Abnormalities In White Matter Tracts Research Articles

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.

White matter abnormalities in schizophrenia and schizotypal personality disorder.

Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis.

Maternal Neurofascin-Specific Autoantibodies Bind to Structures of the Fetal Nervous System during Pregnancy, but Have No Long Term Effect on Development in the Rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children.

Pattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers

BackgroundTo investigate the patterns of brain atrophy, white matter (WM) tract changes, and functional connectivity (FC) abnormalities in asymptomatic granulin (GRN) mutation carriers. MethodsTen cognitively normal subjects (five mutation carriers, GRN+; years to estimated disease onset: 12 ± 7; five mutation noncarriers, GRN−) underwent a clinical and imaging (structural, diffusion tensor, and resting-state functional magnetic resonance imaging) assessment. Brain atrophy was measured with cortical thickness analysis, WM abnormalities with tract-based spatial statistics, and FC with independent component analysis. ResultsGRN+ showed smaller cortical thickness than GRN− in the right orbitofrontal and precentral gyrus and left rostral middle frontal gyrus. WM tracts abnormalities were limited to increased axial diffusivity in the right cingulum, superior longitudinal fasciculus, and corticospinal tract. There were no differences in FC of resting-state networks. ConclusionBrain atrophy and WM tract abnormalities in frontal-parietal circuits can be detected at least a decade before the estimated symptom onset in asymptomatic mutation carriers.

Left Hemisphere Diffusivity of the Arcuate Fasciculus: Influences of Autism Spectrum Disorder and Language Impairment

There has been much discussion whether brain abnormalities associated with specific language impairment and autism with language impairment are shared or are disorder specific. Although white matter tract abnormalities are observed in both specific language impairment and autism spectrum disorders, the similarities and differences in the white matter abnormalities in these 2 disorders have not been fully determined. Diffusion tensor imaging diffusion parameters of the arcuate fasciculus were measured in 14 children with specific language impairment as well as in 16 children with autism spectrum disorder with language impairment, 18 with autism spectrum disorder without language impairment, and 25 age-matched typically developing control participants. Language impairment and autism spectrum disorder both had (elevating) main effects on mean diffusivity of the left arcuate fasciculus, initially suggesting a shared white matter substrate abnormality. Analysis of axial and radial diffusivity components, however, indicated that autism spectrum disorder and language impairment differentially affect white matter microstructural properties, with a main effect of autism spectrum disorder on axial diffusivity and a main effect of language impairment on radial diffusivity. Although white matter abnormalities appear similar in language impairment and autism spectrum disorder when examining broad white matter measures, a more detailed analysis indicates different mechanisms for the white matter microstructural anomalies associated with language impairment and autism spectrum disorder.

Distributed corpus callosum involvement in amyotrophic lateral sclerosis: a deterministic tractography study using q-ball imaging

Diffusion tensor imaging (DTI) has become a useful tool for investigating early white matter (WM) abnormalities in motor neuron disease. Furthermore, fiber tracking packages that apply multi-tensorial algorithms, such as q-ball imaging (QBI), have been proposed as alternative approaches to overcome DTI limitations in depicting fiber tracts with different orientations within the same voxel. We explored motor and extra-motor WM tract abnormalities in phenotypically heterogeneous amyotrophic lateral sclerosis (ALS) cases aiming to establish a consistent QBI-based WM signature of disease. We performed a whole-brain, QBI tract-based spatial statistics analysis with deterministic tractography of genu, body and splenium of corpus callosum (CC) and corticospinal tracts (CST) in 20 ALS patients (12 classical and 8 lower motor neuron variants) compared to 20 healthy controls. Mean tract length, fiber volume and density, and generalized fractional anisotropy were extracted and related to clinical indices of pyramidal impairment (upper motor neuron score), disease disability (ALS functional rating scale-revised) and progression. ALS patients showed significantly decreased fiber density and volume, and increased tract length in all regions of CC and left CST (p < 0.05, corrected). In CC body, pyramidal impairment was inversely correlated to fiber density (p = 0.01), while in CC splenium, clinical disability (p = 0.01) and progression (p = 0.02) were inversely correlated to tract length. Our findings further suggest that QBI tractography might represent a promising approach for investigating structural alterations in neurodegenerative diseases and confirm that callosal involvement is a consistent feature of most ALS variants, significantly related to both pyramidal dysfunction and disease disability.

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p < .05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occipital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciculus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions.

