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Background: Classification models based on magnetic resonance imaging (MRI) may aid early diagnosis of frontotemporal dementia (FTD) but have only been applied in established FTD cases. Detection of FTD patients in earlier disease stages, such as presymptomatic mutation carriers, may further advance early diagnosis and treatment. In this study, we aim to distinguish presymptomatic FTD mutation carriers from controls on an individual level using multimodal MRI-based classification. Methods: Anatomical MRI, diffusion tensor imaging (DTI) and resting-state functional MRI data were collected in 55 presymptomatic FTD mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12 chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey and white matter density features from anatomical MRI scans, diffusivity features from DTI, and functional connectivity features from resting-state functional MRI. These features were applied in a recently introduced multimodal behavioural variant FTD (bvFTD) classification model, and were subsequently used to train and test unimodal and multimodal carrier-control models. Classification performance was quantified using area under the receiver operator characteristic curves (AUC). Results: The bvFTD model was not able to separate presymptomatic carriers from controls beyond chance level (AUC = 0.570, p = 0.11). In contrast, one unimodal and several multimodal carrier-control models performed significantly better than chance level. The unimodal model included the radial diffusivity feature and had an AUC of 0.646 (p = 0.021). The best multimodal model combined radial diffusivity and white matter density features (AUC = 0.680, p = 0.005). Conclusions: FTD mutation carriers can be separated from controls with a modest AUC even before symptom-onset, using a newly created carrier-control classification model, while this was not possible using a recent bvFTD classification model. A multimodal MRI-based classification score may therefore be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of white matter features in the best performing model suggests that the earliest FTD-related pathological processes occur in white matter.

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Background: Diffusion Tensor Imaging (DTI) can evaluate microstructural tissue damage in the optic radiation (OR) of patients with clinically isolated syndrome (CIS), early relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorders (NMOSD). Different post-processing techniques, e.g. tract-based spatial statistics (TBSS) and probabilistic tractography, exist to quantify this damage. Objective: To evaluate the capacity of TBSS-based atlas region-of-interest (ROI) combination with 1) posterior thalamic radiation ROIs from the Johns Hopkins University atlas (JHU-TBSS), 2) Juelich Probabilistic ROIs (JUEL-TBSS) and tractography methods using 3) ConTrack (CON-PROB) and 4) constrained spherical deconvolution tractography (CSD-PROB) to detect OR damage in patients with a) NMOSD with prior ON (NMOSD-ON), b) CIS and early RRMS patients with ON (CIS/RRMS-ON) and c) CIS and early RRMS patients without prior ON (CIS/RRMS-NON) against healthy controls (HCs). Methods: Twenty-three NMOSD-ON, 18 CIS/RRMS-ON, 21 CIS/RRMS-NON, and 26 HCs underwent 3 T MRI. DTI data analysis was carried out using JUEL-TBSS, JHU-TBSS, CON-PROB and CSD-PROB. Optical coherence tomography (OCT) and visual acuity testing was performed in the majority of patients and HCs. Results: Absolute OR fractional anisotropy (FA) values differed between all methods but showed good correlation and agreement in Bland-Altman analysis. OR FA values between NMOSD and HC differed throughout the methodologies (p-values ranging from p < 0.0001 to 0.0043). ROC-analysis and effect size estimation revealed higher AUCs and R2 for CSD-PROB (AUC = 0.812; R2 = 0.282) and JHU-TBSS (AUC = 0.756; R2 = 0.262), compared to CON-PROB (AUC = 0.742; R2 = 0.179) and JUEL-TBSS (AUC = 0.719; R2 = 0.161). Differences between CIS/RRMS-NON and HC were only observable in CSD-PROB (AUC = 0.796; R2 = 0.094). No significant differences between CIS/RRMS-ON and HC were detected by any of the methods. Conclusions: All DTI post-processing techniques facilitated the detection of OR damage in patient groups with severe microstructural OR degradation. The comparison of distinct disease groups by use of different methods may lead to different - either false-positive or false-negative - results. Since different DTI post-processing approaches seem to provide complementary information on OR damage, application of distinct methods may depend on the relevant research question.

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Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes. Methods: We enrolled a unique cohort of patients with SCA1 (n = 15), SCA2 (n = 12), SCA3 (n = 20) and SCA7 (n = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters. Results: Clinical scores worsened as atrophy increased over time (p < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics. Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.

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Very low birth weight (VLBW: ≤ 1500 g) individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT) and diffusion tensor imaging (DTI). Probabilistic tractography of motor pathways of the corticospinal tract (CST) and corpus callosum (CC) was performed. Fractional anisotropy (FA) was calculated in non-crossing (capsula interna in CST, body of CC) and crossing (centrum semiovale) fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS) was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within the VLBW group. In the TBSS analysis, the VLBW group had lower FA and higher mean diffusivity compared with controls in all major white matter tracts. The findings in this study may indicate that the associations between motor function and FA are caused by other tracts crossing the CST and CC, and/or by alterations in the periventricular white matter in the centrum semiovale. Some of the associations were in the opposite direction than hypothesized, thus higher FA does not always indicate better function. Furthermore, widespread white matter alterations in VLBW individuals persist into young adulthood.

