Cerebral White Matter Regions Research Articles

Journey to the other side of the brain: asymmetry in patients with chronic mild or moderate traumatic brain injury.

Patients with chronic mild or moderate traumatic brain injury have some regions of brain atrophy (including cerebral white matter) but even more regions of abnormal brain enlargement (including other cerebral regions). Ipsilateral injury and atrophy cause the eventual development of contralateral compensatory hypertrophy. 50 patients with mild or moderate traumatic brain injury were compared to 80 normal controls (n=80) with respect to MRI brain volume asymmetry. Asymmetry-based correlations were used to test the primary hypothesis. The group of patients had multiple regions of abnormal asymmetry. The correlational analyses supported the conclusion that acute injury to ipsilateral cerebral white matter regions caused atrophy, leading eventually to abnormal enlargement of contralateral regions due to compensatory hypertrophy.

Potential interactions between pericytes and oligodendrocyte precursor cells in perivascular regions of cerebral white matter

Pericytes are embedded within basal lamina and play multiple roles in the perivascular niche in brain. Recently, oligodendrocyte precursor cells (OPCs) have also been reported to associate with cerebral endothelium. Is it possible that within this gliovascular locus, there may also exist potential spatial and functional interactions between pericytes and OPCs? Here, we demonstrated that in the perivascular region of cerebral white matter, pericytes and OPCs may attach and support each other. Immunostaining showed that pericytes and OPCs are localized in close contact with each other in mouse white matter at postnatal days 0, 60 and 240. Electron microscopic analysis confirmed that pericytes attached to OPCs via basal lamina in the perivascular region. The close proximity between these two cell types was also observed in postmortem human brains. Functional interaction between pericytes and OPCs was assessed by in vitro media transfer experiments. When OPC cultures were treated with pericyte-conditioned media, OPC number increased. Similarly, pericyte number increased when pericytes were maintained in OPC-conditioned media. Taken together, our data suggest a potential anatomical and functional interaction between pericytes and OPCs in cerebral white matter.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa.

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

Altered Brain White Matter Integrity in Temporal Lobe Epilepsy: A TBSS Study.

The aim of this study is to explore the possible changed cerebral white matter regions in patients with temporal lobe epilepsy (TLE) using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Twenty TLE patients and 22 age- and gender-matched normal controls were included in this study. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA) and mean diffusivity (MD) were performed with TBSS. TLE patients exhibited significantly reduced FA in widespread white matter regions including bilateral limbic circuit, corpus callosum, thalamus, internal/external capsule, temporooccipital connections, frontotemporal connections; increase of MD was exhibited significantly almost in the left hemisphere. A significant decrease in global FA integrity was shown in epilepsy subjects compared to healthy controls. Furthermore, it exhibited a significant positive correlation between the disease duration and MD of whole brain. TLE is associated with widespread abnormalities in cerebral white matter tracts and these changes may have important clinical consequences.

The Role of MR Imaging in Assessment of Brain Damage from Carbon Monoxide Poisoning: A Review of the Literature

The aim of this article is to review how MR imaging and associated imaging modalities provide clinicopathologic information on brain damage after carbon monoxide poisoning. Initially, many authors documented typical findings of conventional MR imaging in the gray matter structures such as the globus pallidus and in various regions of cerebral white matter. The focus of investigation has since shifted to observation of cerebral white matter areas that are more frequently detected on MR imaging and are more responsible for chronic symptoms than the gray matter. DWI has dramatically contributed to the ability to quantitatively assess cerebral white matter damage. Subsequently, DTI has enabled more sensitive evaluation than DWI and can demonstrate progressive pathologic changes in the early stage, allowing prediction of chronic conditions. In addition, MR spectroscopy reveals changes in metabolite levels, offering quantitative clinicopathologic information on brain damage after carbon monoxide poisoning.

Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = -.70; r = -.75), bilateral PF (r = -.66; r = -.68), and MWT (r = -.71; r = -.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

Prediction of individual subject's age across the human lifespan using diffusion tensor imaging: A machine learning approach