Review of functional and anatomical brain connectivity findings in schizophrenia

We review diffusion tensor imaging (DTI) studies that investigate white matter abnormalities in patients with chronic schizophrenia, first episode schizophrenia, and those who are at genetic risk for developing schizophrenia. Additionally, we include studies that combine DTI and functional MRI (fMRI) to investigate brain connectivity abnormalities. Schizophrenia is a complex mental disorder with a peak age of onset in early adulthood. Abnormalities in white matter tracts, which connect brain regions into functional networks, are most likely relevant for understanding structural and functional brain abnormalities in schizophrenia. Dysconnectivity between brain regions, in fact, is thought to underlie cognitive abnormalities in schizophrenia but little is known about how alterations at the functional level relate to abnormalities in anatomical connectivity. DTI has become one of the most popular tools in brain research to address such questions. Here we review white matter abnormalities using DTI with the aim of understanding dysconnectivity of brain regions and their implications in schizophrenia. Advances in DTI and in combining DTI with fMRI provide new insight into anatomical and functional connections in the brain, and for studying dysconnectivity in schizophrenia.

White matter tract abnormalities between rostral middle frontal gyrus, inferior frontal gyrus and striatum in first-episode schizophrenia

BackgroundPrevious studies have shown that frontostriatal networks, especially those involving dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) mediate cognitive functions some of which are abnormal in schizophrenia. This study examines white matter integrity of the tracts connecting DLPFC/VLPFC and striatum in patients with first-episode schizophrenia (FESZ), and their associations with cognitive and clinical correlates. MethodsDiffusion tensor and structural magnetic resonance images were acquired on a 3T GE Echospeed system from 16 FESZ and 18 demographically comparable healthy controls. FreeSurfer software was used to parcellate regions of interest. Two-tensor tractography was applied to extract fibers connecting striatum with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. DTI indices, including fractional anisotropy (FA), trace, axial diffusivity (AD) and radial diffusivity (RD), were used for group comparisons. Additionally, correlations were evaluated between these diffusion indices and the Wisconsin Card Sorting Task (WCST) and the Brief Psychiatric Rating Scale (BPRS). ResultsFA was significantly reduced in the left IFG–striatum tract, whereas trace and RD were significantly increased in rMFG–striatum and IFG–striatum tracts, bilaterally. The number of WCST categories completed correlated positively with FA of the right rMFG–striatum tract, and negatively with trace and RD of right rMFG–striatum and right IFG–striatum tracts in FESZ. The BPRS scores did not correlate with these indices. ConclusionsThese data suggest that white matter tract abnormalities between rMFG/IFG and striatum are present in FESZ and appear to be significantly associated with executive dysfunction but not with symptom severity.

White matter microstructural abnormalities in bipolar disorder: A whole brain diffusion tensor imaging study

BackgroundBipolar disorder (BD) is a chronic mental illness characterized by severe disruptions in mood and cognition. Diffusion tensor imaging (DTI) studies suggest that white matter (WM) tract abnormalities may contribute to the clinical hallmarks of the disorder. Using DTI and whole brain voxel-based analysis, we mapped the profile of WM anomalies in BD. All patients in our sample were euthymic and lithium free when scanned.MethodsDiffusion-weighted and T1-weighted structural brain images were acquired from 23 lithium-free euthymic subjects with bipolar I disorder and 19 age- and sex-matched healthy control subjects on a 1.5 T MRI scanner. Scans were processed to provide measures of fractional anisotropy (FA) and mean and radial diffusivity (MD and RD) at each WM voxel, and processed scans were nonlinearly aligned to a customized brain imaging template for statistical group comparisons.ResultsRelative to controls, the bipolar group showed widespread regions of lower FA, including the corpus callosum, cortical and thalamic association fibers. MD and RD were abnormally elevated in patients in many of these same regions.ConclusionsOur findings agree with prior reports of WM abnormalities in the corpus callosum and further link a bipolar diagnosis with structural abnormalities of the tapetum, fornix and stria terminalis. Future studies assessing the diagnostic specificity and prognostic implications of these abnormalities would be of interest.

Conventional magnetic resonance imaging and diffusion tensor imaging studies in children with novel GPR56 mutations: further delineation of a cobblestone-like phenotype

GPR56-related bilateral frontoparietal polymicrogyria (BFPP) is a rare recessively inherited disorder of neuronal migration caused by mutations of GPR56. To better delineate the clinical, molecular, and neuroradiological phenotypes associated with BFPP, we performed conventional magnetic resonance imaging and diffusion tensor imaging studies in a series of prospectively enrolled patients carrying novel GPR56 mutations. All subjects with GPR56-related BFPP showed a characteristic morphological pattern, including abnormalities of the cerebellar cortex with cerebellar cysts located at the periphery, a mildly thick corpus callosum, and a flat pons. Significant alterations of myelination and white matter tract abnormalities were documented. The present study confirms the phenotypic overlap between GPR56-related brain dysgenesis and other cobblestone-like syndromes and illustrates the contribution of 3D neuroimaging in the characterization of malformations of cortical development.

Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study.

