multiple sclerosis, including with consideration for neuroimaging findings. The CADASIL syndrome is a rare potentially menacing neurological condition that is observed in young patients and requires a detailed examination using current diagnostic techniques.

  4. MR imaging of ischemic parenchymal lesions in moyamoya disease of children

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    Lee, Whal; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo; Han, Man Chung [Seoul National Univ. College of Medicine, the Institute of Radiation Medicine and Neuroscience Research Institute, SNUMRC, Seoul (Korea, Republic of); Cho, Byung Kyu; Wang, Kyu Chang; Hwang, Yong Seung [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-12-01

    To determine by means of MR imaging the ischemic status of parenchymal lesions in moyamoya disease. Ninety-two MR images in 50 children wiht moyamoya disease were retrospectively reviewed. Ischemic parenchymal lesions were categorized according to the signal intensities of cortex and subcortical white matter. We also analyzed enhancement patterns, time sequential changes in the lesions, and the Prognosis for each patient, according to lesion type. Among one hundred and seventeen parenchymal abnormalities, 89 gyral lesions were seen in 43 children (86%), predominantly in the frontal area (33.1%). Cortical parenchymal lesions were categorized as either type I-intermediate to high signal intensity (SI) on both T2 weighted (T2WI) and proton density images (PDI), and associated with low SI of the subcortical white matter;type II-high SI on T2WI and PDI, without low SI of the subcortical white matter;or type III-high SI on T2WI and iso SI on PDI. Thirty-three lesions were type I, ten were type II, and 43 were type III. Time sequential changes from type I to type II, and then to type III, were observed. The prognoses of patients with a type-I lesion were better than those of patients whose lesions were type II or III. Type I lesions presented with abnormal low signal intensity in the subcortical white matter, as seen on T2WI Images. This was the characteristic and earliest finding of ischemic parenchymal lesions in moyamoya disease; sequential MR images showed that type-I lesions progressed to type II or III.

  5. Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke.

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    Griffis, Joseph C; Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

    2017-01-01

    Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

  6. Brain white matter lesions correlated to newborns death and lethality Fatores correlacionados ao óbito e à letalidade hospitalar em neonatos com lesão da substância branca cerebral

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    Nayara Argollo

    2006-06-01

    Full Text Available OBJECTIVES: to describe hospital lethality rates and factors correlated to death in neonates with brain white matter lesions. METHODS: a retrospective study was performed from January 1994 to December 2001. Neonates with white brain matter lesions were divided into survival and death groups and their medical files reviewed through the single blind method to determine evolution. Death certificates provided the cause of death. The groups were compared through correlation coefficients. Hospital lethality rate was calculated. RESULTS: ninety three cases of white brain matter lesions and seven deaths were determined. Hospital lethality rate was of 8.2.% (95%CI: 2.4-14.0 independently from lesion occurrence time, and of 10.3% (95%CI: 3.3-17.3 for deaths occurred during prenatal and perinatal periods. Death was correlated to: Apgar score, non-cephalic presentation, gestational age, hyperglicemia, hypercalcemia, convulsion, respiratory insufficiency and atelectasy. CONCLUSIONS: hospital lethality was of 10.3% generating the following hypothesis: perinatal asphyxia must be the principal direct and indirect etiologic factor (aggravating the expression of prematurity and infection diseases, of prenatal and perinatal mortality among newborns with white brain matter lesions; and OBJETIVOS: descrever a taxa de letalidade hospitalar e fatores correlacionados com o óbito em crianças com lesão da substância branca cerebral (LSB. MÉTODOS: estudo retrospectivo realizado de janeiro de 1994 a dezembro de 2001. Os neonatos com LSB foram divididos em sobreviventes ou óbito, e seus prontuários revisados de forma cega para a evolução. Dos atestados de óbito, a causa de morte. Os grupos foram comparados por coeficientes de correlação. Calculada a taxa de letalidade hospitalar. RESULTADOS: foram encontrados 93 casos de LSB e sete óbitos. A taxa de letalidade hospitalar foi de 8,2%, (IC95%: 2,4-14,0, independentemente da época de instalação da lesão, e de

  7. Traumatic white matter injury and toxic leukoencephalopathies.

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    Al-Hasani, Omer Hussain; Smith, Colin

    2011-09-01

    White matter injury may be secondary to a range of neurodegenerative disorders, such as the common dementing disorders of the elderly, or may be a consequence of specific white matter disorders, such as multiple sclerosis and the rare leukodystrophies. This article will focus on two relatively common primary groups of disorders of the white matter, traumatic white matter injury and toxic leukoencephalopathies. Traumatic axonal injury may be focal or diffuse, and is associated with a clinical spectrum ranging from concussion through to coma and death. The molecular mechanisms underlying axonal degeneration secondary to traumatic axonal degeneration are being elucidated and may give an insight into potential therapeutic targets. Toxic leukoencephalopathy may be secondary to exposure to a wide range of compounds, including chemotherapeutic drugs. These toxins may produce white matter injury through a range of mechanisms, and the potential toxic effects of compounds need to be considered when assessing a patient with a nonspecific leukoencephalopathy.

  8. White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs.

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    Klauser, Paul; Baker, Simon T; Cropley, Vanessa L; Bousman, Chad; Fornito, Alex; Cocchi, Luca; Fullerton, Janice M; Rasser, Paul; Schall, Ulrich; Henskens, Frans; Michie, Patricia T; Loughland, Carmel; Catts, Stanley V; Mowry, Bryan; Weickert, Thomas W; Shannon Weickert, Cynthia; Carr, Vaughan; Lenroot, Rhoshel; Pantelis, Christos; Zalesky, Andrew

    2017-03-01

    White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain's fiber bundles. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Genetics Home Reference: leukoencephalopathy with vanishing white matter

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    ... Leukoencephalopathy with vanishing white matter Leukoencephalopathy with vanishing white matter Printable PDF Open All Close All Enable ... the expand/collapse boxes. Description Leukoencephalopathy with vanishing white matter is a progressive disorder that mainly affects ...

  10. Exploring the multiple-hit hypothesis of preterm white matter damage using diffusion MRI.

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    Barnett, Madeleine L; Tusor, Nora; Ball, Gareth; Chew, Andrew; Falconer, Shona; Aljabar, Paul; Kimpton, Jessica A; Kennea, Nigel; Rutherford, Mary; David Edwards, A; Counsell, Serena J

    2018-01-01

    Preterm infants are at high risk of diffuse white matter injury and adverse neurodevelopmental outcome. The multiple hit hypothesis suggests that the risk of white matter injury increases with cumulative exposure to multiple perinatal risk factors. Our aim was to test this hypothesis in a large cohort of preterm infants using diffusion weighted magnetic resonance imaging (dMRI). We studied 491 infants (52% male) without focal destructive brain lesions born at hypothesis that increased exposure to perinatal risk factors was associated with lower fractional anisotropy (FA), and higher radial, axial and mean diffusivity (RD, AD, MD) in white matter. Neurodevelopmental performance was investigated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III) in a subset of 381 infants at 20 months corrected age. We tested the hypothesis that lower FA and higher RD, AD and MD in white matter were associated with poorer neurodevelopmental performance. Identified risk factors for diffuse white matter injury were lower GA at birth, fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition, necrotizing enterocolitis and male sex. Clinical chorioamnionitis and patent ductus arteriosus were not associated with white matter injury. Multivariate analysis demonstrated that fetal growth restriction, increased number of days requiring ventilation and parenteral nutrition were independently associated with lower FA values. Exposure to cumulative risk factors was associated with reduced white matter FA and FA values at term equivalent age were associated with subsequent neurodevelopmental performance. This study suggests multiple perinatal risk factors have an independent association with diffuse white matter injury at term equivalent age and exposure to multiple perinatal risk factors exacerbates dMRI defined, clinically significant white matter injury. Our findings support the multiple hit hypothesis for preterm white

  11. White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders.

    Science.gov (United States)

    Longoni, Giulia; Brown, Robert A; MomayyezSiahkal, Parya; Elliott, Colm; Narayanan, Sridar; Bar-Or, Amit; Marrie, Ruth Ann; Yeh, E Ann; Filippi, Massimo; Banwell, Brenda; Arnold, Douglas L

    2017-05-01

    See Hacohen et al. (doi:10.1093/awx075) for a scientific commentary on this article. Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal

  12. Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts.

    Science.gov (United States)

    Berthier, Marcelo L; De-Torres, Irene; Paredes-Pacheco, José; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María J; Alfaro, Francisco; Moreno-Torres, Ignacio; López-Barroso, Diana; Dávila, Guadalupe

    2017-01-01

    Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI), and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In

  13. The hidden-Markov brain: comparison and inference of white matter hyperintensities on magnetic resonance imaging (MRI)

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    Pham, Tuan D.; Salvetti, Federica; Wang, Bing; Diani, Marco; Heindel, Walter; Knecht, Stefan; Wersching, Heike; Baune, Bernhard T.; Berger, Klaus

    2011-02-01

    Rating and quantification of cerebral white matter hyperintensities on magnetic resonance imaging (MRI) are important tasks in various clinical and scientific settings. As manual evaluation is time consuming and imprecise, much effort has been made to automate the quantification of white matter hyperintensities. There is rarely any report that attempts to study the similarity/dissimilarity of white matter hyperintensity patterns that have different sizes, shapes and spatial localizations on the MRI. This paper proposes an original computational neuroscience framework for such a conceptual study with a standpoint that the prior knowledge about white matter hyperintensities can be accumulated and utilized to enable a reliable inference of the rating of a new white matter hyperintensity observation. This computational approach for rating inference of white matter hyperintensities, which appears to be the first study, can be utilized as a computerized rating-assisting tool and can be very economical for diagnostic evaluation of brain tissue lesions.

  14. Neurotransmitter signaling in white matter.

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    Butt, Arthur M; Fern, Robert F; Matute, Carlos

    2014-11-01

    White matter (WM) tracts are bundles of myelinated axons that provide for rapid communication throughout the CNS and integration in grey matter (GM). The main cells in myelinated tracts are oligodendrocytes and astrocytes, with small populations of microglia and oligodendrocyte precursor cells. The prominence of neurotransmitter signaling in WM, which largely exclude neuronal cell bodies, indicates it must have physiological functions other than neuron-to-neuron communication. A surprising aspect is the diversity of neurotransmitter signaling in WM, with evidence for glutamatergic, purinergic (ATP and adenosine), GABAergic, glycinergic, adrenergic, cholinergic, dopaminergic and serotonergic signaling, acting via a wide range of ionotropic and metabotropic receptors. Both axons and glia are potential sources of neurotransmitters and may express the respective receptors. The physiological functions of neurotransmitter signaling in WM are subject to debate, but glutamate and ATP-mediated signaling have been shown to evoke Ca(2+) signals in glia and modulate axonal conduction. Experimental findings support a model of neurotransmitters being released from axons during action potential propagation acting on glial receptors to regulate the homeostatic functions of astrocytes and myelination by oligodendrocytes. Astrocytes also release neurotransmitters, which act on axonal receptors to strengthen action potential propagation, maintaining signaling along potentially long axon tracts. The co-existence of multiple neurotransmitters in WM tracts suggests they may have diverse functions that are important for information processing. Furthermore, the neurotransmitter signaling phenomena described in WM most likely apply to myelinated axons of the cerebral cortex and GM areas, where they are doubtless important for higher cognitive function. © 2014 Wiley Periodicals, Inc.

  15. Impairment of visuospatial/visuoconstructional skills in multiple sclerosis patients: the correlation with regional lesion load and subcortical atrophy.

    Science.gov (United States)

    Marasescu, R; Cerezo Garcia, M; Aladro Benito, Y

    2016-04-01

    About 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS-VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. To evaluate the relationship between VS-VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. Of 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS-VC impairments in the following tests: Incomplete picture, Block design (WAIS-III), and Rey-Osterrieth complex figure test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of school) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (Block design: P=.001; Rey-Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (Block design: P=.000; Rey-Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (Incomplete picture; P=.002). Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks. Copyright © 2015

  16. An unusual case of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with occipital lobe involvement

    Directory of Open Access Journals (Sweden)

    Bhavesh Trikamji

    2016-01-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an autosomal dominant angiopathy caused by a mutation in the notch 3 gene on chromosome 19. Clinically, patients may be asymptomatic or can present with recurrent ischemic episodes and strokes leading to dementia, depression, pseudobulbar palsy, and hemi- or quadraplegia. Additional manifestations that have been described include migraine (mostly with aura, psychiatric disturbances, and epileptic seizures. Neuroimaging is essential to the diagnosis of CADASIL. On imaging CADASIL is characterized by symmetric involvement by confluent lesions located subcortically in the frontal and temporal lobes as well as in the insula, periventricularly, in the centrum semiovale, in the internal and external capsule, basal ganglia, and brain stem; with relative sparing of the fronto-orbital and the occipital subcortical regions. We describe a 49 year old male with CADASIL with absence of temporal lobe findings on MRI but predominant lesions within the periventricular white matter, occipital lobes with extension into the subcortical frontal lobes, corpus callosum and cerebellar white matter. Although CADASIL characteristically presents with anterior temporal lobe involvement, these findings may be absent and our case addresses the atypical imaging findings in CADASIL.

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

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

    2012-10-15

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

  18. White Matter Integrity Deficit Associated with Betel Quid Dependence

    Directory of Open Access Journals (Sweden)

    Fulai Yuan

    2017-10-01

    Full Text Available Betel quid (BQ is a commonly consumed psychoactive substance, which has been regarded as a human carcinogen. Long-term BQ chewing may cause Diagnostic and Statistical Manual of Mental Disorders-IV dependence symptoms, which can lead to decreased cognitive functions, such as attention and inhibition control. Although betel quid dependence (BQD individuals have been reported with altered brain structure and function, there is little evidence showing white matter microstructure alternation in BQD individuals. The present study aimed to investigate altered white matter microstructure in BQD individuals using diffusion tensor imaging. Tract-based spatial statistics was used to analyze the data. Compared with healthy controls, BQD individuals exhibited higher mean diffusivity (MD in anterior thalamic radiation (ATR. Further analysis revealed that the ATR in BQD individuals showed less fractional anisotropy (FA than that in healthy controls. Correlation analysis showed that both the increase of MD and reduction of FA in BQD individuals were associated with severity of BQ dependence. These results suggested that BQD would disrupt the balance between prefrontal cortex and subcortical areas, causing declined inhibition control.

  19. The white matter query language: a novel approach for describing human white matter anatomy.

    Science.gov (United States)

    Wassermann, Demian; Makris, Nikos; Rathi, Yogesh; Shenton, Martha; Kikinis, Ron; Kubicki, Marek; Westin, Carl-Fredrik

    2016-12-01

    We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist's expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.

  20. Age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI.

    Science.gov (United States)

    Henry Feugeas, Marie Cécile; De Marco, Giovanni; Peretti, Ilana Idy; Godon-Hardy, Sylvie; Fredy, Daniel; Claeys, Elisabeth Schouman

    2005-11-01

    Our purpose was to investigate leukoaraïosis (LA) using three-dimensional MR imaging combined with advanced image-processing technology to attempt to group signal abnormalities according to their etiology. Coronal T2-weighted fast fluid-attenuated inversion-recovery (FLAIR) sequences and three-dimensional T1-weighted fast spoiled gradient recalled echo sequences were used to examine cerebral white matter changes in 75 elderly people with memory complaint but no dementia. They were otherwise healthy, community-dwelling subjects. Three subtypes of LA were defined on the basis of their shape, geography and extent: the so-called subependymal/subpial LA, perivascular LA and "bands" along long white matter tracts. Subependymal changes were directly contiguous with ventricular spaces. They showed features of "water hammer" lesions with ventricular systematisation and a more frequent location around the frontal horns than around the bodies (P=.0008). The use of cerebrospinal fluid (CSF) contiguity criterion allowed a classification of splenial changes in the subpial group. Conversely, posterior periventricular lesions in the centrum ovale as well as irregular and extensive periventricular lesions were not directly contiguous with CSF spaces. The so-called perivascular changes showed features of small-vessel-associated disease; they surrounded linear CSF-like signals that followed the direction of perforating vessels. Distribution of these perivascular changes appeared heterogeneous (P ranging from .04 to 5.10(-16)). These findings suggest that subependymal/subpial LA and subcortical LA may be separate manifestations of a single underlying pulse-wave encephalopathy.

  1. In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

    Science.gov (United States)

    Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

    2017-11-01

    Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor

  2. The generation and validation of white matter connectivity importance maps.

    Science.gov (United States)

    Kuceyeski, Amy; Maruta, Jun; Niogi, Sumit N; Ghajar, Jamshid; Raj, Ashish

    2011-09-01

    Both the size and location of injury in the brain influences the type and severity of cognitive or sensorimotor dysfunction. However, even with advances in MR imaging and analysis, the correspondence between lesion location and clinical deficit remains poorly understood. Here, structural and diffusion images from 14 healthy subjects are used to create spatially unbiased white matter connectivity importance maps that quantify the amount of disruption to the overall brain network that would be incurred if that region were compromised. Some regions in the white matter that were identified as highly important by such maps have been implicated in strategic infarct dementia and linked to various attention tasks in previous studies. Validation of the maps is performed by investigating the correlations of the importance maps' predicted cognitive deficits in a group of 15 traumatic brain injury patients with their cognitive test scores measuring attention and memory. While no correlation was found between amount of white matter injury and cognitive test scores, significant correlations (r>0.68, pimprove surgical planning, diagnosis, and assessment of disease severity in a variety of pathologies like multiple sclerosis, trauma, and stroke. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Spaceflight Effect on White Matter Structural Integrity

    Science.gov (United States)

    Lee, Jessica K.; Kopplemans, Vincent; Paternack, Ofer; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2017-01-01

    Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

  4. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    Science.gov (United States)

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  5. White matter injury detection in neonatal MRI

    Science.gov (United States)

    Cheng, Irene; Hajari, Nasim; Firouzmanesh, Amirhossein; Shen, Rui; Miller, Steven; Poskitt, Ken; Basu, Anup

    2013-02-01

    Early detection of white matter injury in premature newborns can facilitate timely clinical treatments reducing the potential risk of later developmental deficits. It was reported that there were more than 5% premature newborns in British Columbia, Canada, among which 5-10% exhibited major motor deficits and 25-50% exhibited significant developmental and visual deficits. With the advancement of computer assisted detection systems, it is possible to automatically identify white matter injuries, which are found inside the grey matter region of the brain. Atlas registration has been suggested in the literature to distinguish grey matter from the soft tissues inside the skull. However, our subjects are premature newborns delivered at 24 to 32 weeks of gestation. During this period, the grey matter undergoes rapid changes and differs significantly from one to another. Besides, not all detected white spots represent injuries. Additional neighborhood information and expert input are required for verification. In this paper, we propose a white matter feature identification system for premature newborns, which is composed of several steps: (1) Candidate white matter segmentation; (2) Feature extraction from candidates; (3) Validation with data obtained at a later stage on the children; and (4) Feature confirmation for automated detection. The main challenge of this work lies in segmenting white matter injuries from noisy and low resolution data. Our approach integrates image fusion and contrast enhancement together with a fuzzy segmentation technique to achieve promising results. Other applications, such as brain tumor and intra-ventricular haemorrhage detection can also benefit from our approach.

  6. Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection.

    Science.gov (United States)

    Zeis, Thomas; Graumann, Ursula; Reynolds, Richard; Schaeren-Wiemers, Nicole

    2008-01-01

    Multiple sclerosis is a chronic inflammatory disease of the CNS. Although progressive axonal injury and diffuse inflammatory damage has been shown in the chronic phase of the disease, little is known about the molecular mechanisms underlying these pathological processes. In order to identify these mechanisms, we have studied the gene expression profile in non-lesion containing tissue, the so-called normal-appearing white matter (NAWM). We performed differential gene expression analysis and quantitative RT-PCR on subcortical white matter from 11 multiple sclerosis and 8 control cases. Differentially expressed genes were further analysed in detail by in situ hybridization and immunofluorescence studies. We show that genes known to be involved in anti-inflammatory and protective mechanisms such as STAT6, JAK1, IL-4R, IL-10, Chromogranin C and Hif-1alpha are consistently upregulated in the multiple sclerosis NAWM. On the other hand, genes involved in pro-inflammatory mechanisms, such as STAT4, IL-1beta and MCSF, were also upregulated but less regularly. Immunofluorescence colocalization analysis revealed expression of STAT6, JAK1, IL-4R and IL-13R mainly in oligodendrocytes, whereas STAT4 expression was detected predominantly in microglia. In line with these data, in situ hybridization analysis showed an increased expression in multiple sclerosis NAWM of HIF-1alpha in oligodendrocytes and HLA-DRalpha in microglia cells. The consistency of the expression levels of STAT6, JAK1, JAK3 and IL-4R between the multiple sclerosis cases suggests an overall activation of the STAT6-signalling pathway in oligodendrocytes, whereas the expression of STAT4 and HLA-DRalpha indicates the activation of pro-inflammatory pathways in microglia. The upregulation of genes involved in anti-inflammatory mechanisms driven by oligodendrocytes may protect the CNS environment and thus limit lesion formation, whereas the activation of pro-inflammatory mechanisms in microglia may favour disease

  7. The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease.

    Science.gov (United States)

    Minnerop, Martina; Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

    2011-12-01

    Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T(1)/T(2)/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (P(corrected) brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1

  8. White matter tract signatures of the progressive aphasias

    Science.gov (United States)

    Mahoney, Colin J.; Malone, Ian B.; Ridgway, Gerard R.; Buckley, Aisling H.; Downey, Laura E.; Golden, Hannah L.; Ryan, Natalie S.; Ourselin, Sebastien; Schott, Jonathan M.; Rossor, Martin N.; Fox, Nick C.; Warren, Jason D.

    2013-01-01

    The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity. PMID:23312804

  9. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Energy Technology Data Exchange (ETDEWEB)

    Wisnowski, Jessica L. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Ceschin, Rafael C. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Pittsburgh, Department of Biomedical Informatics, Pittsburgh, PA (United States); Choi, So Young [University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Schmithorst, Vincent J. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Painter, Michael J. [University of Pittsburgh, Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Blueml, Stefan [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States)

    2015-05-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  10. Intraoperative direct subcortical stimulation for identification of the internal capsule, combined with an image-guided stereotactic system during surgery for basal ganglia lesions.

    Science.gov (United States)

    Duffau, H

    2000-03-01

    The two main problems of surgery for basal ganglia lesions are: first, the difficulty of accurately localizing the lesion in this deep location; and second, the proximity to the internal capsule, with the risk of permanent postoperative sequelae. The author describes the use of intraoperative direct electrical subcortical stimulation in the identification and preservation of the internal capsule, combined with an image-guided stereotactic system for the selection of the best surgical approach in a case of deep cavernoma. A 33-year-old man was admitted to our institution with a history of three episodes of transitory left hemiparesia in the last 12 years. Neurological examination revealed a mild left weakness. Magnetic resonance imaging (MRI) showed typical features of a right posterior capsular-lentiform cavernoma. To prevent another hemorrhagic event, surgery was performed via a right transdistal sylvian approach, using a computer-assisted stereotactic method that allowed us to reach the lesion directly and direct stimulations to detect the subcortical pyramidal pathways. The patient had a transitory worsening with complete recovery in 10 days. Control MRI showed total resection. As described at the cortical level, the intraoperative direct subcortical stimulations seem also to represent an easy, safe, accurate, and reliable method of real-time functional identification of the internal capsule during surgery for basal ganglia lesions. The combination with an image-guided stereotactic system to accurately localize the lesion minimizes the risk of postoperative sequelae, and seems to warrant an increase of the surgical indications in this location.

