Related Articles

Magnetic resonance imaging of cortical lesions due to multiple sclerosis (MS) has been hampered by the lesions' small size and low contrast to adjacent, normal-appearing tissue. Knowing cortical lesion T1 and proton density (PD) would be highly beneficial for the process of developing and optimizing dedicated magnetic resonance (MR) sequences through computer modeling of MR tissue responses. Eight patients and seven healthy control subjects were scanned at 7 T using a series of inversion recovery turbo field echo scans with varying inversion times. Regions of interest were drawn in white matter, gray matter, cortical lesions, white matter lesions and cerebrospinal fluid. White matter and gray matter T1s were significantly higher in MS patients than in controls. Cortical and white matter lesion T1 and PD are also presented for the first time. The advantages of ultrahigh field MR imaging will be important for future investigations in MS research and sequence optimization for the detection of cortical lesions.

Background

In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load.

Objective

We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability.

Methods

Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T2-weighted lesion load.

Results

Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1–8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (rs = −0.49; P = 0.001) and multiple sclerosis functional score (rs = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures.

Conclusion

Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis.

White matter fiber bundles form a spatial pattern defined by anatomical and functional architecture. Structural lesions in the white matter may cause clinical symptoms because of disruption of fiber tracts. The clinical significance will depend on the anatomic location of such lesions and whether the functional integrity of specific fiber bundles is affected. Unlike more acute lesions of stroke or multiple sclerosis that may cause sudden sensorimotor deficits, white matter lesions of aging manifest with more subtle and gradual symptoms that are often cognitive in nature. Such cognitive symptoms have been explained by strategically located white matter lesions in the deep forebrain that may disrupt cholinergic projection fibers at their proximal origin. Recent in vivo imaging studies provide supportive evidence that periventricular white matter lesions are associated with cortical cholinergic deafferentation in elderly with leukoaraiosis. White matter lesions at the frontal horns, so-called “capping,” are in close proximity to cholinergic axons that originate in the basal forebrain. Therefore, these lesions may result in more significant cortical deafferentation because of the more proximal axonal disruption. A unique anatomic feature common to all cortical projections from subcortical neuromodulator systems (that not only include the cholinergic but also the monoaminergic systems, such as dopamine, serotonin, and norepinephrine) is that the proximal axons largely pass through the deep forebrain before fanning out to the cortex. It is thus plausible that deep frontal white matter lesions may result in not only cholinergic but also variable monoaminergic cortical deafferentation.

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect.

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing–remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing–remitting multiple sclerosis (Expanded Disability Status Scale range 1.0–6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.

Background. Although grey matter pathology is a relevant aspect of multiple sclerosis (MS) both with physical and cognitive rebounds, its pathogenesis is still under investigation. To what extent the familial and sporadic cases of MS differ in cortical pathology has not been elucidated yet. Here we present a multiple case report of four sisters affected by MS, all of them having a very high burden of cortical pathology. Methods. The clinical and grey matter MRI parameters of the patients were compared with those of twenty-five-aged matched healthy women and 25 women affected by sporadic MS (matched for age, disease duration, EDSS, and white matter lesion load). Results. Despite their short disease duration (<5 years), the four sisters showed a significant cortical thinning compared to healthy controls (P = 0.003) and sporadic MS (P = 0.041) and higher CLs number (P < 0.001) and volume (P < 0.001) compared to sporadic MS. Discussion. Although limited to a single family, our observation is worth of interest since it suggests that familial factors may account for a peculiar involvement of the cortex in MS pathology. This hypothesis should be further evaluated in a large number of multiplex MS families.