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OBJECTIVE: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI. METHODS: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). RESULTS: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores. CONCLUSIONS: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.

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BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. METHODS: Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. RESULTS: 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. CONCLUSION: The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

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We sought to investigate white matter abnormalities in mild traumatic brain injury (mTBI) using diffusion-weighted magnetic resonance imaging (DW-MRI). We applied a global approach based on tract-based spatial statistics skeleton as well as constrained spherical deconvolution tractography. DW-MRI was performed on 102 patients with mTBI within two months post-injury and 30 control subjects. A robust global approach considering only the voxels with a single-fiber configuration was used in addition to global analysis of the tract skeleton and probabilistic whole-brain tractography. In addition, we assessed whether the microstructural parameters correlated with age, time from injury, patient's outcome and white matter MRI hyperintensities. We found that whole-brain global approach restricted to single-fiber voxels showed significantly decreased fractional anisotropy (FA) (p = 0.002) and increased radial diffusivity (p = 0.011) in patients with mTBI compared with controls. The results restricted to single-fiber voxels were more significant and reproducible than those with the complete tract skeleton or the whole-brain tractography. FA correlated with patient outcomes, white matter hyperintensities and age. No correlation was observed between FA and time of scan post-injury. In conclusion, the global approach could be a promising imaging biomarker to detect white matter abnormalities following traumatic brain injury.

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PURPOSE: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS. MATERIAL AND METHODS: Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains. RESULTS: ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = - 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05). CONCLUSIONS: The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.

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BACKGROUND: Cortical, thalamic and hippocampal gray matter atrophy in relapsing-remitting MS (RRMS) is associated cognitive deficits. However, the role of interconnecting white matter pathways including the fornix, cingulum, and uncinate fasciculus (UF) is less well studied. OBJECTIVE: To assess MS damage to a hippocampal-thalamic-prefrontal network and the relative contributions of its components to specific cognitive domains. METHODS: We calculated diffusion tensor fractional anisotropy (FA) in the fornix, cingulum and UF as well as thalamic and hippocampal volumes in 27 RRMS patients and 20 healthy controls. A neuropsychological battery was administered and 4 core tests known to be sensitive to MS changes were used to assess cognitive impairment. To determine the relationships between structure and cognition, all tests were grouped into 4 domains: attention/executive function, processing speed, verbal memory, and spatial memory. Univariate correlations with structural measures and depressive symptoms identified potential contributors to cognitive performance and subsequent linear regression determined their relative effects on performance in each domain. For significant predictors, we also explored the effects of laterality and axial versus radial diffusivity. RESULTS: RRMS patients had worse performance on the Symbol Digit Modalities Test, but no significant impairment in the 4 cognitive domains. RRMS had reduced mean FA of all 3 pathways and reduced thalamic and hippocampal volumes compared to controls. In RRMS we found that thalamic volume and BDI predicted attention/executive function, UF FA predicted processing speed, thalamic volume predicted verbal memory, and UF FA and BDI predicted spatial memory. CONCLUSIONS: Hippocampal-thalamic-prefrontal disruption affects cognitive performance in early RRMS with mild to minimal cognitive impairment, confirming both white and gray matter involvement in MS and demonstrating utility in assessing functional networks to monitor cognition.

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DTI studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression. In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration. DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (<1 year), moderate (1 up to 6 years) and long (6-10 years) disease duration periods. Statistical analyses of the fractional anisotropy (FA) data were performed using tract-based spatial statistics (TBSS). Whole-brain skeletal FA measurements showed a significant decrease between healthy controls and the short MS disease duration group, as well as between moderate disease duration and long disease duration groups, but failed to show a significant difference between short and moderate disease duration groups. Voxelwise analysis revealed clusters of diffuse FA reductions in 40 WM tracts when comparing healthy controls and MS short disease duration group, with the point of maximal significant difference located in the left inferior longitudinal fasciculus. Comparing short with long disease duration groups, progressive FA reduction was demonstrated across 30 WM tracts, with the point of maximal significant difference migrating to the body of the corpus callosum. A non-linear pattern of WM microstructure disruption occurs in RRMS. Alterations are seen early in the disease course within 1 year from onset, reach a plateau within the next 5 years, and only later additional WM changes are detected. An important period of a possible therapeutic window therefore exists within the early disease stage.

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Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and results in neurological and psychiatric (NP) symptoms in up to 40% of the patients. To date, the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) poses a challenge due to the lack of neuroradiological gold standards. In this study, we aimed to better localize and characterize normal appearing white matter (NAWM) changes in NPSLE by combining data from two quantitative MRI techniques, diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI). 9 active NPSLE patients (37 ± 13 years, all females), 9 SLE patients without NP symptoms (44 ± 11 years, all females), and 14 healthy controls (HC) (40 ± 9 years, all females) were included in the study. MTI, DTI and fluid attenuated inversion recovery (FLAIR) images were collected from all subjects on a 3 T MRI scanner. Magnetization transfer ratio (MTR), mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) maps and white matter lesion maps based on the FLAIR images were created for each subject. MTR and DTI data were then co-analyzed using tract-based spatial statistics and a cumulative lesion map to exclude lesions. Significantly lower MTR and FA and significantly higher AD, RD and MD were found in NPSLE compared to HC in NAWM regions. The differences in DTI measures and in MTR, however, were only moderately co-localized. Additionally, significant differences in DTI measures, but not in MTR, were found between NPSLE and SLE patients, suggesting that the underlying microstructural changes detected by MD are linked to the onset of NPSLE. The co-analysis of the anatomical distribution of MTI and DTI measures can potentially improve the diagnosis of NPSLE and contribute to the understanding of the underlying microstructural damage.

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Shwachman-Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman-Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9-19 years included in the Italian Shwachman-Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left limbic-anterior cingulate cortex (≥43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients show a thinner cortical thickness than that of controls (p = 0.01). Diffusion tensor imaging showed large, significant difference increases in both fractional anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract-based Spatial Statistics analysis identified six abnormal clusters of white matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto-parietal, right pontine, temporo-mesial and left anterior-medial-temporal regions. Brain areas activated during the Stroop task and those active during the resting state, are different, fewer and smaller in patients and correlate with worse performance (p = 0.002). Cognitive impairment in Shwachman-Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus).

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Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.

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PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25-70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients). METHODS: Applying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups. RESULTS: Statistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced. CONCLUSIONS: Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

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Depressive symptoms, even at a subclinical level, have been associated with structural brain abnormalities. However, previous studies have used regions of interest or small sample sizes, limiting the ability to generalize the results. In this study, we examined neuroanatomical structures of both gray matter and white matter associated with depressive symptoms across the whole brain in a large sample. A total of 810 community-dwelling adult participants underwent measurement of depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). The participants were not demented and had no neurological or psychiatric history. To examine the gray and white matter volume, we used structural MRI scans and voxel-based morphometry (VBM); to examine the white matter integrity, we used diffusion tensor imaging with tract-based spatial statistics (TBSS). In female participants, VBM revealed a negative correlation between bilateral anterior cingulate gray matter volume and the CES-D score. TBSS showed a CES-D-related decrease in fractional anisotropy and increase in radial and mean diffusivity in several white matter regions, including the right anterior cingulum. In male participants, there was no significant correlation between gray or white matter volume or white matter integrity and the CES-D score. Our results indicate that the reduction in gray matter volume and differences in white matter integrity in specific brain regions, including the anterior cingulate, are associated with depressive symptoms in women.

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

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INTRODUCTION: Huntington's disease (HD) is associated with progressive loss of caudate and white matter volume and integrity. Our aim was to systematically assess interactions between these changes and genetic markers of disease progression; we are not aware of previous studies in which this has been explicitly tested. METHODS: Tract-based spatial statistics were used to assess: (a) differences between the white matter diffusion metrics (fractional anisotropy and mean diffusivity) of 17 premanifest and 19 early manifest HD gene carriers and 21 controls, and (b) the relationships between diffusion metrics, caudate and total white matter volume, and disease burden score and CAG repeat length. Caudate and total white matter volumes were quantified using FIRST and SIENAX respectively. Multiple regression analysis was used to assess which of the imaging metrics predicted disease severity in the HD subjects. RESULTS: Diffusion metrics were significantly altered in premanifest and early HD gene carriers in comparison with controls throughout the white matter skeleton. Correlations between diffusion and volumetric metrics and disease progression were also present. Together, caudate volume and mean white matter fractional anisotropy and mean diffusivity predicted disease burden score in the HD subjects. CONCLUSIONS: The diffusion properties of white matter are extensively altered in HD, and are associated with markers of HD severity, and with caudate and white matter volumes. The correlation between diffusion metrics and white matter volume is stronger in HD subjects than in controls, but there is no such significant interaction for the correlation between diffusion and caudate volume: we propose that many of the changes in white matter diffusion in HD occur as a 'normal' physiological response to pathological caudate volume loss. We have defined the extent to which mean white matter fractional anisotropy, white matter volume and caudate volume are associated with disease burden score.

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Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome.

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Autism is a neurodevelopmental disorder in which white matter (WM) maturation is affected. We assessed WM integrity in 16 adolescents and 14 adults with high-functioning autism spectrum disorder (ASD) and in matched neurotypical controls (NT) using diffusion weighted imaging and Tract-based Spatial Statistics. Decreased fractional anisotropy (FA) was observed in adolescents with ASD in tracts involved in emotional face processing, language, and executive functioning, including the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculi. Remarkably, no differences in FA were observed between ASD and NT adults. We evaluated the effect of age on WM development across the entire age range. Positive correlations between FA values and age were observed in the right inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, the corpus callosum, and the cortical spinal tract of ASD participants, but not in NT participants. Our data underscore the dynamic nature of brain development in ASD, showing the presence of an atypical process of WM maturation, that appears to normalize over time and could be at the basis of behavioral improvements often observed in high-functioning autism.