  11. Linking white matter and deep gray matter alterations in premanifest Huntington disease.

    Science.gov (United States)

    Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J; Lee, David Soobin; van den Noort, Frieda; Wu, Dan; Brown, Timothy; Johnson, Hans; Paulsen, Jane S; Ross, Christopher A; Younes, Laurent; Miller, Michael I

    2016-01-01

    Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay

  12. Linking white matter and deep gray matter alterations in premanifest Huntington disease

    Directory of Open Access Journals (Sweden)

    Andreia V. Faria

    2016-01-01

    Full Text Available Huntington disease (HD is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i regions of interest surrounding these structures, using (ii tractography-based analysis, and using (iii whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores, and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be

  13. White matter cysts in patients with tuberous sclerosis; Quistes de sustancia blanca en pacientes con esclerosis tuberosa

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, L.; Dosda, R. [Hospital Universitario Dr. Peset. Servicio de Resonancia Magnetica ATQ-Quiron. Valencia (Spain); Menor, F. [Hospital Infantil La Fe. Valencia (Spain); Arana, E. [Hospital Casa de La Salud. Valencia (Spain); Poyatos, C. [Hospital Universitario Dr. Peset. Valencia (Spain)

    1999-07-01

    The presence of cysts in the white matter of the central nervous system of patients with tuberous sclerosis (TS) is an uncommon finding that has been reported only recently in neuroimaging studies. This article assesses the prevalence of these lesions in a large series of patients studied by magnetic resonance imaging (MRI) and their relationship to other epidemiological and imaging findings. MRI studies were performed in 46 patients (23 males and 23 females) with a mean age of 12.7 years, and the results were examined retrospectively in the search for cortical tubers, subependymal nodules and white matter nodules, lines and cysts. Nine patients (19.6%) presented cysts in white matter. Seven had only one cyst and the remaining two patients each had two. Multiple regression analysis relating the presence of the cysts with other neuroimaging findings in these patients revealed a statistically significant relationship only with white matter nodules (odds ratio: 7.5; p=0.006). White matter cysts are small, supratentorial lesions of deep location. There is a statistically relationship between the presence of these cysts and that of nodular lesions in the white matter. This finding supports the theory that the cyst originate from white matter nodules. (Author) 17 refs.

  14. Canavan Disease: A White Matter Disorder

    Science.gov (United States)

    Kumar, Shalini; Mattan, Natalia S.; de Vellis, Jean

    2006-01-01

    Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life.…

  15. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes.

    Science.gov (United States)

    Hollocks, Matthew J; Lawrence, Andrew J; Brookes, Rebecca L; Barrick, Thomas R; Morris, Robin G; Husain, Masud; Markus, Hugh S

    2015-12-01

    Small vessel disease is a stroke subtype characterized by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. Participants with small vessel disease (n = 118; mean age = 68.9 years; 65% male) defined as a clinical and magnetic resonance imaging confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. Healthy controls (n = 398; mean age = 64.3 years; 52% male) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify: (i) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment; and (ii) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole-brain voxel-based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = -0.23, P ≤ 0.001) and depression (r = -0.41, P ≤ 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = -0.38, P

  16. White Matter Structure in Older Adults Moderates the Benefit of Sleep Spindles on Motor Memory Consolidation.

    Science.gov (United States)

    Mander, Bryce A; Zhu, Alyssa H; Lindquist, John R; Villeneuve, Sylvia; Rao, Vikram; Lu, Brandon; Saletin, Jared M; Ancoli-Israel, Sonia; Jagust, William J; Walker, Matthew P

    2017-11-29

    Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits.SIGNIFICANCE STATEMENT Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of

  17. Protective effects of carnosine on white matter damage induced by chronic cerebral hypoperfusion

    Directory of Open Access Journals (Sweden)

    Jing Ma

    2016-01-01

    Full Text Available Carnosine is a dipeptide that scavenges free radicals, inhibits inflammation in the central nervous system, and protects against ischemic and hypoxic brain damage through its anti-oxidative and anti-apoptotic actions. Therefore, we hypothesized that carnosine would also protect against white matter damage caused by subcortical ischemic injury. White matter damage was induced by right unilateral common carotid artery occlusion in mice. The animals were treated with 200, 500 or 750 mg/kg carnosine by intraperitoneal injection 30 minutes before injury and every other day after injury. Then, 37 days later, Klüver-Barrera staining, toluidine blue staining and immunofluorescence staining were performed. Carnosine (200, 500 mg/kg substantially reduced damage to the white matter in the corpus callosum, internal capsule and optic tract, and it rescued expression of myelin basic protein, and alleviated the loss of oligodendrocytes. However, carnosine at the higher dose of 750 mg/kg did not have the same effects as the 200 and 500 mg/kg doses. These findings show that carnosine, at a particular dose range, protects against white matter damage caused by chronic cerebral ischemia in mice, likely by reducing oligodendroglial cell loss.

  18. Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

    Science.gov (United States)

    Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

    2015-01-01

    Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

  19. Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people.

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

    Full Text Available BACKGROUND: White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH. Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT Val158Met polymorphism in healthy populations remains unclear. METHODS: We recruited 315 ethnic Chinese adults with a mean age of 54.9 ± 21.8 years (range: 21-89 y to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant. RESULTS: Negative correlations between the Digit Span Forward (DSF score and frontal WMH volumes (r = -.123, P = .032, uncorrected were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (P = .016, uncorrected, whole brain (P = .047, uncorrected, and a trend over the frontal region (P = .050, uncorrected were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen's f revealed a small effect. CONCLUSIONS: The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.

  20. White Matter Glial Pathology in Autism

    Science.gov (United States)

    2015-11-01

    AWARD NUMBER: W81XWH-12-1-0302 TITLE: White Matter Glial Pathology in Autism PRINCIPAL INVESTIGATOR: Gregory A. Ordway, Ph.D. CONTRACTING... Pathology in Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0302 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gregory A. Ordway, Ph.D...imaging in living patients and pathology studies using postmortem brain tissues from deceased autism spectrum disorder (ASD) donors. These methods

  1. Quantifying the effects of normal ageing on white matter structure using unsupervised tract shape modelling.

    Science.gov (United States)

    Bastin, Mark E; Muñoz Maniega, Susana; Ferguson, Karen J; Brown, Laura J; Wardlaw, Joanna M; MacLullich, Alasdair M J; Clayden, Jonathan D

    2010-05-15

    Quantitative tractography may provide insights into regional heterogeneity of changes in white matter structure in normal ageing. Here we examine how brain atrophy and white matter lesions affect correlations between tract shape, tract integrity and age in a range of frontal and non-frontal tracts in 90 non-demented subjects aged over 65 years using an enhanced version of probabilistic neighbourhood tractography. This novel method for automatic single seed point placement employs unsupervised learning and streamline selection to provide reliable and accurate tract segmentation, whilst also indicating how the shape of an individual tract compares to that of a predefined reference tract. There were significant negative correlations between tract shape similarity to reference tracts derived from a young brain white matter atlas and age in genu and splenium of corpus callosum. Controlling for intracranial and lateral ventricle volume, the latter of which increased significantly with age, attenuated these correlations by 40% and 84%, respectively, indicating that this age-related change in callosal tract topology is significantly mediated by global atrophy and ventricular enlargement. In accordance with the "frontal ageing" hypothesis, there was a significant positive correlation between mean diffusivity (D) and age, and a significant negative correlation between fractional anisotropy (FA) and age in corpus callosum genu; correlations not seen in splenium. Significant positive correlations were also observed between D and age in bilateral cingulum cingulate gyri, uncinate fasciculi and right corticospinal tract. This pattern of correlations was not, however, reproduced when those subjects with significant white matter lesion load were analyzed separately from those without. These data therefore suggest that brain atrophy and white matter lesions play a significant role in driving regional patterns of age-related changes in white matter tract shape and integrity

  2. Financial literacy is associated with white matter integrity in old age.

    Science.gov (United States)

    Han, S Duke; Boyle, Patricia A; Arfanakis, Konstantinos; Fleischman, Debra; Yu, Lei; James, Bryan D; Bennett, David A

    2016-04-15

    Financial literacy, the ability to understand, access, and utilize information in ways that contribute to optimal financial outcomes, is important for independence and wellbeing in old age. We previously reported that financial literacy is associated with greater functional connectivity between brain regions in old age. Here, we tested the hypothesis that higher financial literacy would be associated with greater white matter integrity in old age. Participants included 346 persons without dementia (mean age=81.36, mean education=15.39, male/female=79/267, mean MMSE=28.52) from the Rush Memory and Aging Project. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. White matter integrity was assessed with diffusion anisotropy measured with diffusion tensor magnetic resonance imaging (DTI). We tested the hypothesis that higher financial literacy is associated with higher diffusion anisotropy in white matter, adjusting for the effects of age, education, sex, and white matter hyperintense lesions. We then repeated the analysis also adjusting for cognitive function. Analyses revealed regions with significant positive associations between financial literacy and diffusion anisotropy, and many remained significant after accounting for cognitive function. White matter tracts connecting right hemisphere temporal-parietal brain regions were particularly implicated. Greater financial literacy is associated with higher diffusion anisotropy in white matter of nondemented older adults after adjusting for important covariates. These results suggest that financial literacy is positively associated with white matter integrity in old age. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Reduced white matter integrity in amateur boxers.

    Science.gov (United States)

    Herweh, Christian; Hess, Klaus; Meyding-Lamadé, Uta; Bartsch, Andreas J; Stippich, Christoph; Jost, Joachim; Friedmann-Bette, Birgit; Heiland, Sabine; Bendszus, Martin; Hähnel, Stefan

    2016-09-01

    Professional boxing can lead to chronic traumatic encephalopathy, a variant of traumatic brain injury (TBI). Its occurrence in amateur boxers is a matter of debate since amateur boxing is considered to be less harmful due to more strict regulations. However, several studies using different methodological approaches have revealed subtle signs of TBI even in amateurs. Diffusion tensor imaging (DTI) is sensitive to microscopic white matter changes and has been proven useful in TBI when routine MR imaging often is unrevealing. DTI, with tract-based spatial statistics (TBSS) together with neuropsychological examination of executive functions and memory, was used to investigate a collective of 31 male amateur boxers and 31 age-matched controls as well as a subgroup of 19 individuals, respectively, who were additionally matched for intellectual performance (IQ). All participants had normal findings in neurological examination and conventional MR. Amateur boxers did not show deficits in neuropsychological tests when their IQ was taken into account. Fractional anisotropy was significantly reduced, while diffusivity measures were increased along central white matter tracts in the boxers group. These changes were in part associated with the number of fights. TBSS revealed widespread white matter disturbance partially related to the individual fighting history in amateur boxers. These findings closely resemble those in patients with accidental TBI and indicate similar histological changes in amateur boxers.

  4. Focal cortical dysplasia type IIb: completeness of cortical, not subcortical, resection is necessary for seizure freedom.

    Science.gov (United States)

    Wagner, Jan; Urbach, Horst; Niehusmann, Pitt; von Lehe, Marec; Elger, Christian E; Wellmer, Jörg

    2011-08-01

    Focal cortical dysplasia type IIb (FCD IIb) lesions are highly epileptogenic and frequently cause pharmacoresistant epilepsy. Complete surgical resection leads to seizure freedom in most cases. However, the term "complete" resection is controversial with regard to the necessity of performing resections of the subcortical zone, which is frequently seen in these lesions on magnetic resonance imaging (MRI). We retrospectively analyzed 50 epilepsy patients with histologically proven FCD IIb. The extent of surgical resection was determined by SPM5-based coregistration of the preoperative and postoperative MRI scans. Postoperative outcome was analyzed with regard to (1) the completeness of the resection of the cortical abnormality and (2) the completeness of the resection of the subcortical abnormality. Complete resection of the cortical abnormality led to postoperative seizure freedom (Engel class Ia) in 34 of 37 patients (92%), whereas incomplete cortical resection achieved this in only one of 13 patients (8%, p < 0.001). Among the patients with complete cortical resection, 36 had FCDs with a subcortical hyperintensity according to MRI. In this group, complete resection of the subcortical abnormality did not result in a better postoperative outcome than incomplete resection (90% vs. 93% for Engel class Ia, n.s.). Complete resection of the MRI-documented cortical abnormality in FCD IIb is crucial for a favorable postoperative outcome. However, resection of the subcortical hyperintense zone is not essential for seizure freedom. Therefore, sparing of the subcortical white matter may reduce the surgical risk of encroaching on relevant fiber tracts. In addition, these findings give an interesting insight into the epileptogenic propensity of different parts of these lesions. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  5. Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

    NARCIS (Netherlands)

    Singh, S.; Metz, I.; Amor, S.; van der Valk, P.; Stadelmann, C.; Bruck, W.

    2013-01-01

    Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS

  6. White matter magnetic resonance hyperintensities in dementia of the Alzheimer type

    DEFF Research Database (Denmark)

    Waldemar, G; Christiansen, P; Larsson, H B

    1994-01-01

    In a prospective MRI study the presence, appearance, volume, and regional cerebral blood flow (rCBF) correlates of periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs) were examined in 18 patients with probable Alzheimer's disease and in 10 age matched healthy...... in the Alzheimer's disease group (p ... patients had extensive DWMH lesions in the central white matter. In the group of patients with Alzheimer's disease as a whole, the volume of DWMHs correlated well with rCBF in the hippocampal region ( r = -0.72; p

  7. Cognitive processing speed in older adults: relationship with white matter integrity.

    Directory of Open Access Journals (Sweden)

    Geoffrey A Kerchner

    Full Text Available Cognitive processing slows with age. We sought to determine the importance of white matter integrity, assessed by diffusion tensor imaging (DTI, at influencing cognitive processing speed among normal older adults, assessed using a novel battery of computerized, non-verbal, choice reaction time tasks. We studied 131 cognitively normal adults aged 55-87 using a cross-sectional design. Each participant underwent our test battery, as well as MRI with DTI. We carried out cross-subject comparisons using tract-based spatial statistics. As expected, reaction time slowed significantly with age. In diffuse areas of frontal and parietal white matter, especially the anterior corpus callosum, fractional anisotropy values correlated negatively with reaction time. The genu and body of the corpus callosum, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus were among the areas most involved. This relationship was not explained by gray or white matter atrophy or by white matter lesion volume. In a statistical mediation analysis, loss of white matter integrity mediated the relationship between age and cognitive processing speed.

  8. White Matter Development in Early Puberty: A Longitudinal Volumetric and Diffusion Tensor Imaging Twin Study

    NARCIS (Netherlands)

    Brouwer, R.M.; Mandl, R.C.W.; Schnack, H.G.; van Soelen, I.L.C.; van Baal, G.C.M.; Peper, J.S.; Kahn, R.S.; Boomsma, D.I.; Hulshoff Pol, H.E.

    2012-01-01

    White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and

  9. Somatotopic organization of the white matter tracts underpinning motor control in humans: an electrical stimulation study.

    Science.gov (United States)

    Rech, Fabien; Herbet, Guillaume; Moritz-Gasser, Sylvie; Duffau, Hugues

    2016-09-01

    The somatotopic organization of the primary motor cortex is well documented. However, a possible somatotopy of the network involved in motor control, i.e., eliciting negative motor phenomena during electrostimulation, is unknown in humans, particularly at the subcortical level. Here, we performed electrical stimulation mapping in awake patients operated for gliomas, to study the distribution of the white matter tracts subserving movement control of the lower limb, upper limb(s), and speech. Eighteen patients underwent awake surgery for frontal low-grade gliomas, by using intraoperative subcortical electrostimulation mapping to search interference with movement of the leg, arm(s), and face. We assessed the negative motor responses and their distribution throughout the tracts located under premotor areas. The corresponding stimulation sites were reported on a standard brain template for visual analysis and between-subjects comparisons. During stimulation of the white matter underneath the dorsal premotor cortex and supplementary motor area, rostral to the corticospinal tracts, all patients experienced cessation of the movement of lower and upper limbs, of bimanual coordination, and/or speech. These subcortical sites were somatotopically distributed. Indeed, stimulation of the fibers from mesial to lateral directions and from posterior to anterior directions evoked arrest of movement of the lower limb (mesially and posteriorly), upper limb(s), and face/speech (laterally and anteriorly). There were no postoperative permanent deficits. This is the first evidence of a somatotopic organization of the white matter bundles underpinning movement control in humans. A better knowledge of the distribution of this motor control network may be helpful in neurosciences and neurosurgery.

  10. Depressive symptoms and white matter changes in patients with dementia.

    Science.gov (United States)

    Lind, Karin; Jonsson, Michael; Karlsson, Ingvar; Sjögren, Magnus; Wallin, Anders; Edman, Ake

    2006-02-01

    The aim of the present study was to investigate if depressive symptoms in demented patients are associated with white matter changes (WMCs) in the brain. WMCs are frequently found in patients with dementia, as well as among elderly nondemented patients with depressive symptoms. However, it is less established whether or not WMCs are related to depressive symptoms in demented patients. 67 (26 men, 41 women) patients with primary degenerative dementia (Alzheimer's disease, frontotemporal dementia), vascular dementia (VaD), or mixed Alzheimer/VaD dementia were included in the study. The patients were young-old (mean 68.1, SD 7.3). All patients underwent a standardized examination procedure and MRI of the brain. The degree of WMCs was visually rated, blindly. Depressive symptoms were rated according to the Gottfries-Bråne-Steen scale (anxiety, fear-panic, depressed mood). No significant relationship was found between WMCs and depressive symptoms in the demented patients. The possible involvement of WMCs in the pathogenesis of depressive symptoms in dementia is unclear. A link between disruptions of frontal-subcortical pathways, due to WMCs, and depressive symptomatology in dementia has been hypothesised from earlier findings, which would imply common elements of pathogenesis for depressive symptomatology and cognitive impairment in dementia. However, the results of the present study do not add further support to this hypothesis. Copyright (c) 2006 John Wiley & Sons, Ltd.

  11. Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts

    Science.gov (United States)

    Berthier, Marcelo L.; De-Torres, Irene; Paredes-Pacheco, José; Roé-Vellvé, Núria; Thurnhofer-Hemsi, Karl; Torres-Prioris, María J.; Alfaro, Francisco; Moreno-Torres, Ignacio; López-Barroso, Diana; Dávila, Guadalupe

    2017-01-01

    Donepezil (DP), a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014). Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia). A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day) which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy) during 8 weeks (Endpoint 1). Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR) during 3 months (Endpoint 2). Language evaluations, diffusion weighted imaging (DWI), and voxel-based morphometry (VBM) were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these tracts. In

  12. Cholinergic Potentiation and Audiovisual Repetition-Imitation Therapy Improve Speech Production and Communication Deficits in a Person with Crossed Aphasia by Inducing Structural Plasticity in White Matter Tracts

    Directory of Open Access Journals (Sweden)

    Marcelo L. Berthier

    2017-06-01

    Full Text Available Donepezil (DP, a cognitive-enhancing drug targeting the cholinergic system, combined with massed sentence repetition training augmented and speeded up recovery of speech production deficits in patients with chronic conduction aphasia and extensive left hemisphere infarctions (Berthier et al., 2014. Nevertheless, a still unsettled question is whether such improvements correlate with restorative structural changes in gray matter and white matter pathways mediating speech production. In the present study, we used pharmacological magnetic resonance imaging to study treatment-induced brain changes in gray matter and white matter tracts in a right-handed male with chronic conduction aphasia and a right subcortical lesion (crossed aphasia. A single-patient, open-label multiple-baseline design incorporating two different treatments and two post-treatment evaluations was used. The patient received an initial dose of DP (5 mg/day which was maintained during 4 weeks and then titrated up to 10 mg/day and administered alone (without aphasia therapy during 8 weeks (Endpoint 1. Thereafter, the drug was combined with an audiovisual repetition-imitation therapy (Look-Listen-Repeat, LLR during 3 months (Endpoint 2. Language evaluations, diffusion weighted imaging (DWI, and voxel-based morphometry (VBM were performed at baseline and at both endpoints in JAM and once in 21 healthy control males. Treatment with DP alone and combined with LLR therapy induced marked improvement in aphasia and communication deficits as well as in selected measures of connected speech production, and phrase repetition. The obtained gains in speech production remained well-above baseline scores even 4 months after ending combined therapy. Longitudinal DWI showed structural plasticity in the right frontal aslant tract and direct segment of the arcuate fasciculus with both interventions. VBM revealed no structural changes in other white matter tracts nor in cortical areas linked by these

  13. Age-Related White Matter Changes

    Directory of Open Access Journals (Sweden)

    Yun Yun Xiong

    2011-01-01

    Full Text Available Age-related white matter changes (WMC are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC.

  14. Differential white matter involvement associated with distinct visuospatial deficits after right hemisphere stroke.

    Science.gov (United States)

    Carter, Alex R; McAvoy, Mark P; Siegel, Joshua S; Hong, Xin; Astafiev, Serguei V; Rengachary, Jennifer; Zinn, Kristi; Metcalf, Nicholas V; Shulman, Gordon L; Corbetta, Maurizio

    2017-03-01

    Visuospatial attention depends on the integration of multiple processes, and people with right hemisphere lesions after a stroke may exhibit severe or no visuospatial deficits. The anatomy of core components of visuospatial attention is an area of intense interest. Here we examine the relationship between the disruption of core components of attention and lesion distribution in a heterogeneous group (N = 70) of patients with right hemisphere strokes regardless of the presence of clinical neglect. Deficits of lateralized spatial orienting, measured as the difference in reaction times for responding to visual targets in the contralesional or ipsilesional visual field, and deficits in re-orienting attention, as measured by the difference in reaction times for invalidly versus validly cued targets, were measured using a computerized spatial orienting task. Both measures were related through logistic regression and a novel ridge regression method to anatomical damage measured with magnetic resonance imaging. While many regions were common to both deficit maps, a deficit in lateralized spatial orienting was more associated with lesions in the white matter underlying the posterior parietal cortex, and middle and inferior frontal gyri. A deficit in re-orienting of attention toward unattended locations was associated with lesions in the white matter of the posterior parietal cortex, insular cortex and less so with white matter involvement of the anterior frontal lobe. An hodological analysis also supports this partial dissociation between the white matter tracts that are damaged in lateralized spatial biases versus impaired re-orienting. Our results underscore that the integrity of fronto-parietal white matter tracts is crucial for visuospatial attention and that different attention components are mediated by partially distinct neuronal substrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Subcortical cerebral infarctions in sickle cell trait.

    OpenAIRE

    Reyes, M G

    1989-01-01

    At necropsy, two patients with sickle cell trait and progressive motor and visual deficits, lethargy and coma showed infarctions of the deep cerebral white matter and brain stem. The findings in these patients and another reported in the literature suggest that subcortical infarctions may be more common in sickle cell trait than has been recognised and should be suspected in any patient with sickle cell trait who presents with an unusual neurological illness.

  16. White Matter Development in Adolescence: A DTI Study

    OpenAIRE

    Asato, M. R.; Terwilliger, R.; Woo, J.; B. Luna

    2010-01-01

    Adolescence is a unique period of physical and cognitive development that includes concurrent pubertal changes and sex-based vulnerabilities. While diffusion tensor imaging (DTI) studies show white matter maturation throughout the lifespan, the state of white matter integrity specific to adolescence is not well understood as are the contributions of puberty and sex. We performed whole-brain DTI studies of 114 children, adolescents, and adults to identify age-related changes in white matter in...