Diffusion tensor imaging has the potential to be used as a neuroimaging marker of natural ageing and assist in elucidating trajectories of cerebral maturation and ageing. In this study, we applied a multivariate technique relevance vector regression (RVR) to predict individual subject's age using whole brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) from a cohort of 188 subjects aged 4-85 years. High prediction accuracy as derived from Pearson correlation coefficient of actual versus predicted age (FA - r=0.870 p<0.0001; MD - r=0.896 p<0.0001; AD - r=0.895 p<0.0001; RD - r=0.899 p<0.0001) was achieved. Cerebral white-matter regions that contributed to these predictions include; corpus callosum, cingulum bundles, posterior longitudinal fasciculus and the cerebral peduncle. A post-hoc analysis of these regions showed that FA follows a nonlinear rational-quadratic trajectory across the lifespan peaking at approximately 21.8 years. The MD, RD and AD volumes were particularly useful for making predictions using grey matter cerebral regions. These results suggest that diffusion tensor imaging measurements can reliably predict individual subject's age and demonstrate that FA cerebral maturation and ageing patterns follow a non-linear trajectory with a noteworthy peaking age. These data will contribute to the understanding of neurobiology of cerebral maturation and ageing. Most notably, from a neuropsychiatric perspective our results may allow differentiation of cerebral changes that may occur due to natural maturation and ageing, and those due to developmental or neuropsychiatric disorders.

Myelin water imaging reflects clinical variability in multiple sclerosis

Whilst MRI is routinely used for the assessment and diagnosis of multiple sclerosis, there is poor correspondence between clinical disability in primary progressive multiple sclerosis (PPMS) patients and conventional MRI markers of disease activity (e.g., number of enhancing lesions). As PPMS patients show diffuse and global myelin loss, the aim of this study was to evaluate the efficacy of whole-brain myelin water fraction (MWF) imaging in PPMS. Specifically, we sought to use full-brain analysis techniques to: 1) determine the reproducibility of MWF estimates in PPMS brain; 2) compare MWF values in PPMS brain to healthy controls; and 3) establish the relationship between MWF and clinical disability, regionally and globally throughout the brain. Seventeen PPMS patients and seventeen age-matched controls were imaged using a whole-brain multi-component relaxation imaging technique to measure MWF. Analysis of MWF reduction was performed on three spatial levels: 1) histogram; 2) white matter skeleton; and 3) voxel-wise at the single-subject level. From histogram analysis, PPMS patients had significantly reduced global normal appearing white matter MWF (6%, p=0.04) compared to controls. Focal lesions showed lower MWF values than white matter in controls (61%, p<0.001) and patients (59%, p<0.001). Along the white matter skeleton, MWF was diffusely reduced throughout the PPMS brain, with significant correlations between reduced MWF and increased clinical disability (more severe symptoms), as measured by the Expanded Disability Status Scale, within the corpus callosum and frontal, temporal, parietal and occipital white matter. Correlations with the more specific mental and sensory functional system scores were localized to clinically eloquent locations: reduced MWF was significantly associated with increased mental scores in anterior regions (i.e., frontal lobes and genu of the corpus callosum), and increased sensory scores in more posterior regions closer to the sensory cortex. Individual patient MWF maps were also compared to a normative population atlas, which highlighted areas of statistical difference between the individual patient and the population mean. A significant correlation was found between the volume of significantly reduced MWF and clinical disability (p=0.008, R=0.58). Our results show that clinical disability is reflected in particular regions of cerebral white matter that are consistent between subjects, and illustrates a method to examine tissue alteration throughout the brain of individual patients. These results strongly support the use of MWF imaging to evaluate disease activity in PPMS.

Clinical contributors to cerebral white matter integrity in HIV-infected individuals

HIV-infected people frequently exhibit brain dysfunction characterized by preferential damage to the cerebral white matter. Despite suppressed viral load and reconstituted immune function afforded by combination antiretroviral therapy (CART), brain dysfunction continues to be observed even in medically stable individuals. To provide insight into the etiology of HIV-associated brain dysfunction in the CART era, we examined the effects of HIV disease markers, antiretroviral treatment, hepatitis C (HCV) coinfection, and age on DTI measures of white matter integrity in a cohort of 85 individuals aged 23 to 65 years with chronic HIV infection. Fractional anisotropy and mean diffusivity were derived from 29 cerebral white matter regions, which were segmented on each individual brain using a high-resolution T1-weighted image and registered to diffusion images. Significant effects of clinical variables were found on white matter abnormalities in nearly all brain regions examined. Most notably, HCV coinfection and older age were associated with decreased anisotropy or increased diffusivity in the majority of brain regions. Individuals with higher current CD4 levels exhibited higher anisotropy in parietal lobe regions, while those undergoing antiretroviral treatment exhibited higher anisotropy in temporal lobe regions. The observed diffuse pattern of white matter injury suggests that future neuroimaging studies should employ methodologies that are not limited to circumscribed regions of interest. The current findings underline the multifactorial nature of HIV-associated brain dysfunction in the CART era, and the importance of examining the effects of HIV disease in the context of other comorbidities, in particular HCV coinfection and aging.

Detecting damaged regions of cerebral white matter in the subacute phase after carbon monoxide poisoning using voxel-based analysis with diffusion tensor imaging

The present study aimed to detect the main regions of cerebral white matter (CWM) showing damage in the subacute phase for CO-poisoned patients with chronic neurological symptoms using voxel-based analysis (VBA) with diffusion tensor imaging (DTI). Subjects comprised 22 adult CO-poisoned patients and 16 age-matched healthy volunteers as controls. Patients were classified into patients with transient acute symptoms only (group A) and patients with chronic neurological symptoms (group S). In all patients, DTI covering the whole brain was performed with a 3.0-T magnetic resonance imaging system at 2 weeks after CO exposure. As procedures for VBA, all fractional anisotropy (FA) maps obtained from DTI were spatially normalized, and FA values for all voxels in the whole CWM on normalized FA maps were statistically compared among the two patient groups and controls. Voxels with significant differences in FA were detected at various regions in comparisons between groups S and A and between group S and controls. In these comparisons, more voxels were detected in deep CWM, including the centrum semiovale, than in other regions. A few voxels were detected between group A and controls. Absolute FA values in the centrum semiovale were significantly lower in group S than in group A or controls. VBA demonstrated that CO-poisoned patients with chronic neurological symptoms had already suffered damage to various CWM regions in the subacute phase. In these regions, the centrum semiovale was suggested to be the main region damaged in the subacute phase after CO inhalation.

Altering Cortical Connectivity: Remediation-Induced Changes in the White Matter of Poor Readers

Neuroimaging studies using diffusion tensor imaging (DTI) have revealed regions of cerebral white matter with decreased microstructural organization (lowerfractional anisotropy or FA) among poor readers. We examined whether 100 hr of intensive remedial instruction affected the white matter of 8- to 10-year-old poor readers. Prior to instruction, poor readers had significantly lower FA than good readers in a region of the left anterior centrum semiovale. The instruction resulted in a change in white matter (significantly increased FA), and in the very same region. The FA increase was correlated with a decrease in radial diffusivity (but not with a change in axial diffusivity), suggesting that myelination had increased. Furthermore, the FA increase was correlated with improvement in phonological decoding ability, clarifying the cognitive locus of the effect. The results demonstrate the capability of a behavioral intervention to bring about a positive change in cortico-cortical white matter tracts.

Specific relations between neurodevelopmental abilities and white matter microstructure in children born preterm

Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28(+5) (24(+4)-32(+1)) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24-27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales [giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal-social, hearing-language, eye-hand coordination and performance scales] at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye-hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and provide a biomarker for therapeutic or mechanistic studies of preterm brain injury.

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

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. Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Voxel-based morphometry of unilateral temporal lobe epilepsy reveals abnormalities in cerebral white matter

Voxel-based morphometric (VBM) investigations of temporal lobe epilepsy have focused on the presence and distribution of gray matter abnormalities. VBM studies to date have identified the expected abnormalities in hippocampus and extrahippocampal temporal lobe, as well as more diffuse abnormalities in the thalamus, cerebellum, and extratemporal neocortical areas. To date, there has not been a comprehensive VBM investigation of cerebral white matter in nonlesional temporal lobe epilepsy. This study examined 25 lateralized temporal lobe epilepsy patients (13 left, 12 right) and 62 healthy controls in regard to both temporal and extratemporal lobe gray and white matter. Consistent with prior reports, gray matter abnormalities were evident in ipsilateral hippocampus and ipsilateral thalamus. Temporal and extratemporal white matter was affected ipsilateral to the side of seizure onset, in both left and right temporal lobe epilepsy groups. These findings indicate that chronic temporal lobe epilepsy is associated not only with abnormalities in gray matter, but also with concomitant abnormalities in cerebral white matter regions that may affect connectivity both within and between the cerebral hemispheres.

Magnetisation transfer ratio of normal brain white matter: a normative database spanning four decades of life.

OBJECTIVES: To establish a normative database for magnetisation transfer ratio (MTR) measurements in the white matter of healthy adult brains. Such MTR values were evaluated for regional variation and evidence...

White matter changes and ventricular enlargement on magnetic resonance imaging: Comparison between normal elderly subjects and patients with cerebrovascular disorders

T2-weighted magnetic resonance imaging has been shown to be effective in detecting changes in cerebral white matter. High signal intensity in cerebral white matter regions has been suggested to be indicative of the presence of a disease state. In normal aging, white matter changes, known as leuko-araiosis, have been reported to be widespread. Some studies have linked leuko-araiosis to aging and risk factors for stroke. There is also evidence that changes in cerebral white matter occur in hydrocephalus and that enlargement of the lateral ventricles is a byproduct of severe white matter changes. This study reports data on the frequency and severity of leuko-araiosis in normal subjects and patients with cerebrovascular disease and explores the relationship between white matter changes and ventricular dilatation.