OBJECTIVES—Quantitative measurement of lesion load on proton density or T2 weighted brain MRI in multiple sclerosis is a widely used marker of disease progression in treatment trials and natural history studies. However, it has proved difficult to obtain highly reproducible measurements. Several factors account for this, one of which is uncertainties in lesion identification, particularly very small white matter abnormalities. This paper aims to ascertain the significance of very small white matter abnormalities in the measurement of lesion load in multiple sclerosis.
METHODS—All visible lesion areas identified by an experienced observer on proton density weighted spin echo brain MRI with 5 mm thick slices were measured by using a contouring technique in 15 patients with secondary progressive multiple sclerosis (SPMS) and 13 with relapsing remitting multiple sclerosis (RRMS). The size distribution of these lesions was analysed.
RESULTS—80% of the number of the lesions were smaller than 80 mm2. Lesions that were smaller than 10 mm2 (equivalent diameter <3.5 mm) made up nearly 20% of all lesions; their relative contribution to the total lesion load varied from 0.0-5.7% (mean=1.1%, median=0.65%) in individual patients, and was larger when the total lesion load was smaller (r = −0.65, P<0.001). Median lesion size was significantly smaller in the SPMS group than the RRMS group.
CONCLUSIONS—The results suggest that it is prudent to identify and measure small lesions in evaluating treatment effects, and that measures are undertaken (for example, using thinner slices such as 3 mm) to improve their detection.



Background

Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking.

Aims

To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania.

Method

Eighteen patients with DSM–IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry.

Results

Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally.

Conclusions

Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.

OBJECTIVE—To assess the feasibility of a new technique based on diffusion anisotropy to segment white and grey matter of the brain. To use this technique to measure the mean diffusivity (&Dmacr;) and magnetisation transfer ratio (MTR) of normal appearing white matter (NAWM) and grey matter (NAGM) from patients with multiple sclerosis.
METHODS—Dual echo turbo spin echo, MT, and diffusion weighted scans of the brain were obtained from 30 patients with multiple sclerosis and 18 sex and age matched healthy controls. After image coregistration and removal of T2 visible lesions, white and grey matter were segmented from 10 supratentorial slices using diffusion anisotropy thresholds. Histograms of the average MTR and &Dmacr; were created for normal white and grey matter of controls and NAWM and NAGM of patients with multiple sclerosis.
RESULTS—All the MTR histogram derived metrics of the NAWM from patients with multiple sclerosis were significantly lower than those of white matter from controls. The peak height of the &Dmacr; histogram of NAWM from patients with multiple sclerosis was also significantly different from that of normal white matter. The average MTR, the peak location of the MTR histogram, and peak height of the &Dmacr; histogram of the NAGM of patients with multiple sclerosis were significantly lower than the corresponding quantities of grey matter from controls.
CONCLUSIONS—A technique was developed for segmenting white and grey matter with the potential for improving the understanding of the pathophysiology of many neurological conditions. Its application to the study of multiple sclerosis confirms the presence of a diffuse tissue damage in the NAWM of these patients and suggests that subtle changes also occur in the NAGM.



Cortical lesions have recently been a focus of multiple sclerosis (MS) MR research. In this study, we present a white matter signal attenuating sequence optimized for cortical lesion detection at 7 T. The feasibility of white matter attenuation (WHAT) for cortical lesion detection was determined by scanning eight patients (four relapsing/remitting MS, four secondary progressive MS) at 7 T. WHAT showed excellent gray matter–white matter contrast, and cortical lesions were hyperintense to the surrounding cortical gray matter, The sequence was then optimized for cortical lesion detection by determining the set of sequence parameters that produced the best gray matter–cortical lesion contrast in a 10-min scan. Despite the B1 inhomogeneities common at ultra-high field strengths, WHAT with an adiabatic inversion pulse showed good cortical lesion detection and would be a valuable component of clinical MS imaging protocols.

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field.

The complex organization of connectivity in the human brain is incompletely understood. Recently, topological measures based on graph theory have provided a new approach to quantify large-scale cortical networks. These methods have been applied to anatomical connectivity data on non-human species and cortical networks have been shown to have small-world topology, associated with high local and global efficiency of information transfer. Anatomical networks derived from cortical thickness measurements have shown the same organizational properties of the healthy human brain, consistent with similar results reported in functional networks derived from resting state functional MRI and MEG data. Here we show, using anatomical networks derived from analysis of inter-regional covariation of gray matter volume in magnetic resonance imaging (MRI) data on 259 healthy volunteers, that classical divisions of cortex (multimodal, unimodal and transmodal) have some distinct topological attributes. While all cortical divisions shared non-random properties of small-worldness and efficient wiring (short mean Euclidean distance between connected regions), the multimodal network had a hierarchical organization, dominated by frontal hubs with low clustering, whereas the transmodal network was assortative. Moreover, in a sample of 203 people with schizophrenia, multimodal network organization was abnormal, as indicated by reduced hierarchy, the loss of frontal and the emergence of non-frontal hubs, and increased connection distance. We propose that the topological differences between divisions of normal cortex may represent the outcome of different growth processes for multimodal and transmodal networks; and that neurodevelopmental abnormalities in schizophrenia specifically impact multimodal cortical organization.