  17. White matter abnormalities of microstructure and physiological noise in schizophrenia.

    Science.gov (United States)

    Cheng, Hu; Newman, Sharlene D; Kent, Jerillyn S; Bolbecker, Amanda; Klaunig, Mallory J; O'Donnell, Brian F; Puce, Aina; Hetrick, William P

    2015-12-01

    White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality.

  18. Cortical and subcortical anatomy of chronic spatial neglect following vascular damage

    Directory of Open Access Journals (Sweden)

    Schnider Armin

    2008-09-01

    Full Text Available Abstract Background The role of the inferior parietal lobule (IPL and superior temporal gyrus (STG or subcortical pathways as possible anatomical correlates of spatial neglect is currently intensely discussed. Some of the conflicting results might have arisen because patients were examined in the acute stage of disease. Methods We examined the anatomical basis of spatial neglect in a sample of patients examined in the post-acute stage following right-hemispheric vascular brain damage. Lesions of 28 patients with chronic spatial neglect were contrasted to lesions of 22 control patients without neglect using lesion subtraction techniques and voxel-wise comparisons. Results The comparisons identified the temporo-parietal junction (TPJ with underlying white matter, the supramarginal gyrus, the posterior STG, and the insula as brain regions damaged significantly more often in neglect compared to non-neglect patients. In a subgroup of neglect patients showing particularly large cancellation bias together with small errors on line bisection damage was prevalent deep in the frontal lobe while damage of patients with the reverse pattern was located in the white matter of the TPJ. Conclusion Considering our results and the findings of previous studies, spatial neglect appears to be associated with a network of regions involving the TPJ, inferior IPL, posterior STG, the insular cortex, and posterior-frontal projections. Frontal structures or projections may be of particular relevance for spatial exploration, while the IPL may be important for object-based attention as required for line bisection.

  19. Hemodynamic and metabolic correlates of perinatal white matter injury severity.

    Directory of Open Access Journals (Sweden)

    Art Riddle

    Full Text Available BACKGROUND AND PURPOSE: Although the spectrum of perinatal white matter injury (WMI in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate. METHODS: We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter. RESULTS: A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI. CONCLUSIONS: Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI.

  20. Hemodynamic and metabolic correlates of perinatal white matter injury severity.

    Science.gov (United States)

    Riddle, Art; Maire, Jennifer; Cai, Victor; Nguyen, Thuan; Gong, Xi; Hansen, Kelly; Grafe, Marjorie R; Hohimer, A Roger; Back, Stephen A

    2013-01-01

    Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate. We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter. A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI. Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI.

  1. White matter tracts of speech and language.

    Science.gov (United States)

    Smits, Marion; Jiskoot, Lize C; Papma, Janne M

    2014-10-01

    Diffusion tensor imaging (DTI) has been used to investigate the white matter (WM) tracts underlying the perisylvian cortical regions known to be associated with language function. The arcuate fasciculus is composed of 3 segments (1 long and 2 short) whose separate functions correlate with traditional models of conductive and transcortical motor or sensory aphasia, respectively. DTI mapping of language fibers is useful in presurgical planning for patients with dominant hemisphere tumors, particularly when combined with functional magnetic resonance imaging. DTI has found damage to language networks in stroke patients and has the potential to influence poststroke rehabilitation and treatment. Assessment of the WM tracts involved in the default mode network has been found to correlate with mild cognitive impairment, potentially explaining language deficits in patients with apparently mild small vessel ischemic disease. Different patterns of involvement of language-related WM structures appear to correlate with different clinical subtypes of primary progressive aphasias. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Evidence for Functional Networks within the Human Brain's White Matter.

    Science.gov (United States)

    Peer, Michael; Nitzan, Mor; Bick, Atira S; Levin, Netta; Arzy, Shahar

    2017-07-05

    Investigation of the functional macro-scale organization of the human cortex is fundamental in modern neuroscience. Although numerous studies have identified networks of interacting functional modules in the gray-matter, limited research was directed to the functional organization of the white-matter. Recent studies have demonstrated that the white-matter exhibits blood oxygen level-dependent signal fluctuations similar to those of the gray-matter. Here we used these signal fluctuations to investigate whether the white-matter is organized as functional networks by applying a clustering analysis on resting-state functional MRI (RSfMRI) data from white-matter voxels, in 176 subjects (of both sexes). This analysis indicated the existence of 12 symmetrical white-matter functional networks, corresponding to combinations of white-matter tracts identified by diffusion tensor imaging. Six of the networks included interhemispheric commissural bridges traversing the corpus callosum. Signals in white-matter networks correlated with signals from functional gray-matter networks, providing missing knowledge on how these distributed networks communicate across large distances. These findings were replicated in an independent subject group and were corroborated by seed-based analysis in small groups and individual subjects. The identified white-matter functional atlases and analysis codes are available at http://mind.huji.ac.il/white-matter.aspx Our results demonstrate that the white-matter manifests an intrinsic functional organization as interacting networks of functional modules, similarly to the gray-matter, which can be investigated using RSfMRI. The discovery of functional networks within the white-matter may open new avenues of research in cognitive neuroscience and clinical neuropsychiatry.SIGNIFICANCE STATEMENT In recent years, functional MRI (fMRI) has revolutionized all fields of neuroscience, enabling identifications of functional modules and networks in the human

  3. Associations between self‐reported sleep quality and white matter in community‐dwelling older adults: A prospective cohort study

    Science.gov (United States)

    Zsoldos, Enikő; Filippini, Nicola; Griffanti, Ludovica; Winkler, Anderson; Mahmood, Abda; Allan, Charlotte L.; Topiwala, Anya; Kyle, Simon D.; Spiegelhalder, Kai; Singh‐Manoux, Archana; Kivimaki, Mika; Mackay, Clare E.; Johansen‐Berg, Heidi; Ebmeier, Klaus P.

    2017-01-01

    Abstract Both sleep disturbances and decline in white matter microstructure are commonly observed in ageing populations, as well as in age‐related psychiatric and neurological illnesses. A relationship between sleep and white matter microstructure may underlie such relationships, but few imaging studies have directly examined this hypothesis. In a study of 448 community‐dwelling members of the Whitehall II Imaging Sub‐Study aged between 60 and 82 years (90 female, mean age 69.2 ± 5.1 years), we used the magnetic resonance imaging technique diffusion tensor imaging to examine the relationship between self‐reported sleep quality and white matter microstructure. Poor sleep quality at the time of the diffusion tensor imaging scan was associated with reduced global fractional anisotropy and increased global axial diffusivity and radial diffusivity values, with small effect sizes. Voxel‐wise analysis showed that widespread frontal‐subcortical tracts, encompassing regions previously reported as altered in insomnia, were affected. Radial diffusivity findings remained significant after additional correction for demographics, general cognition, health, and lifestyle measures. No significant differences in general cognitive function, executive function, memory, or processing speed were detected between good and poor sleep quality groups. The number of times participants reported poor sleep quality over five time‐points spanning a 16‐year period was not associated with white matter measures. In conclusion, these data demonstrate that current sleep quality is linked to white matter microstructure. Small effect sizes may limit the extent to which poor sleep is a promising modifiable factor that may maintain, or even improve, white matter microstructure in ageing. Hum Brain Mapp 38:5465–5473, 2017. © 2017 Wiley Periodicals, Inc. PMID:28745016

  4. White Matter Injury and Recovery after Hypertensive Intracerebral Hemorrhage

    Science.gov (United States)

    Zuo, Shilun; Pan, Pengyu; Li, Qiang

    2017-01-01

    Hypertensive intracerebral hemorrhage (ICH) could very probably trigger white matter injury in patients. Through the continuous study of white matter injury after hypertensive ICH, we achieve a more profound understanding of the pathophysiological mechanism of its occurrence and development. At the same time, we found a series of drugs and treatment methods for the white matter repair. In the current reality, the research paradigm of white matter injury after hypertensive ICH is relatively obsolete or incomplete, and there are still lots of deficiencies in the research. In the face of the profound changes of stroke research perspective, we believe that the combination of the lenticulostriate artery, nerve nuclei of the hypothalamus-thalamus-basal ganglia, and the white matter fibers located within the capsula interna will be beneficial to the research of white matter injury and repair. This paper has classified and analyzed the study of white matter injury and repair after hypertensive ICH and also rethought the shortcomings of the current research. We hope that it could help researchers further explore and study white matter injury and repair after hypertensive ICH. PMID:28680884

  5. Motor versus body awareness: Voxel-based lesion analysis in anosognosia for hemiplegia and somatoparaphrenia following right hemisphere stroke.

    Science.gov (United States)

    Moro, Valentina; Pernigo, Simone; Tsakiris, Manos; Avesani, Renato; Edelstyn, Nicola M J; Jenkinson, Paul M; Fotopoulou, Aikaterini

    2016-10-01

    Anosognosia for hemiplegia (AHP) is informative about the neurocognitive basis of motor awareness. However, it is frequently associated with concomitant symptoms, such as hemispatial neglect and disturbances in the sense of body ownership (DSO). Although double dissociations between these symptoms have been reported, there is ongoing debate about whether they are manifestations of independent abnormalities, or a single neurocognitive deficit. We aimed to investigate the specificity of lesions associated with AHP by surpassing four, existing methodological limitations: (a) recruit a relatively large sample of patients (total N = 70) in a multi-centre study; (b) identify lesions associated with AHP in grey and white matter using voxel-based methods; (c) take into account the duration of AHP and concomitant neglect symptoms; and (d) compare lesions against a control hemiplegic group, patients suffering from AHP and DSO, and a few, rare patients with selective DSO. Results indicated that acute AHP is associated with a wide network, mainly including: (1) the Rolandic operculum, (2) the insula and (3) the superior temporal gyri. Subcortically, damage mainly involved the basal ganglia and white matter, mostly the superior corona radiate, arcuate fasciculus and the part of the ventral, superior longitudinal fasciculus. Persistent symptoms were linked with wider damage involving fronto-temporal cortex and long white matter tracts. A shift in the latero-medial direction (mainly involving the basal ganglia and surrounding white matter) emerged when DSO was taken accounted for. These results suggest that while bodily awareness is processed by areas widely distributed across the brain, intact subcortical structures and white matter tracts may be necessary to support basic feelings of owning and controlling contralateral body parts. An accurate and 'up-to-date' awareness of our motor abilities, however, may rely also on intact processing in cortical areas which presumably

  6. Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects

    Directory of Open Access Journals (Sweden)

    Patrick Schiffler

    2017-07-01

    Full Text Available The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner.

  7. Convection-enhanced delivery of AAV2 in white matter--a novel method for gene delivery to cerebral cortex.

    Science.gov (United States)

    Barua, N U; Woolley, M; Bienemann, A S; Johnson, D; Wyatt, M J; Irving, C; Lewis, O; Castrique, E; Gill, S S

    2013-10-30

    Convection-enhanced delivery (CED) is currently under investigation for delivering therapeutic agents to subcortical targets in the brain. Direct delivery of therapies to the cerebral cortex, however, remains a significant challenge. We describe a novel method of targeting adeno-associated viral vector (AAV) mediated gene therapies to specific cerebral cortical regions by performing high volume, high flow rate infusions into underlying white matter in a large animal (porcine) model. Infusion volumes of up to 700 μl at flow rates as high as 10 μl/min were successfully performed in white matter without adverse neurological sequelae. Co-infusion of AAV2/5-GFP with 0.2% Gadolinium in artificial CSF confirmed transgene expression in the deep layers of cerebral cortex overlying the infused areas of white matter. AAV-mediated gene therapies have been previously targeted to the cerebral cortex by performing intrathalamic CED and exploiting axonal transport. The novel method described in this study facilitates delivery of gene therapies to specific regions of the cerebral cortex without targeting deep brain structures. AAV-mediated gene therapies can be targeted to specific cortical regions by performing CED into underlying white matter. This technique could be applied to the treatment of neurological disorders characterised by cerebral cortical degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Motor recovery and microstructural change in rubro-spinal tract in subcortical stroke.

    Science.gov (United States)

    Takenobu, Yohei; Hayashi, Takuya; Moriwaki, Hiroshi; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Fukuyama, Hidenao

    2014-01-01

    The mechanism of motor recovery after stroke may involve reorganization of the surviving networks. However, details of adaptive changes in structural connectivity are not well understood. Here, we show long-term changes in white matter microstructure that relate to motor recovery in stroke patients. We studied ten subcortical ischemic stroke patients who showed motor hemiparesis at the initial clinical examination and an infarcted lesion centered in the posterior limb of internal capsule of the unilateral hemisphere at the initial diffusion-weighted magnetic resonance imaging scan. The participants underwent serial diffusion tensor imaging and motor function assessments at three consecutive time points; within 2 weeks, and at 1 and 3 months after the onset. Fractional anisotropy (FA) was analyzed for regional differences between hemispheres and time points, as well as for correlation with motor recovery using a tract-based spatial statistics analysis. The results showed significantly increased FA in the red nucleus and dorsal pons in the ipsi-lesional side at 3 months, and significantly decreased FA in the ipsi-lesional internal capsule at all time points, and in the cerebral peduncle, corona radiata, and corpus callosum at 3 months. In the correlation analysis, FA values of clusters in the red nucleus, dorsal pons, midbody of corpus callosum, and cingulum were positively correlated with recovery of motor function. Our study suggests that changes in white matter microstructure in alternative descending motor tracts including the rubro-spinal pathway, and interhemispheric callosal connections may play a key role in compensating for motor impairment after subcortical stroke.

  9. Differential diagnosis of white matter diseases in the tropics: An overview

    Directory of Open Access Journals (Sweden)

    Pandit Lekha

    2009-01-01

    Full Text Available In hospitals in the tropics, the availability of magnetic resonance imaging (MRI facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV infection tops the list of infective conditions. Central nervous system (CNS tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke′s encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics.

  10. Regional staging of white matter signal abnormalities in aging and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Emily R. Lindemer

    2017-01-01

    Full Text Available White matter lesions, quantified as ‘white matter signal abnormalities’ (WMSA on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic ‘staging’ of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC aged 52–90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I–IV. A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals

  11. Regional staging of white matter signal abnormalities in aging and Alzheimer's disease.

    Science.gov (United States)

    Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce R; Augustinack, Jean C; Salat, David H

    2017-01-01

    White matter lesions, quantified as 'white matter signal abnormalities' (WMSA) on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic 'staging' of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC) aged 52-90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I-IV). A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals with Alzheimer's disease

  12. Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI

    Energy Technology Data Exchange (ETDEWEB)

    Brockmann, K.; Hanefeld, F. [Dept. of Paediatrics and Neuropaediatrics, Children' s Hospital, Georg-August-Univ., Goettingen (Germany); Finsterbusch, J.; Frahm, J. [Biomedizinische NMR Forschungs GmbH am Max-Planck-Inst. fuer biophysikalische Chemie, Goettingen (Germany); Terwey, B. [Inst. fuer Magnet-Resonanz-Diagnostik, Zentralkrankenhaus, Bremen (Germany)

    2003-03-01

    A 37-year-old macrocephalic woman was investigated for increasing gait disturbance due to longstanding spasticity and ataxia. MRI showed widespread bilateral increase in signal from cerebral white matter on T2-weighted images. Numerous subcortical cysts were visible in anterior-temporal and parietal regions. These clinical and neuroradiological features are those of megalencephalic leukoencephalopathy with subcortical cysts (MLC), a recently delineated white-matter disease with onset in childhood. Quantitative localised proton MR spectroscopy of white matter revealed marked reduction of N-acetylaspartate, creatine, and choline with normal values for myoinositol, consistent with axonal loss and astrocytic proliferation. Diffusion tensor imaging showed an increased apparent diffusion coefficient and reduced anisotropy in affected white matter pointing to reduced cell density with an increased extracellular space. These findings are in line with histological changes alterations known to occur in MLC. (orig.)

  13. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  14. Tryptophan Metabolism and White Matter Integrity in Schizophrenia.

    Science.gov (United States)

    Chiappelli, Joshua; Postolache, Teodor T; Kochunov, Peter; Rowland, Laura M; Wijtenburg, S Andrea; Shukla, Dinesh K; Tagamets, Malle; Du, Xiaoming; Savransky, Anya; Lowry, Christopher A; Can, Adem; Fuchs, Dietmar; Hong, L Elliot

    2016-09-01

    Schizophrenia is associated with abnormalities in the structure and functioning of white matter, but the underlying neuropathology is unclear. We hypothesized that increased tryptophan degradation in the kynurenine pathway could be associated with white matter microstructure and biochemistry, potentially contributing to white matter abnormalities in schizophrenia. To test this, fasting plasma samples were obtained from 37 schizophrenia patients and 38 healthy controls and levels of total tryptophan and its metabolite kynurenine were assessed. The ratio of kynurenine to tryptophan was used as an index of tryptophan catabolic activity in this pathway. White matter structure and function were assessed by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS). Tryptophan levels were significantly lower (ptryptophan ratios were correspondingly higher (p=0.018) in patients compared with controls. In patients, lower plasma tryptophan levels corresponded to lower structural integrity (DTI fractional anisotropy) (r=0.347, p=0.038). In both patients and controls, the kynurenine/tryptophan ratio was inversely correlated with frontal white matter glutamate level (r=-0.391 and -0.350 respectively, p=0.024 and 0.036). These results provide initial evidence implicating abnormal tryptophan/kynurenine pathway activity in changes to white matter integrity and white matter glutamate in schizophrenia.

  15. Abnormal white matter properties in adolescent girls with anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Katherine E. Travis

    2015-01-01

    Full Text Available Anorexia nervosa (AN is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1, an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4 were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3. We identified and segmented 9 bilateral cerebral tracts (18 and 8 callosal fiber tracts in each participant's brain (26 total. Tract profiles were generated by computing measures for fractional anisotropy (FA and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.

  16. Superficial white matter damage in anti-NMDA receptor encephalitis.

    Science.gov (United States)

    Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

    2017-11-03

    Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Subcortical Low-Intensity Lesions on Fluid-Attenuated Inversion Recovery Images After Revascularization Surgery for Moyamoya Disease.

    Science.gov (United States)

    Machida, Toshio; Nakano, Shigeki; Ishige, Satoshi; Ono, Junichi; Fujikawa, Atsushi

    2017-02-01

    Although uncommon, subcortical low-intensity (SCLI) changes on fluid-attenuated inversion recovery images are observed in various diseases, including cerebral ischemia. Here, we aimed to clarify the incidence and clinical implications of SCLI changes after revascularization surgery for moyamoya disease, focusing on the correlation with postoperative transient neurologic events (TNEs). In this retrospective case series analysis, we included 10 hemispheres from 9 adults with moyamoya disease who underwent revascularization surgery. Subcortical signal intensity at the 5 gyri around the anastomosis point was quantitatively measured at 1 week and 3 months postoperatively. Changes in cerebral blood flow (CBF) were assessed using single-photon emission computed tomography. Images taken 1 week after surgery showed widespread SCLI changes below the operative fields in all 10 cases, but these changes normalized by 3 months. In addition, the changes in signal intensity at anastomoses negatively correlated with the changes in CBF (R(2) = 0.36; P = 0.039). Postoperative TNEs occurred in 6 cases (60%) but were resolved within 17 days after surgery. Postoperative CBF increased in 9 of the 10 cases, with a median of 23%; however, these increases were not associated with the development of TNEs. The SCLI changes at the anastomosis points did not differ by the experience of TNEs. Early after surgery, SCLI changes are common findings below the operative fields but negatively correlate with increases in CBF. Although no significant association was found between TNEs and the SCLI changes, the synchronized development of these phenomena may suggest a common underlying pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Automatic histogram-based segmentation of white matter hyperintensities using 3D FLAIR images

    Science.gov (United States)

    Simões, Rita; Slump, Cornelis; Moenninghoff, Christoph; Wanke, Isabel; Dlugaj, Martha; Weimar, Christian

    2012-03-01

    White matter hyperintensities are known to play a role in the cognitive decline experienced by patients suffering from neurological diseases. Therefore, accurately detecting and monitoring these lesions is of importance. Automatic methods for segmenting white matter lesions typically use multimodal MRI data. Furthermore, many methods use a training set to perform a classification task or to determine necessary parameters. In this work, we describe and evaluate an unsupervised segmentation method that is based solely on the histogram of FLAIR images. It approximates the histogram by a mixture of three Gaussians in order to find an appropriate threshold for white matter hyperintensities. We use a context-sensitive Expectation-Maximization method to determine the Gaussian mixture parameters. The segmentation is subsequently corrected for false positives using the knowledge of the location of typical FLAIR artifacts. A preliminary validation with the ground truth on 6 patients revealed a Similarity Index of 0.73 +/- 0.10, indicating that the method is comparable to others in the literature which require multimodal MRI and/or a preliminary training step.

  19. White matter tract integrity in treatment-resistant gambling disorder

    DEFF Research Database (Denmark)

    Chamberlain, Samuel R.; Derbyshire, Katherine; Daws, Richard E.

    2016-01-01

    Background: Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of ‘substance-related and addictive disorders’. Aims: To compare white matter integrity in patients with gambling disorder with healthy controls; to explore...... relationships between white matter integrity and disease severity in gambling disorder. Method: In total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics....... Results: Gambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity. Conclusions: Reduced corpus callosum fractional...

  20. Hemodynamic and metabolic correlates of perinatal white matter injury severity

    National Research Council Canada - National Science Library

    Riddle, Art; Maire, Jennifer; Cai, Victor; Nguyen, Thuan; Gong, Xi; Hansen, Kelly; Grafe, Marjorie R; Hohimer, A Roger; Back, Stephen A

    2013-01-01

    Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear...

  1. Fiber tracking of brain white matter based on graph theory.

    Science.gov (United States)

    Lu, Meng

    2015-01-01

    Brain white matter tractography is reconstructed via diffusion-weighted magnetic resonance images. Due to the complex structure of brain white matter fiber bundles, fiber crossing and fiber branching are abundant in human brain. And regular methods with diffusion tensor imaging (DTI) can't accurately handle this problem. the biggest problems of the brain tractography. Therefore, this paper presented a novel brain white matter tractography method based on graph theory, so the fiber tracking between two voxels is transformed into locating the shortest path in a graph. Besides, the presented method uses Q-ball imaging (QBI) as the source data instead of DTI, because QBI can provide accurate information about multiple fiber crossing and branching in one voxel using orientation distribution function (ODF). Experiments showed that the presented method can accurately handle the problem of brain white matter fiber crossing and branching, and reconstruct brain tractograhpy both in phantom data and real brain data.

  2. Chemotherapy-induced cognitive impairments: White matter pathologies.

    Science.gov (United States)

    Matsos, A; Loomes, M; Zhou, I; Macmillan, E; Sabel, I; Rotziokos, E; Beckwith, W; Johnston, I N

    2017-12-01

    Whilst chemotherapeutic agents show promising results in the amelioration of cancerous tumors, patients often experience cognitive disturbances associated with chemotherapy long after treatment has ceased. Research has suggested that the structural integrity of white matter fibres in the brain are susceptible to the harmful effects of chemotherapy. Post-chemotherapy, white matter tracts often display altered morphology with a reduction in glial cells such as oligodendrocytes. Demyelination, gliosis and leukoencephalopathy during or post chemotherapy is associated with changes in processing speed and IQ. Thus, understanding the relationship between chemotherapy, white matter damage and cognition is warranted. This review presents evidence for chemotherapy induced white matter damage highlighting the importance of implementing behavioral and pharmological strategies to prevent or reverse such acute toxicity in the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. White matter disease and an incomplete circle of Willis.