OBJECTIVETo examine whether type 2 diabetes is associated with microstructural abnormalities in specific cerebral white matter tracts and to relate these microstructural abnormalities to cognitive functioning.RESEARCH DESIGN AND METHODSThirty-five nondemented older individuals with type 2 diabetes (mean age 71 ± 5 years) and 35 age-, sex-, and education-matched control subjects underwent a 3 Tesla diffusion-weighted MRI scan and a detailed cognitive assessment. Tractography was performed to reconstruct several white matter tracts. Diffusion tensor imaging measures, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups and related to cognitive performance.RESULTSMD was significantly increased in all tracts in both hemispheres in patients compared with control subjects (P < 0.05), reflecting microstructural white matter abnormalities in the diabetes group. Increased MD was associated with slowing of information-processing speed and worse memory performance in the diabetes but not in the control group after adjustment for age, sex, and estimated IQ (group × MD interaction, all P < 0.05). These associations were independent of total white matter hyperintensity load and presence of cerebral infarcts.CONCLUSIONSIndividuals with type 2 diabetes showed microstructural abnormalities in various white matter pathways. These abnormalities were related to worse cognitive functioning.

White matter tract abnormalities in first-episode psychosis

Fibers connecting fronto-temporal and fronto-medial structures that pass through the anterior limb of the internal capsule (ALIC) subserve executive and psychomotor functioning. Both of these functions are adversely affected in schizophrenia, and may be abnormal at illness onset. In a study of first-episode psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to examine ALIC integrity. Fourteen early psychosis patients and 29 healthy volunteers were included. Symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE Signa 1.5T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was acquired for manual seeding in structural space. Diffusion tensor imaging (DTI) was performed, and all DTI images were co-registered to structural space. Seeds were manually drawn bilaterally on the coronal plane at a specified location. Diffusion images were post-processed for subsequent Tract-based Spatial Statistics (TBSS) analysis. First-episode psychosis patients had significantly smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy volunteers on the left and the right (p-values<0.04). No differences in mean fractional anisotropy (FA) were seen within either left or right tracts (p-values>0.05), nor did TBSS reveal any other differences in FA values between groups in other regions. Relationships between tract volumes and symptom severity were not observed in this study.

SU-E-I-73: Gray Matter Atrophy and White Matter Tract Abnormalities by Voxel Wise Correlation Analysis in Patients with Alzheimer's Disease.

We evaluated the relationship between white matter (WM) tract disintegration and gray matter (GM) atrophy in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, using diffusion tensor imaging (DTI) and an optimized voxel-based analysis. Two hundred thirty one individuals (61 controls, 116 MCI and 54 AD) were included. Voxel-based WM tract statistics was used to obtain whole-brain maps of WM bundles for FA. Voxel-based morphometry (VBM) was conducted to detect regions of gray matter (GM) atrophy in the AD, MCI group relative to the control group. FA maps were processed to make voxel-wise comparison of tract based analysis in whole brain between each the two groups. The relationship between locations of abnormalities in the WM and GM were examined. Patients with AD showed significant GM atrophy in posterior cingulate gyrus (BA31, 32) to the precuneus, the middle temporal lobe (BA19), the superior frontal (BA9) to the anterior cingulate (BA 32), the medial frontal lobe (BA 11, BA25), the hippocampus, the parahippocampal gyrus (BA30/34) and the insula, and WM tract disintegrity of the uncinate fasciculus, posterior cingulate fasciculus and fornix compared with the control and MCI groups. These abnormalities in the AD group were caused by either structural changes in GM atrophy or neural dysfunction due to functional disconnections in the WM tract. The GM atrophy resulting from WM tract disintegration or GM atrophy itself may be the first step in the AD process, resulting in anatomically congruent correlations between WM disintegration and regional GM atrophy. Using tract based spatial statistics and voxel based analysis, both of which are useful in investigating GM and WM changes in individuals with neurodegenerative disorders.

White and Gray Matter Changes in Early Multiple Sclerosis (P03.049)

Objective: To evaluate damage in white and gray matter during early stages of relapsing-remitting multiple sclerosis (MS-RR). Background MS is an autoimmune, inflammatory CNS disease. Early in the disease, patients report significant problems in both physical and cognitive tasks. There is a paucity of literature on the extent of damage that occurs in patients even during the early stages of MS. This study further explores areas of the brain that are most affected in the early stages of RRMS. Design/Methods: Subjects included 9 controls (ages 26-48) and 20 MS patients (ages 22-45). MS patients had onset of symptoms Results: Compared to controls, MS patients showed significant FA white matter tract abnormalities in the corpus callosum, frontal, parietal, fornix, and thalamic tracts (P Conclusions: MS patients showed significant abnormalities both in the normal appearing white and gray matter structures. This study underscores the extent of damage both in the white and gray mater even in this early stage of MS and argues for early treatment of these patients. Disclosure: Dr. Williamson has received personal compensation for activities with Accorda Therapeutics as a participant on an advisory board. Dr. Shi has nothing to disclose. Dr. Javed has received personal compensation for activities with Teva Neuroscience, Bayer Pharmaceuticals, Serono, Inc., Novartis, Questcor and Biogen Idec as a consultant and/or speaker.