Background: Current magnetic resonance imaging (MRI) outcome measures such as T2 lesion load correlate poorly with disability in multiple sclerosis. Diffusion tensor imaging (DTI) of the brain can provide unique information regarding the orientation and integrity of white matter tracts in vivo.

Objective: To use this information to map the pyramidal tracts of patients with multiple sclerosis, investigate the relation between burden of disease in the tracts and disability, and compare this with more global magnetic resonance estimates of disease burden.

Methods: 25 patients with relapsing-remitting multiple sclerosis and 17 healthy volunteers were studied with DTI. An algorithm was used that automatically produced anatomically plausible maps of white matter tracts. The integrity of the pyramidal tracts was assessed using relative anisotropy and a novel measure (Lt) derived from the compounded relative anisotropy along the tracts. The methods were compared with both traditional and more recent techniques for measuring disease burden in multiple sclerosis (T2 lesion load and "whole brain" diffusion histograms).

Results: Relative anisotropy and Lt were significantly lower in patients than controls (p < 0.05). Pyramidal tract Lt in the patients correlated significantly with both expanded disability status scale (r = -0.48, p < 0.05), and to a greater degree, the pyramidal Kurtzke functional system score (KFS-p) (r = -0.75, p < 0.0001). T2 lesion load and diffusion histogram parameters did not correlate with disability.

Conclusions: Tract mapping using DTI is feasible and may increase the specificity of MRI in multiple sclerosis by matching appropriate tracts with specific clinical scoring systems. These techniques may be applicable to a wide range of neurological conditions.

Background

Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls. While all subjects were recruited to be free of alcohol dependence, structured clinical interviews revealed significant patterns of alcohol use in the patients. Structural magnetic resonance brain images were obtained from the subjects using a 1.5 Tesla GE Signa machine. Brain cortical thickness was measured with submillimeter precision at multiple finely spaced cortical locations using semi-automated post-processing (FreeSurfer). Contrast analysis of a general linear model was used to test for differences between the two groups at each cortical location. In addition to contrasting patients with controls, a number of analyses sought to identify possible confounding effects from alcohol.

Results

No significant cortical thickness differences were observed between the full patient group and controls, nor between non-drinking patients and controls. Patients with a history of co-morbid heavy alcohol use (n = 29) showed reductions in the superior-frontal right hemisphere and pre-central left hemisphere when compared to healthy controls (n = 40).

Conclusions

Amphetamine usage was associated with reduced cortical thickness only in patients co-morbid for heavy alcohol use. Since cortical thickness is but one measure of brain structure and does not capture brain function, further studies of brain structure and function in amphetamine dependence are warranted.

Objectives: Our purpose was to investigate whether differences exist in the values and temporal evolution of mean diffusivity () and fractional anisotropy (FA) of grey and white matter after human ischaemic stroke.

Methods: Thirty two patients with lesions affecting both grey and white matter underwent serial diffusion tensor magnetic resonance imaging (DT-MRI) within 24 hours, and at 4–7 days, 10–14 days, 1 month, and 3 months after stroke. Multiple small circular regions of interest (ROI) were placed in the grey and white matter within the lesion and in the contralateral hemisphere. Values of {grey}, {white}, FA{grey} and FA{white} were measured in these ROI at each time point and the ratios of ischaemic to normal contralateral values (R and FAR) calculated.

Results: and FA showed different patterns of evolution after stroke. After an initial decline, the rate of increase of {grey} was faster than {white} from 4–7 to 10–14 days. FA{white} decreased more rapidly than FA{grey} during the first week, thereafter for both tissue types the FA decreased gradually. However, FA{white} was still higher than FA{grey} at three months indicating that some organised axonal structure remained. This effect was more marked in some patients than in others. R{grey} was significantly higher than R{white} within 24 hours and at 10–14 days (p<0.05), and FAR{white} was significantly more reduced than FAR{grey} at all time points (p<0.001).