    Science.gov (United States)

    Ryan, Daniel James; Byrne, Susan; Dunne, Ruth; Harmon, Mark; Harbison, Joseph

    2015-06-01

    White matter disease occurs as a consequence of small vessel disease; however, hypoperfusion may also play a role. We investigated whether patients with less cerebral vessel anastomosis may develop more white matter disease. Magnetic resonance imaging (1.5t) with intracranial magnetic resonance angiography data was collected on a convenience sample between July 2008 and January 2009. All patients were independently assessed for circle of Willis variants by two researchers and categorized into two groups: those with a complete circle of Willis and those with an incomplete circle of Willis (absent vessels). The complete group was sub-divided into a classical group (entirely normal circle of Willis) and a hypoplastic group (hypoplasia but no absent vessels). White matter disease assessment was conducted for these groups, by two researchers blind to magnetic resonance angiography findings, on all patients over 50 years old. The circle of Willis was characterized in 163 patients, while 90 (>50 years) underwent white matter disease assessment. The kappa inter-rater reliability between both circle of Willis assessors and between both white matter disease assessors was 0.57 and 0.63, respectively. The prevalence of circle of Willis variants strongly correlated with the seminal paper by Riggs and Rupp. Independent of age and gender, those with an incomplete circle of Willis (n = 68) exhibited 58% more white matter disease than those with a complete circle of Willis (n = 22) (white matter disease score 6.52 vs. 4.11, respectively, P = 0.03). Patients with absent anterior vessels exhibited more frontal white matter disease than those with intact anterior vessels (3.7 vs. 1.72, P < 0.001). Patients with absent posterior vessels exhibited more occipital white matter disease than those with intact posterior vessels (2.52 vs. 1.34, P = 0.014). These data suggest that congenital absence of anastomotic capacity correlates with incident white matter disease, thus

  4. Diminished white matter integrity in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Tobias Schmidt-Wilcke

    2014-01-01

    Conclusions: Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

  5. White matter pathways associated with working memory in normal aging.

    Science.gov (United States)

    Charlton, Rebecca A; Barrick, Thomas R; Lawes, I Nigel C; Markus, Hugh S; Morris, Robin G

    2010-04-01

    Previous studies by our group have found that white matter integrity as determined by Diffusion Tensor Imaging (DTI) is associated with working memory decline. It has been proposed that subtle white matter integrity loss may lead to the disruption of working memory in particular because it relies on the dynamic and reiterative activity of cortico-cortical pathways. DTI and working memory measurement were acquired for 99 adults from our GENIE study of healthy middle aged and elderly individuals. Voxel-based statistics were used to identify clusters of voxels in mean diffusivity images specifically associated with variations in working memory performance. Tractography then identified the cortico-cortical white matter pathways passing through these clusters, between the temporal, parietal and frontal cortices. Significant clusters were identified which were associated with working memory in the white matter of the temporal and frontal lobes, the cingulate gyrus, and in the thalamus. The tracts that passed through these clusters included the superior parietal lobule pathway, the medial temporo-frontal pathway, the uncinate fasciculus, the fronto-parietal fasciculus, and the cingulum. Significant clusters were identified in the white matter that were associated with working memory performance. Tractography performed through these clusters identified white matter fiber tracts which pass between grey matter regions known to be activated by working memory tasks and also mirror working memory pathways suggested by previous functional connectivity imaging. Copyright 2009 Elsevier Srl. All rights reserved.

  6. White matter development in adolescence: a DTI study.

    Science.gov (United States)

    Asato, M R; Terwilliger, R; Woo, J; Luna, B

    2010-09-01

    Adolescence is a unique period of physical and cognitive development that includes concurrent pubertal changes and sex-based vulnerabilities. While diffusion tensor imaging (DTI) studies show white matter maturation throughout the lifespan, the state of white matter integrity specific to adolescence is not well understood as are the contributions of puberty and sex. We performed whole-brain DTI studies of 114 children, adolescents, and adults to identify age-related changes in white matter integrity that characterize adolescence. A distinct set of regions across the brain were found to have decreasing radial diffusivity across age groups. Region of interest analyses revealed that maturation was attained by adolescence in broadly distributed association and projection fibers, including those supporting cortical and brain stem integration that may underlie known enhancements in reaction time during this period. Maturation after adolescence included association and projection tracts, including prefrontal-striatal connections, known to support top-down executive control of behavior and interhemispheric connectivity. Maturation proceeded in parallel with pubertal changes to the postpubertal stage, suggesting hormonal influences on white matter development. Females showed earlier maturation of white matter integrity compared with males. Together, these findings suggest that white matter connectivity supporting executive control of behavior is still immature in adolescence.

  7. Factors involved in inflammation-induced developmental white matter damage.

    Science.gov (United States)

    Stolp, Helen B; Ek, C Joakim; Johansson, Pia A; Dziegielewska, Katarzyna M; Bethge, Nicole; Wheaton, Benjamin J; Potter, Ann M; Saunders, Norman R

    2009-02-27

    Developmental white matter damage is a brain pathology associated with several long-term neurological disorders. An inflammatory insult has been suggested as the major instigating event. This study investigated the relative influence of inflammation, blood-brain barrier permeability and glial ontogeny in white matter damage. Systemic inflammation was induced in Monodelphis domestica (opossum) by serial intraperitoneal injections of lipopolysaccharide at different stages of brain development. Volume of white matter was estimated for the external capsule. Blood-brain barrier permeability was assessed immunocytochemically. Quantitative RT-PCR was used to measure relative levels of mRNA for IL-1beta, IL-6 and COX-2. Developmental changes in numbers and appearance of microglia and astrocytes were estimated. Results showed that in response to systemic inflammation, white matter was reduced in the external capsule during a circumscribed period only. At the same developmental stage blood-brain barrier permeability was altered, cerebral inflammatory response was present and numbers of microglia increased. However, the periods of altered blood-brain barrier permeability and the cerebral inflammatory response were longer than the period of the external capsule's susceptibility to white matter damage, which coincided with the developmental increase in the number of astrocytes in this tract. Thus, the mechanism of white matter damage following systemic inflammation is multifactorial, including cerebral inflammation and breakdown of brain barriers occurring simultaneously at specific stages of glial cell development.

  8. Individual differences in EEG spectral power reflect genetic variance in gray and white matter volumes.

    Science.gov (United States)

    Smit, Dirk J A; Boomsma, Dorret I; Schnack, Hugo G; Hulshoff Pol, Hilleke E; de Geus, Eco J C

    2012-06-01

    The human electroencephalogram (EEG) consists of oscillations that reflect the summation of postsynaptic potentials at the dendritic tree of cortical neurons. The strength of the oscillations (EEG power) is a highly genetic trait that has been related to individual differences in many phenotypes, including intelligence and liability for psychopathology. Here, we investigated whether brain anatomy underlies these EEG power differences by correlating it to gray and white matter volumes (GMV, WMV), and additionally investigated whether this association can be attributed to genes or environmental factors. EEG was measured in a sample of 405 young adult twins and their siblings, and power in the theta (~4 Hz), alpha (~10 Hz), and beta (~20 Hz) frequency bands determined. A subset of 121 subjects were also scanned in a 1.5 T MRI scanner, and gray and white matter volumes defined as the total of cortical and subcortical volumes, excluding cerebellum. Both MRI-based volumes and EEG power spectra were highly heritable. GMV and WMV correlated .25 to .29 with EEG power for the slower oscillations (theta, alpha). Moreover, these phenotypic correlations largely reflected genetic covariation, irrespective of oscillation frequency and volume type. Genetic correlations (.31 genetic sources of variation, which may reflect such processes as myelination, synaptic density, and dendritic outgrowth.

  9. Epigenetic Age Acceleration Assessed with Human White-Matter Images.

    Science.gov (United States)

    Hodgson, Karen; Carless, Melanie A; Kulkarni, Hemant; Curran, Joanne E; Sprooten, Emma; Knowles, Emma E; Mathias, Samuel; Göring, Harald H H; Yao, Nailin; Olvera, Rene L; Fox, Peter T; Almasy, Laura; Duggirala, Ravi; Blangero, John; Glahn, David C

    2017-05-03

    The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic age was estimated using the method developed by Horvath (2013). For n = 376 individuals, diffusion tensor imaging scans were also available. The interrelationship between epigenetic age acceleration and global white matter integrity was investigated with variance decomposition methods. To test for neuroanatomical specificity, 16 specific tracts were additionally considered. We observed negative phenotypic correlations between epigenetic age acceleration and global white matter tract integrity (ρpheno = -0.119, p = 0.028), with evidence of shared genetic (ρgene = -0.463, p = 0.013) but not environmental influences. Negative phenotypic and genetic correlations with age acceleration were also seen for a number of specific white matter tracts, along with additional negative phenotypic correlations between granulocyte abundance and white matter integrity. These findings (i.e., increased acceleration in epigenetic age in peripheral blood correlates with reduced white matter integrity in the brain and shares common genetic influences) provide a window into the neurobiology of aging processes within the brain and a potential biomarker of normal and pathological brain aging.SIGNIFICANCE STATEMENT Epigenetic measures can be used to predict age with a high degree of accuracy and so

  10. Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation

    Directory of Open Access Journals (Sweden)

    van Horssen Jack

    2012-07-01

    Full Text Available Abstract Background In brain tissues from multiple sclerosis (MS patients, clusters of activated HLA-DR-expressing microglia, also referred to as preactive lesions, are located throughout the normal-appearing white matter. The aim of this study was to gain more insight into the frequency, distribution and cellular architecture of preactive lesions using a large cohort of well-characterized MS brain samples. Methods Here, we document the frequency of preactive lesions and their association with distinct white matter lesions in a cohort of 21 MS patients. Immunohistochemistry was used to gain further insight into the cellular and molecular composition of preactive lesions. Results Preactive lesions were observed in a majority of MS patients (67% irrespective of disease duration, gender or subtype of disease. Microglial clusters were predominantly observed in the vicinity of active demyelinating lesions and are not associated with T cell infiltrates, axonal alterations, activated astrocytes or blood–brain barrier disruption. Microglia in preactive lesions consistently express interleukin-10 and TNF-α, but not interleukin-4, whereas matrix metalloproteases-2 and −9 are virtually absent in microglial nodules. Interestingly, key subunits of the free-radical-generating enzyme NADPH oxidase-2 were abundantly expressed in microglial clusters. Conclusions The high frequency of preactive lesions suggests that it is unlikely that most of them will progress into full-blown demyelinating lesions. Preactive lesions are not associated with blood–brain barrier disruption, suggesting that an intrinsic trigger of innate immune activation, rather than extrinsic factors crossing a damaged blood–brain barrier, induces the formation of clusters of activated microglia.

  11. Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI variables.

    Science.gov (United States)

    Kim, Geon Ha; Lee, Jae Hong; Seo, Sang Won; Ye, Byoung Seok; Cho, Hanna; Kim, Hee Jin; Noh, Young; Yoon, Cindy W; Chin, Ju Hee; Oh, Seung Jun; Kim, Jae Seung; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Jeong, Jee Hyang; Na, Duk L

    2014-04-29

    The purpose of this study was to propose new criteria for differentiating Pittsburgh compound B (PiB)-negative from PiB-positive subcortical vascular dementia (SVaD) using clinical and MRI variables. We measured brain amyloid deposition using PiB-PET in 77 patients with SVaD. All patients met DSM-IV criteria for vascular dementia and had severe white matter hyperintensities on MRI, defined as a cap or band ≥ 10 mm as well as a deep white matter lesion ≥ 25 mm. Eleven models were considered to differentiate PiB(-) from PiB(+) SVaD using 4 variables, including age, number of lacunes, medial temporal atrophy (MTA), and APOE ε4. The ideal cutoff values in each of the 11 models were selected using the highest Youden index. A total of 49 of 77 patients (63.6%) tested negative for PiB retention, while 28 (36.4%) tested positive for PiB retention. The ideal model for differentiating PiB(-) from PiB(+) SVaD was as follows: age ≤ 75 years, ≥ 5 lacunes, and MTA ≤ 3, which together yielded an accuracy of 67.5%. When patients meet the DSM-IV criteria for vascular dementia and also have severe white matter hyperintensities, younger age, greater number of lacunes, and lesser MTA, these are predictive of a PiB(-) scan in patients with SVaD. This study provides Class II evidence that the combination of younger age, greater number of lacunes, and lesser MTA identifies patients with SVaD at lower risk of Alzheimer disease pathology.

  12. Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia.

    Science.gov (United States)

    Meinzer, Marcus; Mohammadi, Siawoosh; Kugel, Harald; Schiffbauer, Hagen; Flöel, Agnes; Albers, Johannes; Kramer, Kira; Menke, Ricarda; Baumgärtner, Annette; Knecht, Stefan; Breitenstein, Caterina; Deppe, Michael

    2010-10-15

    Aphasia after middle cerebral artery (MCA) stroke shows highly variable degrees of recovery. One possible explanation may be offered by the variability of the occlusion location. Branches from the proximal portion of the MCA often supply the mesial temporal lobe including parts of the hippocampus, a structure known to be involved in language learning. Therefore, we assessed whether language recovery in chronic aphasia is dependent on the proximity of the MCA infarct and correlated with the integrity of the hippocampus and its surrounding white matter. Language reacquisition capability was determined after 2weeks of intensive language therapy and 8months after treatment in ten chronic aphasia patients. Proximity of MCA occlusion relative to the internal carotid artery was determined by magnetic resonance imaging (MRI) based on the most proximal anatomical region infarcted. Structural damage to the hippocampus was assessed by MRI-based volumetry, regional microstructural integrity of hippocampus adjacent white matter by fractional anisotropy. Language learning success for trained materials was correlated with the proximity of MCA occlusion, microstructural integrity of the left hippocampus and its surrounding white matter, but not with lesion size, overall microstructural brain integrity and a control region outside of the MCA territory. No correlations were found for untrained language materials, underlining the specificity of our results for training-induced recovery. Our results suggest that intensive language therapy success in chronic aphasia after MCA stroke is critically dependent on damage to the hippocampus and its surrounding structures. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Framework for shape analysis of white matter fiber bundles.

    Science.gov (United States)

    Glozman, Tanya; Bruckert, Lisa; Pestilli, Franco; Yecies, Derek W; Guibas, Leonidas J; Yeom, Kristen W

    2017-12-02

    Diffusion imaging coupled with tractography algorithms allows researchers to image human white matter fiber bundles in-vivo. These bundles are three-dimensional structures with shapes that change over time during the course of development as well as in pathologic states. While most studies on white matter variability focus on analysis of tissue properties estimated from the diffusion data, e.g. fractional anisotropy, the shape variability of white matter fiber bundle is much less explored. In this paper, we present a set of tools for shape analysis of white matter fiber bundles, namely: (1) a concise geometric model of bundle shapes; (2) a method for bundle registration between subjects; (3) a method for deformation estimation. Our framework is useful for analysis of shape variability in white matter fiber bundles. We demonstrate our framework by applying our methods on two datasets: one consisting of data for 6 normal adults and another consisting of data for 38 normal children of age 11 days to 8.5 years. We suggest a robust and reproducible method to measure changes in the shape of white matter fiber bundles. We demonstrate how this method can be used to create a model to assess age-dependent changes in the shape of specific fiber bundles. We derive such models for an ensemble of white matter fiber bundles on our pediatric dataset and show that our results agree with normative human head and brain growth data. Creating these models for a large pediatric longitudinal dataset may improve understanding of both normal development and pathologic states and propose novel parameters for the examination of the pediatric brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

    Science.gov (United States)

    Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

    2017-01-01

    Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  15. White matter predicts functional connectivity in premanifest Huntington's disease.

    Science.gov (United States)

    McColgan, Peter; Gregory, Sarah; Razi, Adeel; Seunarine, Kiran K; Gargouri, Fatma; Durr, Alexandra; Roos, Raymund A C; Leavitt, Blair R; Scahill, Rachael I; Clark, Chris A; Tabrizi, Sarah J; Rees, Geraint; Coleman, A; Decolongon, J; Fan, M; Petkau, T; Jauffret, C; Justo, D; Lehericy, S; Nigaud, K; Valabrègue, R; Choonderbeek, A; Hart, E P T; Hensman Moss, D J; Crawford, H; Johnson, E; Papoutsi, M; Berna, C; Reilmann, R; Weber, N; Stout, J; Labuschagne, I; Landwehrmeyer, B; Orth, M; Johnson, H

    2017-02-01

    The distribution of pathology in neurodegenerative disease can be predicted by the organizational characteristics of white matter in healthy brains. However, we have very little evidence for the impact these pathological changes have on brain function. Understanding any such link between structure and function is critical for understanding how underlying brain pathology influences the progressive behavioral changes associated with neurodegeneration. Here, we demonstrate such a link between structure and function in individuals with premanifest Huntington's. Using diffusion tractography and resting state functional magnetic resonance imaging to characterize white matter organization and functional connectivity, we investigate whether characteristic patterns of white matter organization in the healthy human brain shape the changes in functional coupling between brain regions in premanifest Huntington's disease. We find changes in functional connectivity in premanifest Huntington's disease that link directly to underlying patterns of white matter organization in healthy brains. Specifically, brain areas with strong structural connectivity show decreases in functional connectivity in premanifest Huntington's disease relative to controls, while regions with weak structural connectivity show increases in functional connectivity. Furthermore, we identify a pattern of dissociation in the strongest functional connections between anterior and posterior brain regions such that anterior functional connectivity increases in strength in premanifest Huntington's disease, while posterior functional connectivity decreases. Our findings demonstrate that organizational principles of white matter underlie changes in functional connectivity in premanifest Huntington's disease. Furthermore, we demonstrate functional antero-posterior dissociation that is in keeping with the caudo-rostral gradient of striatal pathology in HD.

  16. White matter microstructure integrity in relation to reading proficiency☆.

    Science.gov (United States)

    Nikki Arrington, C; Kulesz, Paulina A; Juranek, Jenifer; Cirino, Paul T; Fletcher, Jack M

    2017-11-01

    Components of reading proficiency such asaccuracy, fluency, and comprehension require the successful coordination of numerous, yet distinct, cortical regions. Underlying white matter tracts allow for communication among these regions. This study utilized unique residualized tract - based spatial statistics methodology to identify the relations of white matter microstructure integrity to three components of reading proficiency in 49 school - aged children with typically developing phonological decoding skills and 27 readers with poor decoders. Results indicated that measures of white matter integrity were differentially associated with components of reading proficiency. In both typical and poor decoders, reading comprehension correlated with measures of integrity of the right uncinate fasciculus; reading comprehension was also related to the left inferior longitudinal fasciculus in poor decoders. Also in poor decoders, word reading fluency was related to the right uncinate and left inferior fronto - occipital fasciculi. Word reading was unrelated to white matter integrity in either group. These findings expand our knowledge of the association between white matter integrity and different elements of reading proficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.

    Science.gov (United States)

    Kawadler, Jamie M; Kirkham, Fenella J; Clayden, Jonathan D; Hollocks, Matthew J; Seymour, Emma L; Edey, Rosanna; Telfer, Paul; Robins, Andrew; Wilkey, Olu; Barker, Simon; Cox, Tim C S; Clark, Chris A

    2015-07-01

    Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (Psickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure. © 2015 American Heart Association, Inc.

  18. Neuromarkers of the common angiotensinogen polymorphism in healthy older adults: A comprehensive assessment of white matter integrity and cognition.

    Science.gov (United States)

    Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Zhao, Yi; Luo, Xi; Wang, Youdan; Laidlaw, David H; Cabeen, Ryan P; Conturo, Thomas E; Tate, David F; Akbudak, Erbil; Lane, Elizabeth M; Heaps, Jodi M; Bolzenius, Jacob D; Baker, Laurie M; Cagle, Lee M; Paul, Robert H

    2016-01-01

    The common angiotensinogen (AGT) M268T polymorphism (rs699; historically referred to as M235T) has been identified as a significant risk factor for cerebrovascular pathologies, yet it is unclear if healthy older adults carrying the threonine amino acid variant have a greater risk for white matter damage in specific fiber tracts. Further, the impact of the threonine variant on cognitive function remains unknown. The present study utilized multiple indices of diffusion tensor imaging (DTI) and neuropsychological assessment to examine the integrity of specific white matter tracts and cognition between individuals with homozygous genotypes of M268T (MetMet n=27, ThrThr n=27). Differences in subcortical hyperintensity (SH) volume were also examined between groups. Results indicated that the threonine variant was associated with significantly reduced integrity in the superior longitudinal fasciculus (SLF) and the cingulate gyrus segment of the cingulum bundle (cingulum CG) compared to those with the methionine variant, and poorer cognitive performance on tests of attention/processing speed and language. Despite these associations, integrity of these tracts did not significantly mediate relationships between cognition and genetic status, and SH did not differ significantly between groups. Collectively our results suggest that the threonine variant of M268T is a significant risk factor for abnormalities in specific white matter tracts and cognitive domains in healthy older adults, independent of SH burden. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Diffusion measures indicate fight exposure-related damage to cerebral white matter in boxers and mixed martial arts fighters.

    Science.gov (United States)

    Shin, W; Mahmoud, S Y; Sakaie, K; Banks, S J; Lowe, M J; Phillips, M; Modic, M T; Bernick, C

    2014-02-01

    Traumatic brain injury is common in fighting athletes such as boxers, given the frequency of blows to the head. Because DTI is sensitive to microstructural changes in white matter, this technique is often used to investigate white matter integrity in patients with traumatic brain injury. We hypothesized that previous fight exposure would predict DTI abnormalities in fighting athletes after controlling for individual variation. A total of 74 boxers and 81 mixed martial arts fighters were included in the analysis and scanned by use of DTI. Individual information and data on fight exposures, including number of fights and knockouts, were collected. A multiple hierarchical linear regression model was used in region-of-interest analysis to test the hypothesis that fight-related exposure could predict DTI values separately in boxers and mixed martial arts fighters. Age, weight, and years of education were controlled to ensure that these factors would not account for the hypothesized effects. We found that the number of knockouts among boxers predicted increased longitudinal diffusivity and transversal diffusivity in white matter and subcortical gray matter regions, including corpus callosum, isthmus cingulate, pericalcarine, precuneus, and amygdala, leading to increased mean diffusivity and decreased fractional anisotropy in the corresponding regions. The mixed martial arts fighters had increased transversal diffusivity in the posterior cingulate. The number of fights did not predict any DTI measures in either group. These findings suggest that the history of fight exposure in a fighter population can be used to predict microstructural brain damage.