P-805 - Diffusion tensor imaging (DTI) findings in schizophrenia: what's new?

Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that have increasingly being used for the non-invasive evaluation of brain white matter (WM) abnormalities.Several studies suggest that the normal integration of cerebral function may be compromised in schizophrenia. Abnormalities in WM tracts may be directly relevant for the neuropathology of schizophrenia The purpose of this review was to discuss recent DTI findings in schizophrenia and a methodologic analysis. The literature search was performed with the search engine PubMed of the U.S. National Library of Medicine.Search strategy used was based on the Cochrane review technique, limited to the period between 1998 (first report on DTI and schizophrenia) and October 2011. And limited to ‘Title/Abstract’..The reference lists of these studies were used to identify additional studies. There is a striking amount of heterogeneity in findings, probably by methodologic problems.Brain regions such as the cingulate bundle,corpus callosum, and regions within frontal and temporal WM have a proportionally larger number of positive findings across the studies.In addition,WM tracts as The superior longitudinal fasciculus, fronto-occipital longitudinal fasciculi, uncinate fasciculi,frontal longitudinal fasciculus and the arcuate fasciculus have also positive findings in patients with schizophrenia. Other brain structures as the cerebellar peduncles,the fornix,the hippocampus and parahippocampal gyrus, the thalamic and optic radiations have been evaluated and shown positive findings. However, these findings are not present in all studies.DTI abnormalities in first-episode patients are less robust than in chronic patients. Recent DTI findings seem to support the hypothesis of structural dysconnectivity in schizophrenia.

Frontal White Matter Integrity Predictors of Adult Alcohol Treatment Outcome

Previous research has associated abnormalities in frontal lobe functioning with alcohol relapse. In this study, we used diffusion tensor imaging to investigate whether frontal white matter integrity measured at the start of treatment differs between persons with alcohol use disorders (AUD) who sustain treatment gains and those who return to heavy use after treatment. Forty-five treatment-seeking AUD inpatients and 30 healthy control subjects were included in the study. Six months after completing treatment, 16 of the AUD participants had resumed heavy use (RHU) and 29 others remained abstinent or drank minimally (treatment sustainers [TS]). Voxel-wise group comparisons (TS vs. RHU) were performed on fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity maps generated from each subject's diffusion tensor imaging scan at the start of treatment. We found significantly lower FA and significantly higher RD in the frontal lobes of the RHU group, relative to the TS group. The RHU group data are consistent with previous reports of abnormal frontal white matter tract abnormalities in persons with AUD. It is possible that the lower FA and higher RD in the RHU group reflect microstructural injury to frontal circuitries, and these may underlie the reduced cognitive control amid heightened reward sensitivity associated with resumption of heavy drinking.

Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts

Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included.

Multiple white matter tract abnormalities underlie cognitive impairment in RRMS

Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40 ± 0.03 vs. 0.43 ± 0.01, p<0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease.

Diffusion MRI in corticofugal fibers correlates with hand function in unilateral cerebral palsy

Diffusion MRI improves detection of abnormalities in white matter tracts in cerebral palsy (CP). Relationships between diffusion measurements and hand function are largely unexplored. We aimed first to assess microstructure of corticofugal fibers, and second to explore associations between tract injury as assessed by quantitative analysis of diffusion MRI and hand function in children with unilateral CP. In this cross-sectional study, 15 children with unilateral CP (6 boys, median age 12.4 years, min 7.2, max 17) and 24 controls were included (9 boys, median age 12.7 years, min 8.8, max 17.3). Hand function was assessed with the Box and Blocks (B&B) test. Magnetic resonance diffusion data (b value = 1,000 s/mm(2), 45 directions) were collected on a 1.5-T scanner. Fractional anisotropy (FA), mean diffusivity (MD), and tensor eigenvalues were measured bilaterally in the cerebral peduncle (ROI1), the posterior limb of the internal capsule (PLIC, ROI2), and corticofugal fibers connecting these regions. In children with CP, FA in both ROIs and the partial tract corresponding to the affected hand was significantly lower compared to controls. This was caused by an increase in diffusivity perpendicular to the tract. After controlling for age, mean FA contralateral to the affected hand correlated with B&B scores, which was independent of lesion type or number of voxels in the partial tract, cerebral peduncle, or PLIC. FA in corticofugal fibers is a sensitive marker of damage to the motor system and correlates with hand function in CP. Using FA may improve early prediction of outcome.