Conclusions: The values and temporal evolution of and FA are different for grey and white matter after human ischaemic stroke. The observation that there is patient-to-patient variability in the degree of white matter structure remaining within the infarct at three months may have implications for predicting patient outcome.

Brain inflammation plays a central role in multiple sclerosis (MS). Besides lymphocytes, the astroglia and microglia mainly contribute to the cellular composition of the inflammatory infiltrate in MS lesions. Several studies were able to demonstrate that cortical lesions are characterized by lower levels of inflammatory cells among activated microglia/macrophages. The underlying mechanisms for this difference, however, remain to be clarified. In the current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter. Cellular parameters were related to the expression profiles of the chemokines Ccl2 and Ccl3. We are clearly able to demonstrate that both regions are characterized by early oligodendrocyte stress/apoptosis with concomitant microglia activation and delayed astrocytosis. The extent of microgliosis/astrocytosis appeared to be greater in the subcortical white matter tract corpus callosum compared to the gray matter cortex region. The same holds true for the expression of the key chemokines Ccl2 and Ccl3. The current study defines a model to study early microglia activation and to investigate differences in the neuroinflammatory response of white vs. gray matter.

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

Aims

Marmoset experimental autoimmune encephalomyelitis (EAE) has previously been shown to replicate the essential features of both white matter and grey matter lesions of MS. This study set out to investigate whether cortical atrophy occurs in marmoset EAE and whether cortical thinning is related to the presence of focal, demyelinated cortical lesions.

Methods

17 leucocortical lesions and 13 subpial lesions were identified in 6 EAE cases. Cortical thickness surrounding these lesions was recorded and compared with matched cortical areas from 5 control animals.

Results

We found a diffuse13–21% loss of cortical thickness in all areas of EAE cortex compared with control animals but there was no additional loss seen in demyelinated verses myelinated EAE cortex. These findings could not be accounted for by effects of age, sex and disease duration.

Conclusions

These findings confirm the presence of significant cortical atrophy in this model. We conclude that localised cortical demyelination is not responsible for the major part of the atrophy observed and that cortical thinning is largely due to more diffuse or more remote factors. Marmoset EAE is an invaluable tool which can be used to further investigate the cause and the substrate of cortical loss in demyelinating diseases.

Objective

Here, we use pattern-classification to investigate diagnostic information for multiple sclerosis (MS; relapsing­remitting type) in lesioned areas, areas of normal­appearing grey matter (NAGM), and normal-appearing white matter (NAWM) as measured by standard MR techniques.

Methods

A lesion mapping was carried out by an experienced neurologist for Turbo Inversion Recovery Magnitude (TIRM) images of individual subjects. Combining this mapping with templates from a neuroanatomic atlas, the TIRM images were segmented into three areas of homogenous tissue types (Lesions, NAGM, and NAWM) after spatial standardization. For each area, a linear Support Vector Machine algorithm was used in multiple local classification analyses to determine the diagnostic accuracy in separating MS patients from healthy controls based on voxel tissue intensity patterns extracted from small spherical subregions of these larger areas. To control for covariates, we also excluded group-specific biases in deformation fields as a potential source of information.

Results

Among regions containing lesions a posterior parietal WM area was maximally informative about the clinical status (96% accuracy, p<10−13). Cerebellar regions were maximally informative among NAGM areas (84% accuracy, p<10−7). A posterior brain region was maximally informative among NAWM areas (91% accuracy, p<10−10).

Interpretation

We identified regions indicating MS in lesioned, but also NAGM, and NAWM areas. This complements the current perception that standard MR techniques mainly capture macroscopic tissue variations due to focal lesion processes. Compared to current diagnostic guidelines for MS that define areas of diagnostic information with moderate spatial specificity, we identified hotspots of MS associated tissue alterations with high specificity defined on a millimeter scale.

Background

Degenerative features such as neuronal, glial, synaptic and axonal loss have been identified in neocortical and other grey matter structures in patients with multiple sclerosis, but mechanisms for neurodegeneration are unclear. Cortical demyelinating lesions are a potential cause of this degeneration but the pathological and clinical significance of these lesions is uncertain, as they remain difficult to identify and study in vivo. In this study we aimed to describe and quantify cellular and subcellular pathology in the cortex of MOG-induced marmoset experimental autoimmune encephalomyelitis using quantitative immunohistochemical methods.