  20. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    Science.gov (United States)

    Liu, Wei

    Periventricular leukomalacia (PVL) is the predominant form of brain injury in the premature infant and the most common cause of cerebral palsy, yet no therapy currently exists for this serious human disorder. As PVL often occurs in preterm infants suffering from cerebral hypoxia/ischemia with or without prior exposure to maternal-fetal infection/inflammation, we used hypoxia/ischemia with or without lipopolysaccharide (LPS) injection, to produce clinically relevant PVL-like lesions in the white matter in postnatal day six (P6) mice. We studied the white matter pathology under different conditions, such as different durations of hypoxia and different doses of LPS, to evaluate the effects of those etiological factors on neonatal white matter injury. Distinct related pathological events were investigated at different time points during the progression of PVL. We used immunohistochemistry, histological analysis, and electron microscopy (EM) to study demylination that occurs in the white matter area, which is consistent with the pathology of human PVL. Previous studies have shown that erythropoietin (EPO) and its derivative carbamylated EPO (CEPO) are neuroprotective in various experimental models of brain injury. However, none of these studies investigated their efficacy against white matter injury using appropriate animal models of PVL. We produced unilateral or bilateral white matter injury in P6 mice using unilateral carotid ligation (UCL) followed by hypoxia (6% oxygen, 35 min) or by UCL/hypoxia plus LPS injection, respectively. We administered a single intraperitoneal (i.p.) dose of EPO or CEPO (5000 IU/kg) immediately after the insult, and found both drugs to provide significant protection against white matter injury in PVL mice compared to vehicle-treated groups. In addition, EPO and CEPO treatments attenuated neurobehavioral dysfunctions in an acute manner after PVL injury. EPO and CEPO have relatively few adverse effects, and thus may be a therapeutic agent

  1. ADAPTIVE CUTS FOR EXTRACTING SPECIFIC WHITE MATTER TRACTS.

    Science.gov (United States)

    Adluru, Nagesh; Singh, Vikas; Alexander, Andrew L

    2012-05-05

    Extracting specific white matter tracts (e.g., uncinate fasciculus) from whole brain tractography has numerous applications in studying individual differences in white matter. Typically specific tracts are extracted manually, following replicable protocols which can be prohibitively expensive for large scale studies. A tract clustering framework is a suitable computational framework but from a neuroanatomical point of view, one of the key challenges is that it is very hard to design a universal similarity function for different types of white matter tracts (e.g., projection, association, commissural tracts). In this paper, we propose an adaptive cuts framework in which, using normalized cuts motivated objective function, we adaptively learn tract-tract similarity for each specific tract class using atlas based training data. Using the learnt similarity function we train an ensemble of binary support vector machines to extract specific tracts from unlabeled whole-brain tractography sets.

  2. White matter morphometric changes uniquely predict children's reading acquisition.

    Science.gov (United States)

    Myers, Chelsea A; Vandermosten, Maaike; Farris, Emily A; Hancock, Roeland; Gimenez, Paul; Black, Jessica M; Casto, Brandi; Drahos, Miroslav; Tumber, Mandeep; Hendren, Robert L; Hulme, Charles; Hoeft, Fumiko

    2014-10-01

    This study examined whether variations in brain development between kindergarten and Grade 3 predicted individual differences in reading ability at Grade 3. Structural MRI measurements indicated that increases in the volume of two left temporo-parietal white matter clusters are unique predictors of reading outcomes above and beyond family history, socioeconomic status, and cognitive and preliteracy measures at baseline. Using diffusion MRI, we identified the left arcuate fasciculus and superior corona radiata as key fibers within the two clusters. Bias-free regression analyses using regions of interest from prior literature revealed that volume changes in temporo-parietal white matter, together with preliteracy measures, predicted 56% of the variance in reading outcomes. Our findings demonstrate the important contribution of developmental differences in areas of left dorsal white matter, often implicated in phonological processing, as a sensitive early biomarker for later reading abilities, and by extension, reading difficulties. © The Author(s) 2014.

  3. High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

    Science.gov (United States)

    2011-12-01

    Auckland: Auckland University Press; 1974. Guskiewicz K, Weaver N, Padua D, Garrett W. Epidemiology of concussion in collegiate and high school football ...Tucker A, Feuer H, et al. Concussion in professional football : epidemiological features of game injuries and review of the literature—part 3...the between-subjects fac - tor. The primary dependent measure was fractional anisotropy (FA). Data were confirmed to have a normal distribution using the

  4. High Resolution Diffusion Tensor Imaging of Cortical-Subcortical White Matter Tracts in TBI

    Science.gov (United States)

    2009-10-01

    Figure 5. Relationship between fractional anisotropy extracted from thalamic nuclei and neuropsychological testing for mild ( open circles) and...Calamante, D.L. Thomas, G.S. Pell, J. Wiersma , R. Turner, Measuring cerebral blood flow using magnetic resonance imaging techniques, Cerebral Blood Flow

  5. Minocycline protects the immature white matter against hyperoxia.

    Science.gov (United States)

    Schmitz, Thomas; Krabbe, Grietje; Weikert, Georg; Scheuer, Till; Matheus, Friederike; Wang, Yan; Mueller, Susanne; Kettenmann, Helmut; Matyash, Vitali; Bührer, Christoph; Endesfelder, Stefanie

    2014-04-01

    Poor neurological outcome in preterm infants is associated with periventricular white matter damage and hypomyelination, often caused by perinatal inflammation, hypoxia-ischemia, and hyperoxia. Minocycline has been demonstrated in animal models to protect the immature brain against inflammation and hypoxia-ischemia by microglial inhibition. Here we studied the effect of minocycline on white matter damage caused by hyperoxia. To mimic the 3- to 4-fold increase of oxygen tension caused by preterm birth, we have used the hyperoxia model in neonatal rats providing 24h exposure to 4-fold increased oxygen concentration (80% instead of 21% O2) from P6 to P7. We analyzed whether minocycline prevents activation of microglia and damage of oligodendroglial precursor cell development, and whether acute treatment of hyperoxia-exposed rats with minocycline improves long term white matter integrity. Minocycline administration during exposure to hyperoxia resulted in decreased apoptotic cell death and in improved proliferation and maturation of oligodendroglial precursor cells (OPC). Minocycline blocked changes in microglial morphology and IL-1β release induced by hyperoxia. In primary microglial cell cultures, minocycline inhibited cytokine release while in mono-cultures of OPCs, it improved survival and proliferation. Long term impairment of white matter diffusivity in MRI/DTI in P30 and P60 animals after neonatal hyperoxia was attenuated by minocycline. Minocycline protects white matter development against oxygen toxicity through direct protection of oligodendroglia and by microglial inhibition. This study moreover demonstrates long term benefits of minocycline on white matter integrity. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Astrocytes in oligodendrocyte lineage development and white matter pathology

    Directory of Open Access Journals (Sweden)

    Jiasi eLi

    2016-05-01

    Full Text Available White matter is primarily composed of myelin and myelinated axons. Structural and functional completeness of myelin is critical for the reliable and efficient transmission of information. White matter injury has been associated with the development of many demyelinating diseases. Despite a variety of scientific advances aimed at promoting re-myelination, their benefit has proven at best to be marginal. Research suggests that the failure of the re-myelination process may be the result of an unfavorable microenvironment. Astrocytes, are the most ample and diverse type of glial cells in central nervous system which display multiple functions for the cells of the oligodendrocytes lineage. As such, much attention has recently been drawn to astrocyte function in terms of white matter myelin repair. They are different in white matter from those in grey matter in specific regards to development, morphology, location, protein expression and other supportive functions. During the process of demyelination and re-myelination, the functions of astrocytes are dynamic in that they are able to change functions in accordance to different time points, triggers or reactive pathways resulting in vastly different biologic effects. They have pivotal effects on oligodendrocytes and other cell types in the oligodendrocyte lineage by serving as an energy supplier, a participant of immunological and inflammatory functions, a source of trophic factors and iron and a sustainer of homeostasis. Astrocytic impairment has been shown to be directly linked to the development of neuromyelities optica. In addition, astroctyes have also been implicated in other white matter conditions such as psychiatric disorders and neurodegenerative diseases such as Alzheimer’s disease, multiple sclerosis and amyotrophic lateral sclerosis. Inhibiting specifically detrimental signaling pathways in astrocytes while preserving their beneficial functions may be a promising approach for

  7. MRI gray and white matter measures in progressive supranuclear palsy and corticobasal syndrome.

    Science.gov (United States)

    Upadhyay, Neeraj; Suppa, Antonio; Piattella, Maria Cristina; Bologna, Matteo; Di Stasio, Flavio; Formica, Alessandra; Tona, Francesca; Colosimo, Carlo; Berardelli, Alfredo; Pantano, Patrizia

    2016-10-01

    We evaluated MRI measures of gray and white matter damages in 19 patients with progressive supranuclear palsy (PSP), 11 with corticobasal syndrome (CBS), and 14 healthy subjects (HS) to differentiate patients with PSP from those with CBS. We calculated surface-based maps of the cortical volume, cortical thickness, surface area, and voxel level maps of sub-cortical volume, and diffusion tensor imaging parameters using automated scripts implemented in FreeSurfer and FSL toolboxes. No significant differences in cortical volume loss were observed between PSP and CBS. When cortical volume was divided into cortical thickness and surface area, cortical thickness in peri-rolandic brain regions was significantly smaller in CBS than in PSP patients, whereas surface area was significantly smaller in PSP than HS. We also found widespread volume loss in sub-cortical structures in patients with PSP and CBS in comparison to HS. Both patient groups displayed diffusion tensor imaging abnormalities: compared to HS, widespread fractional anisotropy and radial diffusivity changes were observed in PSP, whereas axial and radial diffusivity changes were prominent in CBS. Mini-mental state examination positively correlated with diffusion changes in patients with PSP. In conclusion, cortical thickness, surface area, and diffusion tensor imaging parameters may be sensitive enough to help differentiate patients with PSP from those with CBS.

  8. Primary Sjögren's Syndrome White Matter Changes and Cognitive Dysfunction.

    Science.gov (United States)

    Dess, Mary; Heidenreich, Wayne F

    2016-01-01

    This case report describes a 52-year-old, female applicant for long term-care insurance with a history of an autoimmune connective tissue disease initially diagnosed as systemic lupus erythematosus (SLE). Over several years, the signs and symptoms evolved into a clear diagnosis of primary Sjögren's syndrome (PSS). The specific criteria for this diagnosis are reviewed including the symptoms, antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), abnormal salivary scintigraphy and positive Schirmer test. Symptoms of neuropathy and the possibility of a cognitive dysfunction are discussed as part of PSS. The association of white matter lesions (WML) with PSS is significant for underwriting consideration.

  9. Scalable brain network construction on white matter fibers

    Science.gov (United States)

    Chung, Moo K.; Adluru, Nagesh; Dalton, Kim M.; Alexander, Andrew L.; Davidson, Richard J.

    2011-03-01

    DTI offers a unique opportunity to characterize the structural connectivity of the human brain non-invasively by tracing white matter fiber tracts. Whole brain tractography studies routinely generate up to half million tracts per brain, which serves as edges in an extremely large 3D graph with up to half million edges. Currently there is no agreed-upon method for constructing the brain structural network graphs out of large number of white matter tracts. In this paper, we present a scalable iterative framework called the ɛ-neighbor method for building a network graph and apply it to testing abnormal connectivity in autism.

  10. Regional white matter volumes correlate with delay discounting.

    Directory of Open Access Journals (Sweden)

    Rongjun Yu

    Full Text Available A preference for immediate gratification is a central feature in addictive processes. However, the neural structures underlying reward delay tolerance are still unclear. Healthy participants (n = 121 completed a delay discounting questionnaire assessing the extent to which they prefer smaller immediate rewards to larger delayed reward after undergoing magnetic resonance imaging (MRI scanning. Whole brain voxel-based morphometric analysis shows that delay discounting severity was negatively correlated with right prefrontal subgyral white matter volume and positively correlated with white matter volume in parahippocampus/hippocampus, after whole brain correction. This study might better our understanding of the neural basis of impulsivity and addiction.

  11. Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks.

    NARCIS (Netherlands)

    Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.M.; Vrenken, H.

    2014-01-01

    Background In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion-filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim To determine whether 2DT2 lesion masks

  12. Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Jørgensen, K N; Nerland, S; Norbom, L B; Doan, N T; Nesvåg, R; Mørch-Johnsen, L; Haukvik, U K; Melle, I; Andreassen, O A; Westlye, L T; Agartz, I

    2016-07-01

    Schizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface. MRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0-60% into the cortical ribbon) and average white-matter intensity (sampled 0-1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex. Patients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose. Increased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

  13. White matter alterations in temporal lobe epilepsy

    Science.gov (United States)

    Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

    2011-03-01

    In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

  14. Sorting out the clinical consequences of ischemic lesions in brain aging: a clinicopathological approach.

    Science.gov (United States)

    Gold, Gabriel; Kovari, Enikö; Hof, Patrick R; Bouras, Constantin; Giannakopoulos, Panteleimon

    2007-06-15

    Vascular lesions are particularly common in the aged brain. However, it is still unclear whether all such lesions affect cognition. To better explore relationships between specific characteristics of vascular lesions (type, size and location) and cognitive status. We performed a review of currently available neuroimaging and post-mortem studies taking into account several recent clinicopathological reports in elderly individuals with varying levels of cognitive impairment. New data reveals the significant impact of cortical microinfarcts on intellectual function, in contrast to focal cortical and white matter gliosis which are not significantly associated with cognitive status. Structural neuroimaging studies show inconsistent data regarding the cognitive consequences of WML. Neuropathological analyses reveal that both periventricular and subcortical demyelination are associated with cognitive status in the absence of macrovascular pathology. When lacunes are present, these microvascular lesions have no independent effect on intellectual impairment. The relationship between lacunes and cognition is highly dependent on localization. Basal ganglia and thalamic lacunes correlate with cognitive decline but not lacunes in the frontal, temporal and parietal deep white matter. Recent studies suggest that some cases of dementia might be misclassified: 1. Cases with typical Alzheimer course and moderate lacunes in subcortical white matter should probably be considered pure Alzheimer's disease. 2. The presence of microscopic infarcts can markedly impact cognition but is not detectable by currently available neuroimaging techniques and the vascular component of such mixed cases may go undiagnosed. The development of urgently needed new criteria for vascular dementia should take into account the relative contribution of various types of vascular lesions that can impact cognitive function.

  15. Supervised learning technique for the automated identification of white matter hyperintensities in traumatic brain injury.

    Science.gov (United States)

    Stone, James R; Wilde, Elisabeth A; Taylor, Brian A; Tate, David F; Levin, Harvey; Bigler, Erin D; Scheibel, Randall S; Newsome, Mary R; Mayer, Andrew R; Abildskov, Tracy; Black, Garrett M; Lennon, Michael J; York, Gerald E; Agarwal, Rajan; DeVillasante, Jorge; Ritter, John L; Walker, Peter B; Ahlers, Stephen T; Tustison, Nicholas J

    2016-01-01

    White matter hyperintensities (WMHs) are foci of abnormal signal intensity in white matter regions seen with magnetic resonance imaging (MRI). WMHs are associated with normal ageing and have shown prognostic value in neurological conditions such as traumatic brain injury (TBI). The impracticality of manually quantifying these lesions limits their clinical utility and motivates the utilization of machine learning techniques for automated segmentation workflows. This study develops a concatenated random forest framework with image features for segmenting WMHs in a TBI cohort. The framework is built upon the Advanced Normalization Tools (ANTs) and ANTsR toolkits. MR (3D FLAIR, T2- and T1-weighted) images from 24 service members and veterans scanned in the Chronic Effects of Neurotrauma Consortium's (CENC) observational study were acquired. Manual annotations were employed for both training and evaluation using a leave-one-out strategy. Performance measures include sensitivity, positive predictive value, [Formula: see text] score and relative volume difference. Final average results were: sensitivity = 0.68 ± 0.38, positive predictive value = 0.51 ± 0.40, [Formula: see text] = 0.52 ± 0.36, relative volume difference = 43 ± 26%. In addition, three lesion size ranges are selected to illustrate the variation in performance with lesion size. Paired with correlative outcome data, supervised learning methods may allow for identification of imaging features predictive of diagnosis and prognosis in individual TBI patients.

  16. Axonal disruption in white matter underlying cortical sulcus tau pathology in chronic traumatic encephalopathy.

    Science.gov (United States)

    Holleran, Laurena; Kim, Joong Hee; Gangolli, Mihika; Stein, Thor; Alvarez, Victor; McKee, Ann; Brody, David L

    2017-03-01

    Chronic traumatic encephalopathy (CTE) is a progressive degenerative disorder associated with repetitive traumatic brain injury. One of the primary defining neuropathological lesions in CTE, based on the first consensus conference, is the accumulation of hyperphosphorylated tau in gray matter sulcal depths. Post-mortem CTE studies have also reported myelin loss, axonal injury and white matter degeneration. Currently, the diagnosis of CTE is restricted to post-mortem neuropathological analysis. We hypothesized that high spatial resolution advanced diffusion MRI might be useful for detecting white matter microstructural changes directly adjacent to gray matter tau pathology. To test this hypothesis, formalin-fixed post-mortem tissue blocks from the superior frontal cortex of ten individuals with an established diagnosis of CTE were obtained from the Veterans Affairs-Boston University-Concussion Legacy Foundation brain bank. Advanced diffusion MRI data was acquired using an 11.74 T MRI scanner at Washington University with 250 × 250 × 500 µm3 spatial resolution. Diffusion tensor imaging, diffusion kurtosis imaging and generalized q-sampling imaging analyses were performed in a blinded fashion. Following MRI acquisition, tissue sections were tested for phosphorylated tau immunoreactivity in gray matter sulcal depths. Axonal disruption in underlying white matter was assessed using two-dimensional Fourier transform analysis of myelin black gold staining. A robust image co-registration method was applied to accurately quantify the relationship between diffusion MRI parameters and histopathology. We found that white matter underlying sulci with high levels of tau pathology had substantially impaired myelin black gold Fourier transform power coherence, indicating axonal microstructural disruption (r = -0.55, p = 0.0015). Using diffusion tensor MRI, we found that fractional anisotropy (FA) was modestly (r = 0.53) but significantly (p = 0.0012) correlated with

  17. Efficacy of the transtemporal approach with awake brain mapping to reach the dominant posteromedial temporal lesions.

    Science.gov (United States)

    Iijima, Kentaro; Motomura, Kazuya; Chalise, Lushun; Hirano, Masaki; Natsume, Atsushi; Wakabayashi, Toshihiko

    2017-01-01

    Surgeries for lesions in the dominant hippocampal and parahippocampal gyrus involving the posteromedial temporal regions are challenging to perform because they are located close to Wernicke's area; white matter fibers related with language; the optic radiations; and critical neurovascular structures. We performed a transtemporal approach with awake functional mapping for lesions affecting the dominant posteromedial temporal regions. The aim of this study was to assess the feasibility, safety, and efficacy of awake craniotomy for these lesions. We retrospectively reviewed four consecutive patients with tumors or cavernous angiomas located in the left hippocampal and parahippocampal gyrus, which further extended to the posteromedial temporal regions, who underwent awake surgery between December 2014 and January 2016. Four patients with lesions associated with the left hippocampal and parahippocampal gyrus, including the posteromedial temporal area, who underwent awake surgery were registered in the study. In all four patients, cortical and subcortical eloquent areas were identified via direct electrical stimulation. This allowed determination of the optimal surgical route to the angioma or tumor, even in the language-dominant hippocampal and parahippocampal gyrus. In particular, this approach enabled access to the upper part of posteromedial temporal lesions, while protecting the subcortical language-related fibers, such as the superior longitudinal fasciculus. This study revealed that awake brain mapping can enable the safe resection of dominant posteromedial temporal lesions, while protecting cortical and subcortical eloquent areas. Furthermore, our experience with four patients demonstrates the feasibility, safety, and efficacy of awake surgery for these lesions.

  18. White matter tract alterations in Parkinson's disease patients with punding.

    Science.gov (United States)

    Canu, Elisa; Agosta, Federica; Markovic, Vladana; Petrovic, Igor; Stankovic, Iva; Imperiale, Francesca; Stojkovic, Tanja; Copetti, Massimiliano; Kostic, Vladimir S; Filippi, Massimo

    2017-10-01

    To assess brain white matter tract alterations in patients with Parkinson's disease and punding (PD-punding) compared with controls and PD cases without any impulsive-compulsive behaviour. Forty-nine PD patients (21 PD-punding and 28 PD with no impulsive-compulsive behaviours) and 28 controls were consecutively recruited. Clinical, cognitive and psychopathological evaluations were performed. Diffusion tensor MRI metrics of the main white matter tracts were assessed using a tractography approach. Compared with controls, both PD groups showed white matter microstructural alterations of the left pedunculopontine tract and splenium of the corpus callosum. PD-punding patients showed a further damage to the right pedunculopontine tract and uncinate fasciculus, genu of the corpus callosum, and left parahippocampal tract relative to controls. When adjusting for depression and/or apathy severity, a greater damage of the genu of the corpus callosum and the left pedunculopontine tract was found in PD-punding compared with patients with no impulsive-compulsive behaviours. PD-punding is associated with a disconnection between midbrain, limbic and white matter tracts projecting to the frontal cortices. These alterations are at least partially independent of their psychopathological changes. Diffusion tensor MRI is a powerful tool for understanding the neural substrates underlying punding in PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. White matter abnormalities in adolescents with major depressive disorder.

    Science.gov (United States)

    Bessette, Katie L; Nave, Andrea M; Caprihan, Arvind; Stevens, Michael C

    2014-12-01

    The purpose of this study was to identify areas of abnormal white matter microstructure in adolescents with Major Depressive Disorder (MDD) using diffusion tensor imaging (DTI). Fractional anisotropy (FA) values representing preferential diffusivity along major tracts were examined using tract-based spatial statistics across the whole brain in adolescents ages 13-19 with MDD (n = 31) compared with demographically-matched healthy controls (n = 31). We not only examined frontal lobe tracts that have been most frequently identified as abnormal in previous DTI studies of older depressed patients, but also tested for FA group differences across the whole brain to determine if adolescent depression was related to any other regional white matter abnormality. MDD-diagnosed adolescents had significantly lower FA in many regions concentrated predominantly in the frontal lobe. There also was strong evidence for lower FA in bilateral anterior/posterior limbs of the internal capsules, as well as tracts through the midbrain, left external capsule, right thalamic radiation and left inferior longitudinal fasciculus. Consistent with previous findings in depressed young and elderly adults, the current study found evidence for abnormal microstructure in white matter connections of the frontal lobe in MDD adolescents. There also was strong evidence for FA abnormalities in corpus callosum genu, internal and external capsule tracts, thalamus and midbrain, notable for both the relative magnitude of these effects and absence from most previous white matter studies of depression. These abnormalities might represent important markers of early life-onset depression.

  20. White Matter Volume Predicts Language Development in Congenital Heart Disease.

    Science.gov (United States)

    Rollins, Caitlin K; Asaro, Lisa A; Akhondi-Asl, Alireza; Kussman, Barry D; Rivkin, Michael J; Bellinger, David C; Warfield, Simon K; Wypij, David; Newburger, Jane W; Soul, Janet S

    2017-02-01

    To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. ClinicalTrials.gov: NCT00006183. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. White matter microstructure correlates of mathematical giftedness and intelligence quotient.

    Science.gov (United States)

    Navas-Sánchez, Francisco J; Alemán-Gómez, Yasser; Sánchez-Gonzalez, Javier; Guzmán-De-Villoria, Juan A; Franco, Carolina; Robles, Olalla; Arango, Celso; Desco, Manuel

    2014-06-01

    Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking. We used diffusion tensor imaging to assess white matter microstructure in neuroanatomical connectivity. The processing included voxel-wise and region of interest-based analyses of the fractional anisotropy (FA), a parameter which is purportedly related to white matter microstructure. In a whole-sample analysis, IQ showed a significant positive correlation with FA, mainly in the corpus callosum, supporting the idea that efficient information transfer between hemispheres is crucial for higher intellectual capabilities. In addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white matter tracts connecting frontal lobes with basal ganglia and parietal regions. The enhanced anatomical connectivity observed in the forceps minor and splenium may underlie the greater fluid reasoning, visuospatial working memory, and creative capabilities of these children. © 2013 Wiley Periodicals, Inc.

  2. Early dynamics of white matter deficits in children developing dyslexia

    Directory of Open Access Journals (Sweden)

    Jolijn Vanderauwera

    2017-10-01

    Full Text Available Neural anomalies have been demonstrated in dyslexia. Recent studies in pre-readers at risk for dyslexia and in pre-readers developing poor reading suggest that these anomalies might be a cause of their reading impairment. Our study goes one step further by exploring the neurodevelopmental trajectory of white matter anomalies in pre-readers with and without a familial risk for dyslexia (n = 61 of whom a strictly selected sample develops dyslexia later on (n = 15. We collected longitudinal diffusion MRI and behavioural data until grade 3. The results provide evidence that children with dyslexia exhibit pre-reading white matter anomalies in left and right long segment of the arcuate fasciculus (AF, with predictive power of the left segment above traditional cognitive measures and familial risk. Whereas white matter differences in the left AF seem most strongly related to the development of dyslexia, differences in the left IFOF and in the right AF seem driven by both familial risk and later reading ability. Moreover, differences in the left AF appeared to be dynamic. This study supports and expands recent insights into the neural basis of dyslexia, pointing towards pre-reading anomalies related to dyslexia, as well as underpinning the dynamic character of white matter.

  3. White matter hyperintensities and working memory : An explorative study

    NARCIS (Netherlands)

    van Harten, Barbera; Weinstein, Henry C.; Scheltens, Philip; Sergeant, Joseph A.; Scherder, Erik J. A.; Oosterman, J

    2008-01-01

    White matter hyperintensities (WMH) are commonly observed in elderly people and may have the most profound effect on executive functions, including working memory. Surprisingly, the Digit Span backward, a frequently employed working memory task, reveals no association with WMH. In the present study,

  4. White Matter Damage and Cognitive Impairment after Traumatic Brain Injury

    Science.gov (United States)

    Kinnunen, Kirsi Maria; Greenwood, Richard; Powell, Jane Hilary; Leech, Robert; Hawkins, Peter Charlie; Bonnelle, Valerie; Patel, Maneesh Chandrakant; Counsell, Serena Jane; Sharp, David James

    2011-01-01

    White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury…

  5. Anomalous White Matter Morphology in Adults Who Stutter

    Science.gov (United States)

    Cieslak, Matthew; Ingham, Rojer J.; Ingham, Janis C.; Grafton, Scott T.

    2015-01-01

    Aims: Developmental stuttering is now generally considered to arise from genetic determinants interacting with neurologic function. Changes within speech-motor white matter (WM) connections may also be implicated. These connections can now be studied in great detail by high-angular-resolution diffusion magnetic resonance imaging. Therefore,…

  6. A neuropathological, stereo-EEG, and MRI study of subcortical band heterotopia.

    Science.gov (United States)

    Mai, R; Tassi, L; Cossu, M; Francione, S; Lo Russo, G; Garbelli, R; Ferrario, A; Galli, C; Taroni, F; Citterio, A; Spreafico, R

    2003-06-10

    The authors performed an MRI, stereo-EEG, and pathology study on a woman with subcortical band heterotopia and partial epilepsy. Clinical manifestations of seizures always started when ictal discharges were present in outer and heterotopic cortices. Simultaneous activation of both cortices and presence of differentiated neurons in the white matter and the heterotopia strongly suggest that the cortices were anatomically and functionally interconnected.

  7. Double inversion recovery magnetic resonance imaging of subcortical band heterotopia: a report of 2 cases.

    Science.gov (United States)

    Zhang, Quan; Zhang, Yunting; Zhang, Jing; Li, Qiong

    2011-01-01

    We report 2 cases of subcortical band heterotopia (SBH) with emphasis on double inversion recovery (DIR) magnetic resonance imaging (MRI). The heterotopic gray matter demonstrated homogeneous high signal intensity and the delineation between the SBH and white matter was distinctly depicted on DIR MRI. Double inversion recovery is a useful adjunct to conventional MRI for the diagnosis of SBH.

  8. Autopsy case of acute multiple sclerosis with multifocal low density areas in the cerebral white matter on CT scans

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    Kamikura, Isao; Mizutani, Tomohiko; Sakamaki, Shuji; Takasu, Toshiaki; Kawamura, Toshiaki

    1988-01-01

    A 34-year-old woman presented with urination difficulty and consciousness disturbance, followed by persistent neurologic findings, such as semicomatose mental status and bilateral optic neuritis, and monophasic clinical course. Cranial CT showed multifocal low density areas in cerebral white matter. The patient was clinically diagnosed as having acute disseminated encephalomyelitis. She died of sepsis four months later. Autopsy revealed multifocal large demyelinating lesions confined to the cerebral white matter, shown as low density areas on CT scans, and demyelinating plaques scattered in the optic nerves and chiasm, and cerebral peduncle. The final diagnosis was acute multiple sclerosis. The CT appearance of multifocal low density areas was most likely due to demyelinating lesions causing edema and tissue necrosis. (Namekawa, K.).

  9. White matter development and early cognition in babies and toddlers.

    Science.gov (United States)

    O'Muircheartaigh, Jonathan; Dean, Douglas C; Ginestet, Cedric E; Walker, Lindsay; Waskiewicz, Nicole; Lehman, Katie; Dirks, Holly; Piryatinsky, Irene; Deoni, Sean C L

    2014-09-01

    The normal myelination of neuronal axons is essential to neurodevelopment, allowing fast inter-neuronal communication. The most dynamic period of myelination occurs in the first few years of life, in concert with a dramatic increase in cognitive abilities. How these processes relate, however, is still unclear. Here we aimed to use a data-driven technique to parcellate developing white matter into regions with consistent white matter growth trajectories and investigate how these regions related to cognitive development. In a large sample of 183 children aged 3 months to 4 years, we calculated whole brain myelin volume fraction (VFM ) maps using quantitative multicomponent relaxometry. We used spatial independent component analysis (ICA) to blindly segment these quantitative VFM images into anatomically meaningful parcels with distinct developmental trajectories. We further investigated the relationship of these trajectories with standardized cognitive scores in the same children. The resulting components represented a mix of unilateral and bilateral white matter regions (e.g., cortico-spinal tract, genu and splenium of the corpus callosum, white matter underlying the inferior frontal gyrus) as well as structured noise (misregistration, image artifact). The trajectories of these regions were associated with individual differences in cognitive abilities. Specifically, components in white matter underlying frontal and temporal cortices showed significant relationships to expressive and receptive language abilities. Many of these relationships had a significant interaction with age, with VFM becoming more strongly associated with language skills with age. These data provide evidence for a changing coupling between developing myelin and cognitive development. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  10. Clinical presentation and outcome of geriatric depression in subcortical ischemic vascular disease.

    Science.gov (United States)

    Bella, R; Pennisi, G; Cantone, M; Palermo, F; Pennisi, M; Lanza, G; Zappia, M; Paolucci, S

    2010-01-01

    Vascular damage of frontal-subcortical circuits involved in mood regulation and cognition might be the main contributor to the pathogenesis of late-life depression, and it is linked to poor response to treatment. To investigate the relationship between executive dysfunction and outcome of depressive symptoms among elderly patients with subcortical ischemic vascular disease. Ninety-two elderly patients with white matter lesions (WMLs) or lacunar infarcts (LAs) on brain MRI and depressive symptomatology were consecutively recruited. Depression was rated with the Hamilton Depression Rating Scale (HDRS). Evaluation of executive functions by means of the Stroop color-word test was performed at entry of the study, and WMLs were categorized into mild, moderate or severe. Mood was reevaluated by means of HDRS after the 12th week of pharmacological treatment. Psychomotor retardation, difficulties at work, apathy, and lack of insight were the predominant symptoms. Fifty-six patients (62.8%) had a neuroradiological picture of WMLs, while the remaining 33 (37.1%) had LAs. Executive dysfunctions significantly and independently predict poor outcome of depressive symptoms. Patients with the severest WMLs showed not only a greater executive dysfunction, but also a minor response to antidepressant treatment. This study supports the vascular depression hypothesis. WMLs are of crucial clinical relevance as they are linked with cognitive symptoms and poor antidepressant outcome. 2009 S. Karger AG, Basel.

  11. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder.

    Science.gov (United States)

    Blackmon, Karen; Ben-Avi, Emma; Wang, Xiuyuan; Pardoe, Heath R; Di Martino, Adriana; Halgren, Eric; Devinsky, Orrin; Thesen, Thomas; Kuzniecky, Ruben

    2016-01-01

    Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD) than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC). Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE) open-access database, were analyzed to compare groups on (1) blinded review of high-resolution T1-weighted research sequences; and (2) quantitative measurement of white matter hypointensity (WMH) volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC), also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.

  12. Longitudinal diffusion changes in prodromal and early HD: Evidence of white-matter tract deterioration.

    Science.gov (United States)

    Shaffer, Joseph J; Ghayoor, Ali; Long, Jeffrey D; Kim, Regina Eun-Young; Lourens, Spencer; O'Donnell, Lauren J; Westin, Carl-Fredrik; Rathi, Yogesh; Magnotta, Vincent; Paulsen, Jane S; Johnson, Hans J

    2017-03-01

    Huntington's disease (HD) is a genetic neurodegenerative disorder that primarily affects striatal neurons. Striatal volume loss is present years before clinical diagnosis; however, white matter degradation may also occur prior to diagnosis. Diffusion-weighted imaging (DWI) can measure microstructural changes associated with degeneration that precede macrostructural changes. DWI derived measures enhance understanding of degeneration in prodromal HD (pre-HD). As part of the PREDICT-HD study, N = 191 pre-HD individuals and 70 healthy controls underwent two or more (baseline and 1-5 year follow-up) DWI, with n = 649 total sessions. Images were processed using cutting-edge DWI analysis methods for large multicenter studies. Diffusion tensor imaging (DTI) metrics were computed in selected tracts connecting the primary motor, primary somato-sensory, and premotor areas of the cortex with the subcortical caudate and putamen. Pre-HD participants were divided into three CAG-Age Product (CAP) score groups reflecting clinical diagnosis probability (low, medium, or high probabilities). Baseline and longitudinal group differences were examined using linear mixed models. Cross-sectional and longitudinal differences in DTI measures were present in all three CAP groups compared with controls. The high CAP group was most affected. This is the largest longitudinal DWI study of pre-HD to date. Findings showed DTI differences, consistent with white matter degeneration, were present up to a decade before predicted HD diagnosis. Our findings indicate a unique role for disrupted connectivity between the premotor area and the putamen, which may be closely tied to the onset of motor symptoms in HD. Hum Brain Mapp 38:1460-1477, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Periventricular white matter abnormalities and restricted repetitive behavior in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Karen Blackmon

    2016-01-01

    Full Text Available Malformations of cortical development are found at higher rates in autism spectrum disorder (ASD than in healthy controls on postmortem neuropathological evaluation but are more variably observed on visual review of in-vivo MRI brain scans. This may be due to the visually elusive nature of many malformations on MRI. Here, we utilize a quantitative approach to determine whether a volumetric measure of heterotopic gray matter in the white matter is elevated in people with ASD, relative to typically developing controls (TDC. Data from a primary sample of 48 children/young adults with ASD and 48 age-, and gender-matched TDCs, selected from the Autism Brain Imaging Data Exchange (ABIDE open-access database, were analyzed to compare groups on (1 blinded review of high-resolution T1-weighted research sequences; and (2 quantitative measurement of white matter hypointensity (WMH volume calculated from the same T1-weighted scans. Groupwise WMH volume comparisons were repeated in an independent, multi-site sample (80 ASD/80 TDC, also selected from ABIDE. Visual review resulted in equivalent proportions of imaging abnormalities in the ASD and TDC group. However, quantitative analysis revealed elevated periventricular and deep subcortical WMH volumes in ASD. This finding was replicated in the independent, multi-site sample. Periventricular WMH volume was not associated with age but was associated with greater restricted repetitive behaviors on both parent-reported and clinician-rated assessment inventories. Thus, findings demonstrate that periventricular WMH volume is elevated in ASD and associated with a higher degree of repetitive behaviors and restricted interests. Although the etiology of focal WMH clusters is unknown, the absence of age effects suggests that they may reflect a static anomaly.

  14. Statistical machine learning to identify traumatic brain injury (TBI) from structural disconnections of white matter networks.

    Science.gov (United States)

    Mitra, Jhimli; Shen, Kai-Kai; Ghose, Soumya; Bourgeat, Pierrick; Fripp, Jurgen; Salvado, Olivier; Pannek, Kerstin; Taylor, D Jamie; Mathias, Jane L; Rose, Stephen

    2016-04-01

    Identifying diffuse axonal injury (DAI) in patients with traumatic brain injury (TBI) presenting with normal appearing radiological MRI presents a significant challenge. Neuroimaging methods such as diffusion MRI and probabilistic tractography, which probe the connectivity of neural networks, show significant promise. We present a machine learning approach to classify TBI participants primarily with mild traumatic brain injury (mTBI) based on altered structural connectivity patterns derived through the network based statistical analysis of structural connectomes generated from TBI and age-matched control groups. In this approach, higher order diffusion models were used to map white matter connections between 116 cortical and subcortical regions. Tracts between these regions were generated using probabilistic tracking and mean fractional anisotropy (FA) measures along these connections were encoded in the connectivity matrices. Network-based statistical analysis of the connectivity matrices was performed to identify the network differences between a representative subset of the two groups. The affected network connections provided the feature vectors for principal component analysis and subsequent classification by random forest. The validity of the approach was tested using data acquired from a total of 179 TBI patients and 146 controls participants. The analysis revealed altered connectivity within a number of intra- and inter-hemispheric white matter pathways associated with DAI, in consensus with existing literature. A mean classification accuracy of 68.16%±1.81% and mean sensitivity of 80.0%±2.36% were achieved in correctly classifying the TBI patients evaluated on the subset of the participants that was not used for the statistical analysis, in a 10-fold cross-validation framework. These results highlight the potential for statistical machine learning approaches applied to structural connectomes to identify patients with diffusive axonal injury. Copyright

  15. Relationship between progression of brain white matter changes and late-life depression

    DEFF Research Database (Denmark)

    Firbank, Michael J; Teodorczuk, Andrew; van der Flier, Wiesje M

    2012-01-01

    Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.......Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear....

  16. The effects of white matter hyperintensities and amyloid deposition on Alzheimer dementia

    Directory of Open Access Journals (Sweden)

    Brian A. Gordon

    2015-01-01

    Conclusions: The amount of amyloid deposition and white matter damage independently predicts cognitive impairment. This suggests a diagnostic utility of qualitative white matter scales in addition to measuring amyloid levels.

  17. A general factor of brain white matter integrity predicts information processing speed in healthy older people

    National Research Council Canada - National Science Library

    Penke, Lars; Muñoz Maniega, Susana; Murray, Catherine; Gow, Alan J; Hernández, Maria C Valdés; Clayden, Jonathan D; Starr, John M; Wardlaw, Joanna M; Bastin, Mark E; Deary, Ian J

    2010-01-01

    Human white matter integrity has been related to information processing speed, but it is unknown whether impaired integrity results from localized processes or is a general property shared across white matter tracts...

  18. Strength of Temporal White Matter Pathways Predicts Semantic Learning.

    Science.gov (United States)

    Ripollés, Pablo; Biel, Davina; Peñaloza, Claudia; Kaufmann, Jörn; Marco-Pallarés, Josep; Noesselt, Toemme; Rodríguez-Fornells, Antoni

    2017-11-15

    Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy. SIGNIFICANCE STATEMENT The language-processing network is cortically (i.e., gray matter) well defined. However, the role of the

  19. White matter structure changes as adults learn a second language.

    Science.gov (United States)

    Schlegel, Alexander A; Rudelson, Justin J; Tse, Peter U

    2012-08-01

    Traditional models hold that the plastic reorganization of brain structures occurs mainly during childhood and adolescence, leaving adults with limited means to learn new knowledge and skills. Research within the last decade has begun to overturn this belief, documenting changes in the brain's gray and white matter as healthy adults learn simple motor and cognitive skills [Lövdén, M., Bodammer, N. C., Kühn, S., Kaufmann, J., Schütze, H., Tempelmann, C., et al. Experience-dependent plasticity of white-matter microstructure extends into old age. Neuropsychologia, 48, 3878-3883, 2010; Taubert, M., Draganski, B., Anwander, A., Müller, K., Horstmann, A., Villringer, A., et al. Dynamic properties of human brain structure: Learning-related changes in cortical areas and associated fiber connections. The Journal of Neuroscience, 30, 11670-11677, 2010; Scholz, J., Klein, M. C., Behrens, T. E. J., & Johansen-Berg, H. Training induces changes in white-matter architecture. Nature Neuroscience, 12, 1370-1371, 2009; Draganski, B., Gaser, C., Busch, V., Schuirer, G., Bogdahn, U., & May, A. Changes in grey matter induced by training. Nature, 427, 311-312, 2004]. Although the significance of these changes is not fully understood, they reveal a brain that remains plastic well beyond early developmental periods. Here we investigate the role of adult structural plasticity in the complex, long-term learning process of foreign language acquisition. We collected monthly diffusion tensor imaging scans of 11 English speakers who took a 9-month intensive course in written and spoken Modern Standard Chinese as well as from 16 control participants who did not study a language. We show that white matter reorganizes progressively across multiple sites as adults study a new language. Language learners exhibited progressive changes in white matter tracts associated with traditional left hemisphere language areas and their right hemisphere analogs. Surprisingly, the most significant changes

  20. High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage

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    David Ley

    2016-08-01

    Full Text Available Severe cerebral intraventricular hemorrhage (IVH in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH.Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 hours following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e. not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH.

  1. Considerations for the optimization of induced white matter injury preclinical models

    OpenAIRE

    Abdullah Shafique Ahmad; Irawan eSatriotomo; Jawad eFazal; Stephen eNadeau; Sylvain eDoré

    2015-01-01

    The white matter injury in relation to acute neurologic conditions, especially stroke, has remained obscure until recently. Current advances in the imaging technologies in the field of stroke have confirmed that white matter injury plays an important role in the prognosis of stroke and suggest that white matter protection is essential for functional recovery and post-stroke rehabilitation. However, due to the lack of a reproducible animal model of white matter injury, the pathophysiology and ...

  2. Lower Orbital Frontal White Matter Integrity in Adolescents with Bipolar I Disorder

    Science.gov (United States)

    Kafantaris, Vivian; Kingsley, Peter; Ardekani, Babak; Saito, Ema; Lencz, Todd; Lim, Kelvin; Szeszko, Philip

    2009-01-01

    Patients with bipolar I disorder demonstrated white matter abnormalities in white matter regions as seen through the use of diffusion tensor imaging. The findings suggest that white matter abnormalities in pediatric bipolar disorder may be useful in constructing neurobiological models of the disorder.

  3. File list: His.Neu.20.AllAg.White_Matter [Chip-atlas[Archive

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  7. APPLICATION OF STEREOLOGICAL METHODS TO STUDY THE WHITE MATTER AND MYELINATED FIBERS THEREIN OF RAT BRAIN

    Directory of Open Access Journals (Sweden)

    Shu Yang

    2011-05-01

    Full Text Available An efficient and unbiased stereological method was applied to estimate the white matter volume, the total volume, total length and mean diameter of the myelinated fibers in the white matter and the total volume of the myelin sheaths in the white matter of rat brain. The white matter volume was obtained with the Cavalieri principle. Four tissue blocks were sampled from the entire white matter in a uniform random fashion. The length density of the myelinated fibers in the white matter was obtained from the isotropic, uniform, random sections ensured by the isector. The volume density of the myelinated fibers in the white matter was estimated by point counting. The total length and the total volume of the myelinated fibers in the white matter were estimated by multiplying the white matter volume and the length density and the volume density of the myelinated fibers in the white matter, respectively. The size of nerve fibers was derived by measuring the profile diameter perpendicular to its longest axis. The results were satisfactory in the sense that the sampling variance introduced by the stereological estimation procedure was a minor fraction of the observed variance. The comparison of the white matter and the myelinated fibers in the white matter between rat brain and human brain was also made in the present study.

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  12. Microstructural white matter changes in primary torsion dystonia.

    Science.gov (United States)

    Carbon, Maren; Kingsley, Peter B; Tang, Chengke; Bressman, Susan; Eidelberg, David

    2008-01-30

    Primary torsion dystonia (PTD) has been conceptualized as a disorder of the basal ganglia. However, recent data suggest a widespread pathology involving motor control pathways. In this report, we explored whether PTD is associated with abnormal anatomical connectivity within motor control pathways. We used diffusion tensor magnetic resonance imaging (DT-MRI) to assess the microstructure of white matter. We found that fractional anisotropy, a measure of axonal integrity and coherence, was significantly reduced in PTD patients in the pontine brainstem in the vicinity of the left superior cerebellar peduncle and bilaterally in the white matter of the sensorimotor region. Our data thus support the possibility of a disturbance in cerebello-thalamo-cortical pathways as a cause of the clinical manifestations of PTD. 2007 Movement Disorder Society

  13. The Assessment of Structural Changes in MS Plaques and Normal Appearing White Matter Using Quantitative Magnetization Transfer Imaging (MTI

    Directory of Open Access Journals (Sweden)

    Masoomeh Fooladi

    2007-12-01

    Full Text Available Introduction: Multiple sclerosis (MS is a demyelinating disease of the central nervous system (CNS, affecting mostly young people at a mean age of 30 years. Magnetic resonance imaging (MRI is one of the most specific and sensitive methods in diagnosing and detecting the evolution of multiple sclerosis disease. But it does not have the ability to differentiate between distinct histopathological heterogeneities that occur in MS lesions and brain tissue.Quantitative magnetization transfer imaging (qMTI is a relatively new MRI technique which can be used to examine the pathological processes of the brain parenchyma which occur in MS patients.This quantitative MRI technique can provide more complete information about the extent and nature of the brain tissue destruction in multiple sclerosis, which cannot be detected by conventional MRI. Material and Methods: In this study, twelve patients with relapsing-remitting MS and twelve healthy control subjects underwent conventional MR imaging including: T2-FSE, T1-SE and FLAIR sequences as well as quantitative magnetization transfer imaging. All the focal lesions were identified on T2-weighted images and were classified according to their signal hypointensity on T1-weighted scans. The white matter and MS lesions were segmented using a semi-automated system. MT ratio (MTR histogram analysis was performed for the brain white matter and the average MTR value was calculated for the classified MS lesions. Results: A significant reduction was found in MTR value of the normal appearing white matter (NAWM in patients with relapsing-remitting MS, suggesting that MS is a more diffuse disease, affecting the whole brain tissue. A wide range changes in MTR values can be observed in MS lesions. MTR reduction is correlated with the degree of lesion hypointensity on T1-weighted scans. The lower MTR values of lesions that appear progressively more hypointense on T1-weigted images reflect varying degrees of demyelination and

  14. White matter microstructure degenerates in patients with postherpetic neuralgia.

    Science.gov (United States)

    Chen, Fuxiang; Chen, Fuyong; Shang, Zhanfang; Shui, Yuan; Wu, Guorong; Liu, Chen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Kang, Dezhi; Tao, Wei; Li, Yongjie

    2017-08-24

    The central mechanisms underlying postherpetic neuralgia (PHN) pain remains unknown. The primary purpose of this study was to identify microstructural white matter changes closely related to the PHN pain by means of diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) analysis. DTI data of the brains were obtained from 8 PHN patients and 8 healthy controls (HC) that were matched in age, gender, and educational level. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were separately compared between the two groups using TBSS analysis to detect subtle microstructural changes. Partial correlation analyses were also conducted to evaluate the association between the altered DTI measures and clinical features. Average diffusion indices of white matter skeletons in the whole-brain showed no significant difference between the two groups. However, compared to the HC group, patients with PHN pain revealed reductions in localized FA and AD values in white matter underlying insula, occipital lobe, cerebellum, precentral gyrus, and many other regions, but without distinct change in regional MD and RD levels. In addition, decline of FA and AD values in patients represented significant negative correlations with PHN pain duration when the effect of VAS scores were excluded. The current study suggest that there exists altered microstructure integrity of white matter in multiple brain regions in patients with PHN, and these changes increase in size as the duration of the pain increases. These findings might provide a new insight into the mechanism of PHN pain in brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Microstructural White Matter Changes in Primary Torsion Dystonia

    OpenAIRE

    Carbon, Maren; Kingsley, Peter B.; Tang, Chengke; Bressman, Susan; Eidelberg, David

    2008-01-01

    Primary torsion dystonia (PTD) has been conceptualized as a disorder of the basal ganglia. However, recent data suggest a widespread pathology involving motor control pathways. In this report, we explored whether PTD is associated with abnormal anatomical connectivity within motor control pathways. We used diffusion tensor magnetic resonance imaging (DT-MRI) to assess the microstructure of white matter. We found that fractional anisotropy, a measure of axonal integrity and coherence, was sign...

  16. White matter correlates of sensory processing in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Jennifer R. Pryweller

    2014-01-01

    Full Text Available Autism spectrum disorder (ASD has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure.

  17. White matter correlates of sensory processing in autism spectrum disorders

    Science.gov (United States)

    Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

    2014-01-01

    Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

  18. Use of Anisotropy, 3D Segmented Atlas, and Computational Analysis to Identify Gray Matter Subcortical Lesions Common to Concussive Injury from Different Sites on the Cortex.

    Directory of Open Access Journals (Sweden)

    Praveen Kulkarni

    Full Text Available Traumatic brain injury (TBI can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA for use in a novel method of analysis to detect changes in gray matter microarchitecture. IA values from over 20,000 voxels were registered into a 3D segmented, annotated rat atlas covering 150 brain areas. Comparisons between left and right hemispheres revealed a small population of subcortical sites with altered IA values. Rostral and caudal concussions were of striking similarity in the impacted subcortical locations, particularly the central nucleus of the amygdala, laterodorsal thalamus, and hippocampal complex. Subsequent immunohistochemical analysis of these sites showed significant neuroinflammation. This study presents three significant findings that advance our understanding and evaluation of TBI: 1 the introduction of a new method to identify highly localized disturbances in discrete gray matter, subcortical brain nuclei without postmortem histology, 2 the use of this method to demonstrate that separate injuries to the rostral and caudal cortex produce the same subcortical, disturbances, and 3 the central nucleus of the amygdala, critical in the regulation of emotion, is vulnerable to concussion.

  19. Alterations in white matter pathways in Angelman syndrome.

    Science.gov (United States)

    Peters, Sarika U; Kaufmann, Walter E; Bacino, Carlos A; Anderson, Adam W; Adapa, Pavani; Chu, Zili; Yallampalli, Ragini; Traipe, Elfrides; Hunter, Jill V; Wilde, Elisabeth A

    2011-04-01

    Angelman syndrome is a neurogenetic disorder characterized by severe intellectual disability, absent speech, seizures, and outbursts of laughter. The aim of this study was to utilize diffusion tensor imaging (DTI) to examine alterations in white matter pathways in Angelman syndrome, with an emphasis on correlations with clinical severity. DTI was used to examine the arcuate fasciculus (AF), uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and the corpus callosum (CC). We enrolled 14 children aged 8 to 17 years (mean age 10y 8mo; SD 2y 7mo) with Angelman syndrome (seven male; seven female) and 13 typically developing children, aged 8 to 17 years, for comparison (five male; eight female; mean age 12y; SD 2y 9mo). Individuals with Angelman syndrome were assessed using standardized measures of development, language, and behaviour. The children with Angelman syndrome exhibited lower fractional anisotropy and increased radial diffusivity values than the comparison group for the AF, UF, ILF, and CC (p Angelman syndrome had significantly higher apparent diffusion coefficient values in the AF, CC, ILF, and the left IFOF (p Angelman syndrome suggest decreased/delayed myelination, decreased axonal density or diameter, or aberrant axonal organization. Our findings suggest a generalized white matter alteration throughout the brain in those with Angelman syndrome; however, only the alterations in temporal white matter pathways were associated with language and cognitive and social functioning. © The Authors. Journal compilation © Mac Keith Press 2010.

  20. Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.

    Science.gov (United States)

    Mayo, Chantel D; Mazerolle, Erin L; Ritchie, Lesley; Fisk, John D; Gawryluk, Jodie R

    2017-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

  1. Organising white matter in a brain without corpus callosum fibres.

    Science.gov (United States)

    Bénézit, Audrey; Hertz-Pannier, Lucie; Dehaene-Lambertz, Ghislaine; Monzalvo, Karla; Germanaud, David; Duclap, Delphine; Guevara, Pamela; Mangin, Jean-François; Poupon, Cyril; Moutard, Marie-Laure; Dubois, Jessica

    2015-02-01

    Isolated corpus callosum dysgenesis (CCD) is a congenital malformation which occurs during early development of the brain. In this study, we aimed to identify and describe its consequences beyond the lack of callosal fibres, on the morphology, microstructure and asymmetries of the main white matter bundles with diffusion imaging and fibre tractography. Seven children aged between 9 and 13 years old and seven age- and gender-matched control children were studied. First, we focused on bundles within the mesial region of the cerebral hemispheres: the corpus callosum, Probst bundles and cingulum which were selected using a conventional region-based approach. We demonstrated that the Probst bundles have a wider connectivity than the previously described rostrocaudal direction, and a microstructure rather distinct from the cingulum but relatively close to callosal remnant fibres. A sigmoid bundle was found in two partial ageneses. Second, the corticospinal tract, thalamic radiations and association bundles were extracted automatically via an atlas of adult white matter bundles to overcome bias resulting from a priori knowledge of the bundles' anatomical morphology and trajectory. Despite the lack of callosal fibres and the colpocephaly observed in CCD, all major white matter bundles were identified with a relatively normal morphology, and preserved microstructure (i.e. fractional anisotropy, mean diffusivity) and asymmetries. Consequently the bundles' organisation seems well conserved in brains with CCD. These results await further investigations with functional imaging before apprehending the cognition variability in children with isolated dysgenesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. White matter sexual dimorphism of the adult human brain

    Directory of Open Access Journals (Sweden)

    Bourisly Ali K.

    2017-05-01

    Full Text Available Sex-biased psychophysiology, behavior, brain function, and conditions are extensive, yet underlying structural brain mechanisms remain unclear. There is contradicting evidence regarding sexual dimorphism when it comes to brain structure, and there is still no consensus on whether or not there exists such a dimorphism for brain white matter. Therefore, we conducted a voxel-based morphometry (VBM analysis along with global volume analysis for white matter across sex. We analyzed 384 T1-weighted MRI brain images (192 male, 192 female to investigate any differences in white matter (WM between males and females. In the VBM analysis, we found males to have larger WM, compared to females, in occipital, temporal, insular, parietal, and frontal brain regions. In contrast, females showed only one WM region to be significantly larger than males: the right postcentral gyrus in the parietal lobe region. Although, on average, males showed larger global WM volume, we did not find any significant difference in global WM volume between males and females.

  3. Stochastic process for white matter injury detection in preterm neonates.

    Science.gov (United States)

    Cheng, Irene; Miller, Steven P; Duerden, Emma G; Sun, Kaiyu; Chau, Vann; Adams, Elysia; Poskitt, Kenneth J; Branson, Helen M; Basu, Anup

    2015-01-01

    Preterm births are rising in Canada and worldwide. As clinicians strive to identify preterm neonates at greatest risk of significant developmental or motor problems, accurate predictive tools are required. Infants at highest risk will be able to receive early developmental interventions, and will also enable clinicians to implement and evaluate new methods to improve outcomes. While severe white matter injury (WMI) is associated with adverse developmental outcome, more subtle injuries are difficult to identify and the association with later impairments remains unknown. Thus, our goal was to develop an automated method for detection and visualization of brain abnormalities in MR images acquired in very preterm born neonates. We have developed a technique to detect WMI in T1-weighted images acquired in 177 very preterm born infants (24-32 weeks gestation). Our approach uses a stochastic process that estimates the likelihood of intensity variations in nearby pixels; with small variations being more likely than large variations. We first detect the boundaries between normal and injured regions of the white matter. Following this we use a measure of pixel similarity to identify WMI regions. Our algorithm is able to detect WMI in all of the images in the ground truth dataset with some false positives in situations where the white matter region is not segmented accurately.

  4. White matter and cognition in adults who were born preterm.

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    Matthew P G Allin

    Full Text Available Individuals born very preterm (before 33 weeks of gestation, VPT are at risk of damage to developing white matter, which may affect later cognition and behaviour.We used diffusion tensor MRI (DT-MRI to assess white matter microstructure (fractional anisotropy; FA in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17-22, and 18.5 years, range 17-22 years, respectively. VPT individuals were part of a 1982-1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed.The VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only.Alterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function.

  5. The effects of puberty on white matter development in boys

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    Lara Menzies

    2015-02-01

    Full Text Available Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD and fractional anisotropy (FA in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22 and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39. Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone.

  6. White matter fractional anisotropy predicts balance performance in older adults.

    Science.gov (United States)

    Van Impe, Annouchka; Coxon, James P; Goble, Daniel J; Doumas, Mihail; Swinnen, Stephan P

    2012-09-01

    Aging is characterized by brain structural changes that may compromise motor functions. In the context of postural control, white matter integrity is crucial for the efficient transfer of visual, proprioceptive and vestibular feedback in the brain. To determine the role of age-related white matter decline as a function of the sensory feedback necessary to correct posture, we acquired diffusion weighted images in young and old subjects. A force platform was used to measure changes in body posture under conditions of compromised proprioceptive and/or visual feedback. In the young group, no significant brain structure-balance relations were found. In the elderly however, the integrity of a cluster in the frontal forceps explained 21% of the variance in postural control when proprioceptive information was compromised. Additionally, when only the vestibular system supplied reliable information, the occipital forceps was the best predictor of balance performance (42%). Age-related white matter decline may thus be predictive of balance performance in the elderly when sensory systems start to degrade. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Microstructural integrity of white matter tracts amongst older fallers: A DTI study.

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    Yoke Queen Wong

    Full Text Available This study assesses the whole brain microstructural integrity of white matter tracts (WMT among older individuals with a history of falls compared to non-fallers.85 participants (43 fallers, 42 non-fallers were evaluated with conventional MRI and diffusion tensor imaging (DTI sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.The mean diffusivity (MD and axial diffusivity (AD and to a lesser extent radial diffusivity (RD values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05 compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account.

  8. Altered topological organization of white matter structural networks in patients with neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Yaou Liu

    Full Text Available OBJECTIVE: To investigate the topological alterations of the whole-brain white-matter (WM structural networks in patients with neuromyelitis optica (NMO. METHODS: The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups. RESULTS: The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri. CONCLUSION: Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO.

  9. White matter hyperintensities on MRI in high-altitude U-2 pilots

    Science.gov (United States)

    Sherman, Paul; Profenna, Leonardo; Grogan, Patrick; Sladky, John; Brown, Anthony; Robinson, Andrew; Rowland, Laura; Hong, Elliot; Patel, Beenish; Tate, David; Kawano, Elaine S.; Fox, Peter; Kochunov, Peter

    2013-01-01

    Objective: To demonstrate that U-2 pilot occupational exposure to hypobaria leads to increased incidence of white matter hyperintensities (WMH) with a more uniform distribution throughout the brain irrespective of clinical neurologic decompression sickness history. Methods: We evaluated imaging findings in 102 U-2 pilots and 91 controls matched for age, health, and education levels. Three-dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI scanner. Whole-brain and regional WMH volume and number were compared between groups using a 2-tailed Wilcoxon rank sum test. Results: U-2 pilots demonstrated an increase in volume (394%; p = 0.004) and number (295%; p pilots compared with mainly frontal distribution in controls. Conclusion: Pilots with occupational exposure to hypobaria showed a significant increase in WMH lesion volume and number. Unlike the healthy controls with predominantly WMH in the frontal white matter, WMH in pilots were more uniformly distributed throughout the brain. This is consistent with our hypothesized pattern of damage produced by interaction between microemboli and cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or activation of innate immune response, although further studies will be necessary to clarify the pathologic mechanisms responsible. PMID:23960192

  10. Testing the white matter retrogenesis hypothesis of cognitive aging.

    Science.gov (United States)

    Brickman, Adam M; Meier, Irene B; Korgaonkar, Mayuresh S; Provenzano, Frank A; Grieve, Stuart M; Siedlecki, Karen L; Wasserman, Ben T; Williams, Leanne M; Zimmerman, Molly E

    2012-08-01

    The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior

  11. Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex.

    Science.gov (United States)

    Gelpi, Ellen; Soler Insa, Josep Ma; Parchi, Piero; Saverioni, Daniela; Yagüe, Jordi; Nos, Carlos; Martínez-Saez, Elena; Ribalta, Teresa; Ferrer, Isidre; Sanchez-Valle, Raquel

    2013-04-01

    We describe an atypical neuropatholgical phenotype of sporadic Creutzfeldt-Jakob disease (sCJD) in a 64-year-old man presenting with a 5-month history of rapidly progressive dementia, comprising behavioral disturbances, memory complaints, disorientation and language alterations. MRI showed diffuse atrophy and hyperintensities in parietal, occipital, temporal and frontal cortices and left caudate nucleus on T2-weighted and fluid-attenuated inversion recovery images. No typical EEG alterations were observed. Repeated 14-3-3 assay was positive after a first negative test. Neuropathology showed classical CJD changes with small cortical foci of large confluent vacuoles and relatively well-preserved cerebellar cortex. The most striking feature was the presence of abundant Kuru-type plaques in both cerebral cortex and subcortical white matter. Sparse Kuru-type plaques were also seen in cerebellum, although only in white matter. Immunohistochemistry showed, in addition to unicentric plaques, diffuse synaptic and patchy perivacuolar, as well as plaque-like and periaxonal pathological prion protein deposits (PrP(res) ). Western blot studies demonstrated the co-occurrence of PrP(res) types 1 and 2 in frontal cortex and a relatively weak type 2 signal in cerebellum. PRNP genotyping revealed methionine homozygosity at codon 129 and excluded mutations. This case shows a previously undescribed combination of histopathological features which preclude its classification according to the current phenotypic and molecular sCJD classification. The observation demonstrates that Kuru-type amyloid plaques mainly involving the cerebral white matter may also occur in sCJD cases with short clinical course and the co-existence of PrP(res) types 1 and 2. This case further highlights the complexity of the correlations between histopathological phenotype and PrP(res) isotype in prion diseases. © 2012 Japanese Society of Neuropathology.

  12. Dynamic corticospinal white matter connectivity changes during stroke recovery: a diffusion tensor probabilistic tractography study.

    Science.gov (United States)

    Pannek, Kerstin; Chalk, Jonathan B; Finnigan, Simon; Rose, Stephen E

    2009-03-01

    To investigate corticospinal tract connectivity changes at the cortical surface using diffusion tensor imaging (DTI) tractography during recovery from stroke. Using data from 10 stroke patients (four subcortical) and six elderly controls, we developed an automated method to quantify altered motor connectivity that involves the use of a simplified cortical surface model as a seed mask with target regions defined within the corticospinal tracts to initiate a probabilistic tractography algorithm. We found no change in volume overlap of the generated corticospinal tracts in the stroke patients compared to controls, but significant connectivity changes at the boundary of the simplified cortical surface mask, especially within the ipsilesional hemisphere of stroke patients over time. Using the cortical regions with significantly enhanced connectivity as a seed mask on the patient data, tracts that are directly associated with stroke recovery can be delineated. Measures of uncertainty in fiber orientation within these fiber tracts significantly correlated with functional outcome. The novel findings from this study highlight the usefulness of this methodology to study white matter repair/reorganization during stroke recovery. Copyright (c) 2009 Wiley-Liss, Inc.

  13. Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

    Science.gov (United States)

    Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

    2012-11-30

    Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Variable White Matter Atrophy and Intellectual Development in a Family With X-linked Creatine Transporter Deficiency Despite Genotypic Homogeneity.

    Science.gov (United States)

    Heussinger, Nicole; Saake, Marc; Mennecke, Angelika; Dörr, Helmuth-Günther; Trollmann, Regina

    2017-02-01

    The X-linked creatine transporter deficiency (CRTD) caused by an SLC6A8 mutation represents the second most common cause of X-linked intellectual disability. The clinical phenotype ranges from mild to severe intellectual disability, epilepsy, short stature, poor language skills, and autism spectrum disorders. The objective of this study was to investigate phenotypic variability in the context of genotype, cerebral creatine concentration, and volumetric analysis in a family with CRTD. The clinical phenotype and manifestations of epilepsy were assessed in a Caucasian family with CRTD. DNA sequencing and creatine metabolism analysis confirmed the diagnosis. Cerebral magnetic resonance imaging (cMRI) with voxel-based morphometry and magnetic resonance spectroscopy was performed in all family members. An SLC6A8 missense mutation (c.1169C>T; p.Pro390Leu, exon 8) was detected in four of five individuals. Both male siblings were hemizygous, the mother and the affected sister heterozygous for the mutation. Structural cMRI was normal, whereas voxel-based morphometry analysis showed reduced white matter volume below the first percentile of the reference population of 290 subjects in the more severely affected boy compared with family members and controls. Normalized creatine concentration differed significantly between the individuals (P < 0.005). There is a broad phenotypic variability in CRTD even in family members with the same mutation. Differences in mental development could be related to atrophy of the subcortical white matter. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Visual fixation in human newborns correlates with extensive white matter networks and predicts long-term neurocognitive development.

    Science.gov (United States)

    Stjerna, Susanna; Sairanen, Viljami; Gröhn, Riitta; Andersson, Sture; Metsäranta, Marjo; Lano, Aulikki; Vanhatalo, Sampsa

    2015-03-25

    Infants are well known to seek eye contact, and they prefer to fixate on developmentally meaningful objects, such as the human face. It is also known, that visual abilities are important for the developmental cascades of cognition from later infancy to childhood. It is less understood, however, whether newborn visual abilities relate to later cognitive development, and whether newborn ability for visual fixation can be assigned to early microstructural maturation. Here, we investigate relationship between newborn visual fixation (VF) and gaze behavior (GB) to performance in visuomotor and visual reasoning tasks in two cohorts with cognitive follow-up at 2 (n = 57) and 5 (n = 1410) years of age. We also analyzed brain microstructural correlates to VF (n = 45) by voxel-based analysis of fractional anisotropy (FA) in newborn diffusion tensor imaging. Our results show that newborn VF is significantly related to visual-motor performance at both 2 and 5 years, as well as to visual reasoning at 5 years of age. Moreover, good newborn VF relates to widely increased FA levels across the white matter. Comparison to motor performance indicated that early VF is preferentially related to visuocognitive development, and that early motor performance relates neither to white matter integrity nor to visuocognitive development. The present findings suggest that newborn VF is supported by brainwide subcortical networks and it represents an early building block for the developmental cascades of cognition. Copyright © 2015 the authors 0270-6474/15/354824-06$15.00/0.

  16. White matter abnormalities in the anterior temporal lobe suggest the side of the seizure foci in temporal lobe epilepsy

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    Adachi, Y.; Yagishita, A. [Tokyo Metropolitan Neurological Hospital, Department of Neuroradiology, Fuchu, Tokyo (Japan); Arai, N. [Tokyo Metropolitan Neurological Institute, Department of Clinical Neuropathology, Fuchu, Tokyo (Japan)

    2006-07-15

    White matter abnormalities in the anterior temporal lobe (WAATL) are sometimes observed on magnetic resonance (MR) images of patients with temporal lobe epilepsy (TLE). Our purpose was to determine whether WAATL could indicate if the seizure foci are ipsilateral on electroencephalograms (EEG) in TLE patients. We reviewed 112 consecutive patients with medically intractable TLE. We compared the side of seizure foci on EEG (preoperative and intraoperative) and MR images. Both loss of gray-white matter demarcation and increased signal intensity changes in the anterior white matter (positive WAATL) were observed in 54 of 112 patients (48.2%) with TLE. WAATL were present on the same side as the seizure foci on preoperative intracranial EEG with subdural electrodes (iEEG) and on intraoperative electrocorticography (ECG) in all the patients. In 47 patients, MR images showed WAATL and focal lesions that were possibly epileptogenic for TLE. In 2 of the 47 patients, the seizure foci on iEEG and ECG were contralateral to the focal lesion; in the remaining 45 patients, the seizure foci on surface EEG (sEEG) and ECG and the focal lesion were on the same side. In three patients, no focal lesions were seen but WAATL were present on the same side as the seizure foci on sEEG and ECG. In four patients, MR images showed focal lesions for which epileptogenicity was questionable, and WAATL on the same side as the seizure foci on EEG. WAATL are clinically useful because they indicate the side of the seizure foci. (orig.)

  17. Accelerated Gray and White Matter Deterioration With Age in Schizophrenia.

    Science.gov (United States)

    Cropley, Vanessa L; Klauser, Paul; Lenroot, Rhoshel K; Bruggemann, Jason; Sundram, Suresh; Bousman, Chad; Pereira, Avril; Di Biase, Maria A; Weickert, Thomas W; Weickert, Cynthia Shannon; Pantelis, Christos; Zalesky, Andrew

    2017-03-01

    Although brain changes in schizophrenia have been proposed to mirror those found with advancing age, the trajectory of gray matter and white matter changes during the disease course remains unclear. The authors sought to measure whether these changes in individuals with schizophrenia remain stable, are accelerated, or are diminished with age. Gray matter volume and fractional anisotropy were mapped in 326 individuals diagnosed with schizophrenia or schizoaffective disorder and in 197 healthy comparison subjects aged 20-65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Between-group differences in gray matter volume and fractional anisotropy were regionally localized across the lifespan using permutation testing and cluster-based inference. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35, and the rate of fractional anisotropy deterioration with age was constant and best modeled with a straight line. The slope of this line was 60% steeper in schizophrenia relative to comparison subjects, indicating a significantly faster rate of white matter deterioration with age. The rates of reduction of gray matter volume and fractional anisotropy were significantly faster in males than in females, but an interaction between sex and diagnosis was not evident. The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate.

  18. Memory binding and white matter integrity in familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Saarimäki, Heini; Bastin, Mark E; Londoño, Ana C; Pettit, Lewis; Lopera, Francisco; Della Sala, Sergio; Abrahams, Sharon

    2015-05-01

    Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to

  19. Gait and Equilibrium in Subcortical Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2011-01-01

    Full Text Available Subcortical vascular dementia is a clinical entity, widespread, even challenging to diagnose and correctly treat. Patients with this diagnosis are old, frail, often with concomitant pathologies, and therefore, with many drugs in therapy. We tried to diagnose and follow up for three years more than 600 patients. Study subjects were men and women, not bedridden, aged 68–94 years, outpatients, recruited from June, 1st 2007 to June, 1st 2010. We examined them clinically, neurologically, with specific consideration on drug therapies. Our aim has been to define gait and imbalance problem, if eventually coexistent with the pathology of white matter and/or with the worsening of the deterioration. Drug intake interference has been detected and considered.

  20. White matter hyperintensities and changes in white matter integrity in patients with Alzheimer's disease

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    Wang, Liya; Mao, Hui [Emory University School of Medicine, Department of Radiology, Atlanta, GA (United States); Emory University School of Medicine, Center for Systems Imaging, Atlanta, GA (United States); Goldstein, Felicia C.; Levey, Allan I.; Lah, James J. [Emory University School of Medicine, Department of Neurology, Atlanta, GA (United States); Meltzer, Carolyn C. [Emory University School of Medicine, Department of Radiology, Atlanta, GA (United States); Emory University School of Medicine, Center for Systems Imaging, Atlanta, GA (United States); Emory University School of Medicine, Department of Neurology, Atlanta, GA (United States); Emory University School of Medicine, Department of Psychiatry and Behavior Sciences, Atlanta, GA (United States); Holder, Chad A. [Emory University School of Medicine, Department of Radiology, Atlanta, GA (United States)

    2011-05-15

    White matter hyperintensities (WMHs) are a risk factor for Alzheimer's disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D{sub R}), and axial diffusivity (D{sub A}) were analyzed using the region of interest and tract-based spatial statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and D{sub R} were more sensitive measurements than MD and D{sub A} in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. D{sub R} may serve as an imaging marker of myelin deficits associated with AD. (orig.)

  1. Gray matter and white matter abnormalities in online game addiction

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    Weng, Chuan-Bo, E-mail: send007@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); School of Neurosurgery, Anhui Medical University, 81 Meishang Road, Hefei, Anhui Province 230032 (China); Qian, Ruo-Bing, E-mail: rehomail@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Fu, Xian-Ming, E-mail: 506537677@qq.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Lin, Bin, E-mail: 274722758@qq.com [School of Neurosurgery, Anhui Medical University, 81 Meishang Road, Hefei, Anhui Province 230032 (China); Han, Xiao-Peng, E-mail: hanxiaopeng@163.com [Department of Psychology, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Niu, Chao-Shi, E-mail: niuchaoshi@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China); Wang, Ye-Han, E-mail: wangyehan@163.com [Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, Ahui Province 230001 (China); Anhui Provincial Institute of Stereotactic Neurosurgery, 9 Lujiang Road, Hefei, Ahui Province 230001 (China)

    2013-08-15

    Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA.

  2. Brain White Matter Impairment in Patients with Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Weimin Zheng

    2017-01-01

    Full Text Available It remains unknown whether spinal cord injury (SCI could indirectly impair or reshape the white matter (WM of human brain and whether these changes are correlated with injury severity, duration, or clinical performance. We choose tract-based spatial statistics (TBSS to investigate the possible changes in whole-brain white matter integrity and their associations with clinical variables in fifteen patients with SCI. Compared with the healthy controls, the patients exhibited significant decreases in WM fractional anisotropy (FA in the left angular gyrus (AG, right cerebellum (CB, left precentral gyrus (PreCG, left lateral occipital region (LOC, left superior longitudinal fasciculus (SLF, left supramarginal gyrus (SMG, and left postcentral gyrus (PostCG (p<0.01, TFCE corrected. No significant differences were found in all diffusion indices between the complete and incomplete SCI. However, significantly negative correlation was shown between the increased radial diffusivity (RD of left AG and total motor scores (uncorrected p<0.05. Our findings provide evidence that SCI can cause not only direct degeneration but also transneuronal degeneration of brain WM, and these changes may be irrespective of the injury severity. The affection of left AG on rehabilitation therapies need to be further researched in the future.

  3. Vanishing White Matter Disease in a Spanish Population

    Directory of Open Access Journals (Sweden)

    Eulàlia Turón-Viñas

    2014-01-01

    Full Text Available Vanishing white matter (VWM leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor ( eIF2B . We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases, eIF2B3 (2 cases, and eIF2B4 (1 case. In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4 , c.314A>G in eIF2B5 , and c.877C>T in eIF2B5.

  4. White matter pathways mediate parental effects on children's reading precursors.

    Science.gov (United States)

    Vandermosten, Maaike; Cuynen, Lieselore; Vanderauwera, Jolijn; Wouters, Jan; Ghesquière, Pol

    2017-10-01

    Previous studies have shown that the link between parental and offspring's reading is mediated by the cognitive system of the offspring, yet information about the mediating role of the neurobiological system is missing. This family study includes cognitive and diffusion MRI (dMRI) data collected in 71 pre-readers as well as parental reading and environmental data. Using sequential path analyses, which take into account the interrelationships between the different components, we observed mediating effects of the neurobiological system. More specifically, fathers' reading skills predicted reading of the child by operating through a child's left ventral white matter pathway. For mothers no clear mediating role of the neural system was observed. Given that our study involves children who have not yet learned to read and that environmental measures were taken into account, the paternal effect on a child's white matter pathway is unlikely to be only driven by environmental factors. Future intergenerational studies focusing on the genetic, neurobiological and cognitive level of parents and offspring will provide more insight in the relative contribution of parental environment and genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Gray matter and white matter abnormalities in online game addiction.

    Science.gov (United States)

    Weng, Chuan-Bo; Qian, Ruo-Bing; Fu, Xian-Ming; Lin, Bin; Han, Xiao-Peng; Niu, Chao-Shi; Wang, Ye-Han

    2013-08-01

    Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Differential development of human brain white matter tracts.

    Directory of Open Access Journals (Sweden)

    Davide Imperati

    Full Text Available Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old, we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles and subdivisions within tracts (e.g., corpus callosum, internal capsule. For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted 'U-shape', with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples.

  7. A Laboratory Manual for Stepwise Cerebral White Matter Fiber Dissection.

    Science.gov (United States)

    Koutsarnakis, Christos; Liakos, Faidon; Kalyvas, Aristotelis V; Sakas, Damianos E; Stranjalis, George

    2015-08-01

    White matter fiber dissection is an important method in acquiring a thorough neuroanatomic knowledge for surgical practice. Previous studies have definitely improved our understanding of intrinsic brain anatomy and emphasized on the significance of this technique in modern neurosurgery. However, current literature lacks a complete and concentrated laboratory guide about the entire dissection procedure. Hence, our primary objective is to introduce a detailed laboratory manual for cerebral white matter dissection by highlighting consecutive dissection steps, and to stress important technical comments facilitating this complex procedure. Twenty adult, formalin-fixed cerebral hemispheres were included in the study. Ten specimens were dissected in the lateromedial and 10 in the mediolateral direction, respectively, using the fiber dissection technique and the microscope. Eleven and 8 consecutive and distinctive dissection steps are recommended for the lateromedial and mediolateral dissection procedures, respectively. Photographs highlighting various anatomic landmarks accompany every step. Technical recommendations, facilitating the dissection process, are also indicated. The fiber dissection technique, although complex and time consuming, offers a three-dimensional knowledge of intrinsic brain anatomy and architecture, thus improving both the quality of microneurosurgery and the patient's standard of care. The present anatomic study provides a thorough dissection manual to those who study brain anatomy using this technique. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Statistical estimation of white matter microstructure from conventional MRI

    Directory of Open Access Journals (Sweden)

    Leah H Suttner

    2016-01-01

    Full Text Available Diffusion tensor imaging (DTI has become the predominant modality for studying white matter integrity in multiple sclerosis (MS and other neurological disorders. Unfortunately, the use of DTI-based biomarkers in large multi-center studies is hindered by systematic biases that confound the study of disease-related changes. Furthermore, the site-to-site variability in multi-center studies is significantly higher for DTI than that for conventional MRI-based markers. In our study, we apply the Quantitative MR Estimation Employing Normalization (QuEEN model to estimate the four DTI measures: MD, FA, RD, and AD. QuEEN uses a voxel-wise generalized additive regression model to relate the normalized intensities of one or more conventional MRI modalities to a quantitative modality, such as DTI. We assess the accuracy of the models by comparing the prediction error of estimated DTI images to the scan-rescan error in subjects with two sets of scans. Across the four DTI measures, the performance of the models is not consistent: Both MD and RD estimations appear to be quite accurate, while AD estimation is less accurate than MD and RD; the accuracy of FA estimation is poor. Thus, in some cases when assessing white matter integrity, it may be sufficient to acquire conventional MRI sequences alone.

  9. Neuropsychology of subcortical dementias.

    Science.gov (United States)

    Savage, C R

    1997-12-01

    Subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychological impairment. This article describes the neurobiological and cognitive features of three prototypical subcortical dementias, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy, concentrating of traits shared by disorders. Clinical features are also discussed, especially those which differentiate subcortical dementias from cortical dementias, such as Alzheimer's disease. The cortical-subcortical nomenclature has been criticized over the years, but it continues to provide an effective means of classifying dementia profiles in clinically and theoretically useful ways.

  10. The power of hybrid / fusion imaging metrics in future PACS systems: a case study into the white matter hyperintensity prenumbra using FLAIR and diffusion MR

    Science.gov (United States)

    Tsao, Sinchai; Ma, Samantha J.; Michels, Peter A.; Gajawelli, Niharika; Law, Meng; Chui, Helena; Lepore, Natasha

    2014-04-01

    Most white matter related neurological disease exhibit a large number of White Matter Hyperintensities (WMHs) on FLAIR MRI images. However, these lesions are not well understood. At the same time, Diffusion MRI has been gaining popularity as a powerful method of characterizing White Matter (WM) integrity. This work aims to study the behavior of the diffusion signal within the WMH voxels. The goal is to develop hybrid MR metrics that leverage information from multiple MR acquisitions to solve clinical problems. In our case, we are trying to address the WMH penumbra (as defined by Maillard et al 20112) where WMH delineates a foci that is more widespread than the actual damage area presumably due to acute inflammation. Our results show that diffusion MR metrics may be able to better delineate tissue that is inflamed versus scar tissue but may be less specific to lesions than FLAIR. Therefore, a hybrid metric that encodes information from both FLAIR and Diffusion MR may yield new and novel imaging information about the progression of white matter disease progression. We hope that this work also demonstrates how future PACS systems could have image fusion capabilities that would be able to leverage information from multiple imaging series to yield new and novel imaging contrast.

  11. Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks ☆

    OpenAIRE

    Popescu, V.; Ran, N.C.G.; Barkhof, F.; Chard, D.T.; Wheeler-Kingshott, C.A.; Vrenken, H.

    2014-01-01

    Background: In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images. Aim: To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks. Methods: 2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, ...

  12. Comparison of MRI white matter changes with neuropsychologic impairment in Cockayne syndrome.

    Science.gov (United States)

    Sugita, K; Takanashi, J; Ishii, M; Niimi, H

    1992-01-01

    The neuropsychologic function and white matter changes observed on magnetic resonance imaging (MRI) in Cockayne syndrome were studied. MRI with T2-weighted sequences revealed periventricular hyperintensity and white matter hyperintensity in all 3 Cockayne syndrome patients examined; in contrast, 8 age-matched controls had no periventricular or white matter hyperintensity. MRI scans were graded according to the severity of periventricular or white matter hyperintensity using a scale applied to an elderly patient population. There was no difference in the severity of MRI white matter changes in these 3 Cockayne syndrome patients, 2 of whom had severe neuropsychologic functions and one a relatively milder one. There was no correlation between neuropsychologic impairment and MRI white matter changes.

  13. Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord.

    Science.gov (United States)

    Ek, C Joakim; Habgood, Mark D; Callaway, Jennifer K; Dennis, Ross; Dziegielewska, Katarzyna M; Johansson, Pia A; Potter, Ann; Wheaton, Benjamin; Saunders, Norman R

    2010-08-09

    Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGait analysis). We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min) lesion volumes showed very low variance (1.92+/-0.23 mm3, mean+/-SD, n=5). Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed.

  14. Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord.

    Directory of Open Access Journals (Sweden)

    C Joakim Ek

    Full Text Available Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGait analysis. We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min lesion volumes showed very low variance (1.92+/-0.23 mm3, mean+/-SD, n=5. Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed.

  15. Sentence processing and verbal working memory in a white-matter-disconnection patient.

    Science.gov (United States)

    Meyer, Lars; Cunitz, Katrin; Obleser, Jonas; Friederici, Angela D

    2014-08-01

    The Arcuate Fasciculus/Superior Longitudinal Fasciculus (AF/SLF) is the white-matter bundle that connects posterior superior temporal and inferior frontal cortex. Its causal functional role in sentence processing and verbal working memory is currently under debate. While impairments of sentence processing and verbal working memory often co-occur in patients suffering from AF/SLF damage, it is unclear whether these impairments result from shared white-matter damage to the verbal-working-memory network. The present study sought to specify the behavioral consequences of focal AF/SLF damage for sentence processing and verbal working memory, which were assessed in a single patient suffering from a cleft-like lesion spanning the deep left superior temporal gyrus, sparing most surrounding gray matter. While tractography suggests that the ventral fronto-temporal white-matter bundle is intact in this patient, the AF/SLF was not visible to tractography. In line with the hypothesis that the AF/SLF is causally involved in sentence processing, the patient׳s performance was selectively impaired on sentences that jointly involve both complex word orders and long word-storage intervals. However, the patient was unimpaired on sentences that only involved long word-storage intervals without involving complex word orders. On the contrary, the patient performed generally worse than a control group across standard verbal-working-memory tests. We conclude that the AF/SLF not only plays a causal role in sentence processing, linking regions of the left dorsal inferior frontal gyrus to the temporo-parietal region, but moreover plays a crucial role in verbal working memory, linking regions of the left ventral inferior frontal gyrus to the left temporo-parietal region. Together, the specific sentence-processing impairment and the more general verbal-working-memory impairment may imply that the AF/SLF subserves both sentence processing and verbal working memory, possibly pointing to the AF

  16. A semi-automated method for measuring thickness and white matter integrity of the corpus callosum

    Directory of Open Access Journals (Sweden)

    S Andronikou

    2012-12-01

    distance along the midline contour. The following parameters are measurable: midline CC thickness; midline FA; fibre volume for each hemisphere (represented as a left/right ratio centred on zero and mean fibre FA for each hemisphere (also represented as a left/right ratio centred on zero. Results. The tool proved successful in measuring and plotting CC midline thickness and FA, but was not sensitive for peripheral white matter lesions. Conclusions. The technique successfully determined values of CC midline thickness, FA and interhemispheric differences. Future research will determine normal values for age and compare CC thickness with peripheral white matter volume loss in large groups of patients, using the semiautomated technique.

  17. Effects of exercise on capillaries in the white matter of transgenic AD mice.

    Science.gov (United States)

    Zhang, Yi; Chao, Feng-Lei; Zhou, Chun-Ni; Jiang, Lin; Zhang, Lei; Chen, Lin-Mu; Luo, Yan-Min; Xiao, Qian; Tang, Yong

    2017-09-12

    Previous studies have shown that exercise can prevent white matter atrophy in APP/PS1 transgenic Alzheimer's disease (AD) mice. However, the mechanism of this protective effect remains unknown. To further understand this issue, we investigated the effects of exercise on the blood supply of white matter in transgenic AD mice. Six-month-old male APP/PS1 mice were randomly divided into a control group and a running group, and age-matched non-transgenic littermates were used as a wild-type control group. Mice in the running group ran on a treadmill at low intensity for four months. Then, spatial learning and memory abilities, white matter and white matter capillaries were examined in all mice. The 10-month-old AD mice exhibited deficits in cognitive function, and 4 months of exercise improved these deficits. The white matter volume and the total length, total volume and total surface area of the white matter capillaries were decreased in the 10-month-old AD mice, and 4 months of exercise dramatically delayed the changes in these parameters in the AD mice. Our results demonstrate that even low-intensity running exercise can improve spatial learning and memory abilities, delay white matter atrophy and protect white matter capillaries in early-stage AD mice. Protecting capillaries might be an important structural basis for the exercise-induced protection of the structural integrity of white matter in AD.

  18. Reduced parietooccipital white matter glutamine measured by proton magnetic resonance spectroscopy in treated graves' disease patients

    DEFF Research Database (Denmark)

    Danielsen, Else Rubæk; Elberling, T.V.; Rasmussen, Åse Krogh

    2008-01-01

    and a battery of biochemical, affective, and cognitive tests were used. RESULTS: Previously reported findings of reduced choline and myo-inositol in acute Graves' disease were confirmed and reversibility was demonstrated. Parieto-occipital white matter glutamine was and remained significantly reduced (P ....01). Acute phase parieto-occipital white matter total choline correlated significantly (r = -0.57; P glutamine (r = -0.52; P ....01) and parietooccipital white matter glutamate (r = -0.54; P glutamine in white matter, the decreasing glutamate in occipital gray matter...

  19. A multivariate pattern analysis study of the HIV-related white matter anatomical structural connections alterations

    Science.gov (United States)

    Tang, Zhenchao; Liu, Zhenyu; Li, Ruili; Cui, Xinwei; Li, Hongjun; Dong, Enqing; Tian, Jie

    2017-03-01

    It's widely known that HIV infection would cause white matter integrity impairments. Nevertheless, it is still unclear that how the white matter anatomical structural connections are affected by HIV infection. In the current study, we employed a multivariate pattern analysis to explore the HIV-related white matter connections alterations. Forty antiretroviraltherapy- naïve HIV patients and thirty healthy controls were enrolled. Firstly, an Automatic Anatomical Label (AAL) atlas based white matter structural network, a 90 × 90 FA-weighted matrix, was constructed for each subject. Then, the white matter connections deprived from the structural network were entered into a lasso-logistic regression model to perform HIV-control group classification. Using leave one out cross validation, a classification accuracy (ACC) of 90% (P=0.002) and areas under the receiver operating characteristic curve (AUC) of 0.96 was obtained by the classification model. This result indicated that the white matter anatomical structural connections contributed greatly to HIV-control group classification, providing solid evidence that the white matter connections were affected by HIV infection. Specially, 11 white matter connections were selected in the classification model, mainly crossing the regions of frontal lobe, Cingulum, Hippocampus, and Thalamus, which were reported to be damaged in previous HIV studies. This might suggest that the white matter connections adjacent to the HIV-related impaired regions were prone to be damaged.

  20. Increased white matter metabolic rates in autism spectrum disorder and schizophrenia.

    Science.gov (United States)

    Mitelman, Serge A; Buchsbaum, Monte S; Young, Derek S; Haznedar, M Mehmet; Hollander, Eric; Shihabuddin, Lina; Hazlett, Erin A; Bralet, Marie-Cecile

    2017-11-22

    Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

  1. Machine learning based compartment models with permeability for white matter microstructure imaging.

    Science.gov (United States)

    Nedjati-Gilani, Gemma L; Schneider, Torben; Hall, Matt G; Cawley, Niamh; Hill, Ioana; Ciccarelli, Olga; Drobnjak, Ivana; Wheeler-Kingshott, Claudia A M Gandini; Alexander, Daniel C

    2017-04-15

    Some microstructure parameters, such as permeability, remain elusive because mathematical models that express their relationship to the MR signal accurately are intractable. Here, we propose to use computational models learned from simulations to estimate these parameters. We demonstrate the approach in an example which estimates water residence time in brain white matter. The residence time τi of water inside axons is a potentially important biomarker for white matter pathologies of the human central nervous system, as myelin damage is hypothesised to affect axonal permeability, and thus τi. We construct a computational model using Monte Carlo simulations and machine learning (specifically here a random forest regressor) in order to learn a mapping between features derived from diffusion weighted MR signals and ground truth microstructure parameters, including τi. We test our numerical model using simulated and in vivo human brain data. Simulation results show that estimated parameters have strong correlations with the ground truth parameters (R2={0.88,0.95,0.82,0.99}) for volume fraction, residence time, axon radius and diffusivity respectively), and provide a marked improvement over the most widely used Kärger model (R2={0.75,0.60,0.11,0.99}). The trained model also estimates sensible microstructure parameters from in vivo human brain data acquired from healthy controls, matching values found in literature, and provides better reproducibility than the Kärger model on both the voxel and ROI level. Finally, we acquire data from two Multiple Sclerosis (MS) patients and compare to the values in healthy subjects. We find that in the splenium of corpus callosum (CC-S) the estimate of the residence time is 0.57±0.05s for the healthy subjects, while in the MS patient with a lesion in CC-S it is 0.33±0.12s in the normal appearing white matter (NAWM) and 0.19±0.11s in the lesion. In the corticospinal tracts (CST) the estimate of the residence time is 0.52±0.09s

  2. White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function.

    Science.gov (United States)

    Laporta-Hoyos, Olga; Pannek, Kerstin; Ballester-Plané, Júlia; Reid, Lee B; Vázquez, Élida; Delgado, Ignacio; Zubiaurre-Elorza, Leire; Macaya, Alfons; Póo, Pilar; Meléndez-Plumed, Mar; Junqué, Carme; Boyd, Roslyn; Pueyo, Roser

    2017-01-01

    Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Thirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA

  3. Plasma omega 3 PUFA and white matter mediated executive decline in older adults

    Directory of Open Access Journals (Sweden)

    Gene L. Bowman

    2013-12-01

    Full Text Available Introduction: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH mediates the putative association. Methods: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function. Results: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 μg/ml increase in plasma O3PUFA associated with 4 seconds less change in executive decline per year of aging (p = 0.02, fully adjusted model. O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model. Conclusion: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.

  4. Contrast-based fully automatic segmentation of white matter hyperintensities: method and validation.

    Directory of Open Access Journals (Sweden)

    Thomas Samaille

    Full Text Available White matter hyperintensities (WMH on T2 or FLAIR sequences have been commonly observed on MR images of elderly people. They have been associated with various disorders and have been shown to be a strong risk factor for stroke and dementia. WMH studies usually required visual evaluation of WMH load or time-consuming manual delineation. This paper introduced WHASA (White matter Hyperintensities Automated Segmentation Algorithm, a new method for automatically segmenting WMH from FLAIR and T1 images in multicentre studies. Contrary to previous approaches that were based on intensities, this method relied on contrast: non linear diffusion filtering alternated with watershed segmentation to obtain piecewise constant images with increased contrast between WMH and surroundings tissues. WMH were then selected based on subject dependant automatically computed threshold and anatomical information. WHASA was evaluated on 67 patients from two studies, acquired on six different MRI scanners and displaying a wide range of lesion load. Accuracy of the segmentation was assessed through volume and spatial agreement measures with respect to manual segmentation; an intraclass correlation coefficient (ICC of 0.96 and a mean similarity index (SI of 0.72 were obtained. WHASA was compared to four other approaches: Freesurfer and a thresholding approach as unsupervised methods; k-nearest neighbours (kNN and support vector machines (SVM as supervised ones. For these latter, influence of the training set was also investigated. WHASA clearly outperformed both unsupervised methods, while performing at least as good as supervised approaches (ICC range: 0.87-0.91 for kNN; 0.89-0.94 for SVM. Mean SI: 0.63-0.71 for kNN, 0.67-0.72 for SVM, and did not need any training set.

  5. Plasma omega-3 PUFA and white matter mediated executive decline in older adults

    Science.gov (United States)

    Bowman, Gene L.; Dodge, Hiroko H.; Mattek, Nora; Barbey, Aron K.; Silbert, Lisa C.; Shinto, Lynne; Howieson, Diane B.; Kaye, Jeffrey A.; Quinn, Joseph F.

    2013-01-01

    Introduction: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association. Methods: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function. Results: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 μg/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model. Conclusion: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation. PMID:24379780

  6. Exploring the role of white matter connectivity in cortex maturation.

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    Cecilia L Friedrichs-Maeder

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