Results

We found evidence of diffuse axonal damage occurring throughout cortical grey matter with evidence for synaptic loss and gliosis and a 13.6% decrease in neuronal size and occurring in deep cortical layers. Evidence of additional axonal damage and a 29.6–36.5% loss of oligodendrocytes was found in demyelinated cortical lesions. Leucocortical lesions also showed neuronal loss of 22.2% and a 15.8% increase in oligodendrocyte size.

Conclusions

The marmoset EAE model therefore shows both focal and generalised neurodegeneration. The generalised changes cannot be directly related to focal lesions, suggesting that they either are a consequence of diffusible inflammatory factors or secondary to remote lesions acting through trans-synaptic or retrograde degeneration.

We describe a new fully automatic method for the segmentation of brain images that contain multiple sclerosis white matter lesions. Multichannel magnetic resonance images are used to delineate multiple sclerosis lesions while segmenting the brain into its major structures. The method is an atlas-based segmentation technique employing a topological atlas as well as a statistical atlas. An advantage of this approach is that all segmented structures are topologically constrained, thereby allowing subsequent processing such as cortical unfolding or diffeomorphic shape analysis techniques. Evaluation with both simulated and real data sets demonstrates that the method has an accuracy competitive with state-of-the-art MS lesion segmentation methods, while simultaneously segmenting the whole brain.

Structural delineation and assignment are the fundamental steps in understanding the anatomy of the human brain. The white matter has been structurally defined in the past only at its core regions (deep white matter). However, the most peripheral white matter areas, which are interleaved between the cortex and the deep white matter, have lacked clear anatomical definitions and parcellations. We used axonal fiber alignment information from diffusion tensor imaging (DTI) to delineate the peripheral white matter, and investigated its relationship with the cortex and the deep white matter. Using DTI data from 81 healthy subjects, we identified nine common, blade-like anatomical regions, which were further parcellated into 21 subregions based on the cortical anatomy. Four short association fiber tracts connecting adjacent gyri (U-fibers) were also identified reproducibly among the healthy population. We anticipate that this atlas will be useful resource for atlas-based white matter anatomical studies.

Regional cerebral oxygen utilisation (rCMRO2), oxygen extraction (rOER), blood flow (rCBF), and blood volume (rCBV) have been determined for fifteen patients with multiple sclerosis in remission using positron emission tomography (PET). Cerebral oxygen utilisation and blood flow were significantly reduced in both white matter and peripheral cortical grey matter in the multiple sclerosis patients compared to a group of normal controls. No evidence of regional cerebral ischaemia in the multiple sclerosis group was found. Lowest levels of cerebral oxygen utilisation were found in patients with cerebral atrophy, and in patients in whom a significant fall in present full-scale IQ from estimated pre-morbid levels had occurred. No correlation was found between rCMRO2 values and severity of locomotor dysfunction or clinical disease duration.

Images

Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.

Alterations in gray and white matter have been well documented in individuals with multiple sclerosis. Severity and extent of such brain tissue damage have been associated with cognitive impairment, disease duration and neurological disability, making quantitative indices of tissue damage important markers of disease progression. In this study, we investigated the association between cardiorespiratory fitness and measures of gray matter atrophy and white matter integrity. Employing a voxel-based approach to analyses of gray matter and white matter, we specifically examined whether higher levels of fitness in multiple sclerosis participants were associated with preserved gray matter volume and integrity of white matter. We found a positive association between cardiorespiratory fitness and regional gray matter volumes and higher focal fractional anisotropy values. Statistical mapping revealed that higher levels of fitness were associated with greater gray matter volume in the midline cortical structures including the medial frontal gyrus, anterior cingulate cortex and the precuneus. Further, we also found increasing levels of fitness were associated with higher fractional anisotropy in the left thalamic radiation and right anterior corona radiata. Both preserved gray matter volume and white-matter tract integrity were associated with better performance on measures of processing speed. Taken together, these results suggest that fitness exerts a prophylactic influence on the cerebral atrophy observed early on preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability.