Diffusion tensor imaging tractography and reliability analysis for limbic and paralimbic white matter tracts

Diffusion tensor imaging (DTI) provides the opportunity to study white matter tracts in vivo. The goal was to estimate the reliability of DTI tractography for the analysis of limbic and paralimbic white matter. Normative data from 24 healthy subjects and reliability data from four healthy and four depressed subjects were acquired at 1.5 Tesla, using twice-refocused spin-echo, echoplanar DTI and Fluid-Attenuated Inversion Recovery (FLAIR) DTI sequences. Fiber tracking was performed using the Fiber Assignment by Continuous Tracking algorithm. Fractional Anisotropy (FA), trace Apparent Diffusion Coefficient and tract volumes were calculated. The inter-rater (and intra-rater) intraclass correlation coefficients for FA values were as follows: rostral cingulum 0.89 (0.87), dorsal cingulum 0.85 (0.90), parahippocampal cingulum 0.85 (0.95), uncinate fasciculus 0.85 (0.87), medial prefrontal white matter 0.97 (0.99), ventromedial prefrontal white matter 0.92 (0.93), crus of fornix 0.80 (0.81). The reported DTI protocol provides a reliable method to analyze limbic and paralimbic white matter tracts relevant to psychiatric disorders.     

Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging

Magnetic resonance diffusion tensor imaging (DTI) was used to examine the integrity of midline white matter tracts in APPsw (Tg2576) transgenic mice, a mouse-model of cerebral amyloid deposition. Ex vivo DTI was performed on formalin-fixed brains from APPsw and age-matched transgene-negative control mice at the ages of 12, 15, and 17 months. The characteristics of water diffusion in six midline white matter tracts were quantified using four metrics: relative anisotropy (RA), mean diffusivity, axial diffusivity, and radial diffusivity. Two-way ANOVA analyses indicated a significant main effect of transgene on RA in the corpus callosum (CC) and ventral hippocampal commissure (VHC), due to small reductions (2-6%) in RA in APPsw mice relative to age-matched control mice. However, these reductions were not significant at any specific age group and were not progressive with increasing age. The other diffusion metrics exhibited no significant differences between APPsw and control mice in the CC and VHC, nor did any of the diffusion metrics exhibit significant differences between APPsw and control mice in other midline white matter tracts (anterior commissure, posterior commissure, fornix, and dorsal fornix). Overall, these results indicate that white matter integrity, as measured by ex vivo DTI, is predominately unaltered in formalin-fixed brains from amyloid plaque-bearing APPsw mice.     

Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment

Microstructural white matter deterioration is a frequent finding in mild cognitive impairment (MCI), potentially underlying default mode network (DMN) dysfunctioning. Thus far, microstructural damage in MCI has been attributed to Alzheimer's disease pathophysiology. A cerebrovascular role, in particular the role of cerebral small vessel disease (CSVD), received less interest. Here, we used diffusion tensor imaging (DTI) to examine the role of CSVD in microstructural deterioration within the normal appearing white matter (NAWM) in MCI. MCI patients were subdivided into those with (n = 20) and without (n = 31) macrostructural CSVD evidence on MRI. Using TBSS we performed microstructural integrity comparisons within the whole brain NAWM. Secondly, we segmented white matter tracts interconnecting DMN brain regions by means of automated tractography segmentation. We used NAWM DTI measures from these tracts as dependent variables in a stepwise‐linear regression analysis, with structural and demographical predictors. Our results indicated microstructural deterioration within the anterior corpus callosum, internal and external capsule and periventricular white matter in MCI patients with CSVD, while in MCI patients without CSVD, deterioration was restricted to the right perforant path, a tract along the hippocampus. Within the full cohort of MCI patients, microstructure within the NAWM of the DMN fiber tracts was affected by the presence of CSVD. Within the cingulum along the hippocampal cortex we found a relationship between microstructural integrity and ipsilateral hippocampal volume and the extent of white matter hyperintensity. In conclusion, we found evidence of CSVD‐related microstructural damage in fiber tracts subserving the DMN in MCI. Hum Brain Mapp 35:2836–2851, 2014. © 2013 Wiley Periodicals, Inc .     

DTI correlates of distinct cognitive impairments in Parkinson's disease

The spectrum of cognitive symptoms in Parkinson's disease (PD) can span various domains, including executive function, language, attention, memory, and visuospatial skills. These symptoms may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. The primary purpose of this study is to find microstructural correlates of impairments across these cognitive domains in PD using diffusion tensor imaging (DTI). Sixteen patients with PD with comprehensive neuropsychological evaluation and DTI data were retrospectively studied. Fractional anisotropy (FA) and mean diffusivity (MD) were assessed using regions‐of‐interest (ROI) analysis and confirmed with a voxel‐based approach. Executive function directly correlated with FA and inversely correlated with MD in mostly frontal white matter tracts, especially the anterior limb of the internal capsule and genu of the corpus callosum. Likewise, language and attentional performance demonstrated correlations with DTI parameters in the frontal regions, but the attention domain additionally recruited regions widespread throughout the brain, with the most significant correlation identified in cingulate gyrus (cingulum). Lastly, memory impairment mainly involved MD alterations within the fornix. No significant correlations were found between visuospatial skills and DTI measures. Despite some overlap, unique patterns of white matter diffusivity underlie impairments in distinct cognitive domains in patients with PD. DTI combined with neurocognitive tests may be a valuable biomarker for identifying cognitive impairments in PD. Hum Brain Mapp 35:1325–1333, 2014. © 2013 Wiley Periodicals, Inc.     

Fornix integrity and hippocampal volume in male schizophrenic patients.

BACKGROUND: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. METHODS: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (D(m)), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume. RESULTS: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes. CONCLUSIONS: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.     

Body mass index correlates negatively with white matter integrity in the fornix and corpus callosum: A diffusion tensor imaging study

Overweight or obese body habitus is associated with cognitive deficits, impaired brain function, gray matter atrophy, and white matter (WM) hyperintensities. However, few diffusion tensor imaging (DTI) studies have assessed WM integrity in relation to overweight or obese status. This study assessed relationships between body mass index (BMI) and values of DTI parameters among 51 normal weight (lean), overweight, and obese participants who were otherwise healthy. BMI correlated negatively with fractional anisotropy and axial eigenvalues (λ₁) in the body of corpus callosum (CC), positively with mean diffusivity and radial eigenvalues (λ_?) in the fornix and splenium of CC, and positively with λ₁ in the right corona radiata (CR) and superior longitudinal fasciculus (SLF). These data indicate that BMI correlates negatively with WM integrity in the fornix and CC. Furthermore, the different patterns of BMI‐related differences in DTI parameters at the fornix, body, and splenium of the CC, and the right CR and SLF suggest that different biological processes may underlie BMI‐related impairments of WM integrity in different brain regions. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Microstructural changes in white matter associated with freezing of gait in Parkinson's disease

In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing‐related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed‐based diffusion tensor imaging. Diffusion‐weighted images were collected in 26 PD patients and 16 age‐matched controls. Parkinson's disease groups with (n = 11) and without freezing of gait (n = 15) were matched for age and disease severity. We applied tract‐based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico‐cortical tracts. Tract‐based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico‐cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello‐pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non‐motor correlates of FOG. © 2015 International Parkinson and Movement Disorder Society     

Fornix integrity and hippocampal volume predict memory decline and progression to Alzheimer's disease

BackgroundThe fornix is the predominant outflow tract of the hippocampus, a brain region known to be affected early in the course of Alzheimer’s disease (AD). The aims of the present study were to: (1) examine the cross-sectional relationship between fornix diffusion tensor imaging (DTI) measurements (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity, and radial diffusivity), hippocampal volume, and memory performance, and (2) compare fornix DTI measures with hippocampal volumes as predictors of progression and transition from amnestic mild cognitive impairment to AD dementia.MethodsTwenty-three mild cognitive impairment participants for whom hippocampal volumetry and DTI were conducted at baseline received detailed evaluations at baseline; 3, 6, and 12 months; and 2.5 years. Six participants converted to AD over the follow-up period. Fornix and posterior cingulum DTI measurements and hippocampal volumes were ascertained using manual measures. Random effects models assessed each of the neuroimaging measures as predictors of decline on the Mini-Mental State Examination, Clinical Dementia Rating-sum of boxes, and memory z scores; receiver operating characteristic analyses examined the predictive value for conversion to AD.ResultsThere was a significant correlation between fornix FA and hippocampal volumes. However, only the fornix measurements (FA, MD, radial diffusivity, and axial diffusivity) were cross-sectionally correlated with memory z scores. Both fornix FA and hippocampal volumes were predictive of memory decline. Individually, fornix FA and MD and hippocampal volumes were very good predictors of progression, with likelihood ratios >83, and better than 90% accuracy.ConclusionFornix FA both cross-sectionally correlated with and longitudinally predicted memory decline and progression to AD. Manually drawn region of interest within the fornix shows promise comparable with hippocampal volume as a predictive biomarker of progression, and this finding warrants replication in a larger study.     

Heritability of white matter microstructure in late middle age: A twin study of tract‐based fractional anisotropy and absolute diffusivity indices

There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle‐aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56–66 years old. Using an atlas‐based registration approach to delineate individual white matter tracts, we investigated mean DTI‐based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%–80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community‐based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026–2036, 2017. © 2017 Wiley Periodicals, Inc.     

Regional networks underlying interhemispheric connectivity: an EEG and DTI study in healthy ageing and amnestic mild cognitive impairment

Interhemispheric coherence derived from electroencephalogram (EEG) recordings is a measure of functional interhemispheric connectivity. Diffusion tensor imaging (DTI) determines the integrity of subcortical fiber tracts. We studied the pattern of subcortical fiber tracts underlying interhemispheric coherence and its alteration in 16 subjects with amnestic mild cognitive impairment (MCI), an at risk syndrome for Alzheimer's disease, and 20 cognitively healthy elderly control subjects using resting state EEG and high resolution DTI at 3 T. We used a multivariate network approach based on principal component analysis to determine effects of coherence on the regional pattern of diffusivity. Temporo-parietal coherence in the alpha band was significantly correlated with diffusivity in predominantly posterior white matter tracts including posterior corpus callosum, parietal, temporal and occipital lobe white matter, thalamus, midbrain, pons, and cerebellum, both in MCI subjects and controls (P < 0.05). In MCI subjects, frontal coherence in the alpha band was significantly correlated with a predominately frontal pattern of diffusivity including fiber tracts of the anterior corpus callosum, frontal lobe white matter, thalamus, pons, and cerebellum (P < 0.05). The study provides a methodology to access specific networks of subcortical fiber tracts subserving the maintenance of interhemispheric resting state coherence in the human brain.     

White matter integrity correlates with residual consciousness in patients with severe brain injury

Previous studies have suggested that white matter disruption plays an important role in disorders of consciousness (DOC) after severe brain injury. Nevertheless, the integrity of white matter architecture supporting consciousness and its relations with clinical severity in patients with DOC remain to be established. In this study, diffusion tensor imaging (DTI) data was collected from 14 DOC patients and 15 healthy control subjects. We combined tract-based spatial statistics (TBSS) with region of interest (ROI) analysis to examine differences of DTI metrics on white matter skeletons between DOC patients and healthy controls, and the association between white matter integrity and patients’ residual consciousness assessed by Coma Recovery Scale-Revised (CRS-R). We found that: (1) patients with DOC had widespread white matter integrity disruptions, especially in the fornix; (2) the alteration of white matter microstructure was mainly attributed to the increase in radial diffusivity, possibly reflecting demyelination; (3) the behavioral CRS-R assessment score was positively correlated with white matter integrity in the fornix, uncinate fasciculus, pontine crossing tract, and posterior limb of internal capsule. Our results suggest that despite the widespread abnormalities of white matter following severe brain injury, the impairment of consciousness is likely to result from disruptions of key pathways that link brain regions in distributed networks.     

Rostral brain axonal injury in congenital central hypoventilation syndrome

Brain injury underlying the state‐related loss of ventilatory drive, autonomic, cognitive, and affective deficits in congenital central hypoventilation syndrome (CCHS) patients appears throughout the brain, as demonstrated by magnetic resonance (MR) T2 relaxometry and mean diffusivity studies. However, neither MR measure is optimal to describe types of axonal injury essential for assessing neural interactions responsible for CCHS characteristics. To evaluate axonal integrity and partition the nature of tissue damage (axonal vs. myelin injury) in CCHS, we measured water diffusion parallel (axial diffusivity) and perpendicular (radial diffusivity) to rostral brain fibers, indicative of axonal and myelin changes, respectively, with diffusion tensor imaging (DTI). We performed DTI in 12 CCHS (age 18.5 ± 4.9 years, 7 male) and 30 control (17.7 ± 4.6 years, 18 male) subjects, using a 3.0‐Tesla MR imaging scanner. Axial and radial diffusivity maps were calculated, spatially normalized, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). Significantly increased radial diffusivity, primarily indicative of myelin injury, emerged in fibers of the corona radiata, internal capsule, corpus callosum, hippocampus through the fornix, cingulum bundle, and temporal and parietal lobes. Increased axial diffusivity, suggestive of axonal injury, appeared in fibers of the internal capsule, thalamus, corona radiata, and occipital and temporal lobes. Multiple brain regions showed both higher axial and radial diffusivity, indicative of loss of tissue integrity with a combination of myelin and axonal injury, including basal ganglia, bed nucleus, and limbic, occipital, and temporal areas. The processes underlying injury are unclear, but likely stem from both hypoxic and developmental processes. © 2010 Wiley‐Liss, Inc.     

Extrahippocampal gray matter loss and hippocampal deafferentation in patients with temporal lobe epilepsy

Purpose: Medial temporal epilepsy (MTLE) is associated with extrahippocampal brain atrophy. The mechanisms underlying brain damage in MTLE are unknown. Seizures may lead to neuronal damage, but another possible explanation is deafferentation from loss of hippocampal connections. This study aimed to investigate the relationship between hippocampal deafferentation and brain atrophy in MTLE. Methods: Three different MRI studies were performed involving 23 patients with unilateral MTLE (8 left and 15 right) and 34 healthy controls: (1) voxel‐based morphometry (VBM), (2) diffusion tensor imaging (DTI) and (3) probabilistic tractography (PT). VBM was employed to define differences in regional gray matter volume (GMV) between controls and patients. Voxel‐wise analyses of DTI evaluated differences in fractional anisotropy (FA), mean diffusivity (MD) and hippocampal PT. Z‐scores were computed for regions‐of‐interest (ROI) GMV and peri‐hippocampal FA and MD (to quantify hippocampal fiber integrity). The relationship between hippocampal deafferentation and regional GMV was investigated through the association between ROI Z scores and hippocampal fiber integrity. Results: Patients with MTLE exhibited a significant reduction in GMV and FA in perihippocampal and limbic areas. There was a decrease in hippocampal PT in patients with MTLE in limbic areas. A significant relationship between loss of hippocampal connections and regional GMV atrophy was found involving the putamen, pallidum, middle and inferior temporal areas, amygdala and ceberellar hemisphere. Discussion: There is a relationship between hippocampal disconnection and regional brain atrophy in MTLE. These results indicate that hippocampal deafferentation plays a contributory role in extrahippocampal brain damage in MTLE.     

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white‐matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school‐aged dyslexic children with 33 age‐matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto‐occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well‐recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. Hum Brain Mapp 37:1443‐1458, 2016. © 2016 Wiley Periodicals, Inc.     

Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer's disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.     

Early changes in white matter pathways of the sensorimotor cortex in premanifest Huntington's disease

Objectives: To investigate the function–structure relationship of white matter within different stages of Huntington's disease (HD) using diffusion tensor imaging (DTI). Experimental design: From the TRACK‐HD study, an early stage HD group and a premanifest gene carrier group (PMGC) were age‐matched to two healthy control groups; all underwent 3‐T MRI scanning of the brain. Region of interest (ROI) segmentation of the corpus callosum, caudate nucleus, thalamus, prefrontal cortex, and sensorimotor cortex was applied, and the apparent fiber pathways of these regions were analyzed. Functional measures of motor, oculomotor, cognition, and behavior were correlated to DTI measures. Principle observations: In PMGC versus controls, higher apparent diffusion coefficient (ADC) was seen in white matter pathways of the sensorimotor cortex (P < 0.01) and in the ROI of corpus callosum (P < 0.017). In early HD, fiber tract analysis showed higher ADC in pathways of the corpus callosum, thalamus, sensorimotor, and prefrontal region (P < 0.01). ROI analysis showed higher diffusivity in the corpus callosum and caudate nucleus (P < 0.017). Motor, oculomotor, cognition, and probability of onset within 2 and 5 years, correlated well with ADC measures of the corpus callosum (P < 0.01 – P < 0.005), sensorimotor (P < 0.01 – P < 0.005), and prefrontal region (P < 0.01). Conclusions: Disturbances in the white matter connections of the sensorimotor cortex can be demonstrated not only in manifest HD but also in premanifest gene carriers. Connectivity measures are well related to clinical functioning. DTI measures can be regarded as a potential biomarker for HD, due to their ability to objectify changes in brain structures and their role within brain networks. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Cerebral white matter abnormalities in patients with charcot‐marie‐tooth disease

Here, we report the structural evidence of cerebral white matter abnormalities in Charcot‐Marie‐Tooth (CMT) patients and the relationship between these abnormalities and clinical disability. Brain diffusion tensor imaging (DTI) was performed in CMT patients with demyelinating (CMT1A/CMT1E), axonal (CMT2A/CMT2E), or intermediate (CMTX1/DI‐CMT) peripheral neuropathy. Although all patients had normal brain magnetic resonance imaging, all genetic subgroups except CMT1A had abnormal DTI findings indicative of significant cerebral white matter abnormalities: decreased fractional anisotropy and axial diffusivity, and increased radial diffusivity. DTI abnormalities were correlated with clinical disability, suggesting that there is comorbidity of central nervous system damage with peripheral neuropathy in CMT patients. ANN NEUROL 2017;81:147–151     

In vivo demonstration of microstructural brain pathology in progressive supranuclear palsy: A DTI study using TBSS

We investigated DTI changes, potentially indicating alterations of microstructure and brain tissue integrity in 13 patients with probable progressive supranuclear palsy (PSP, Richardson syndrome) at stage III or less and 10 age‐matched controls using a whole brain analysis of diffusion tensor imaging (DTI) data. DTI images were analyzed using tract‐based spatial statistics, a hypothesis‐free technique. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were determined. In patients with PSP, significant increases in FA (P < 0.0001), an unspecific measure of microstructural tissue integrity, were found in the cerebellum and in the superior cerebellar peduncle bilaterally, in the fornix, the body of the corpus callosum and the olfactory region, when compared with age‐matched healthy controls. Further, regional reductions in AD (P < 0.0001), an indicator of altered axonal integrity, were observed in the pons, the right substantia nigra and the cerebellar white matter bilaterally. Significant increases in RD (P < 0.0001), a potential measure of altered myelin integrity, occurred bilaterally in the superior cerebellar peduncle, the cerebellar white matter, the vermis of the cerebellum, the fornix, the body of the corpus callosum, and the olfactory region. RD values in the superior cerebellar peduncle discriminated patients with PSP and controls with high sensitivity (0.92) and specificity (1.0). The findings are supported by neuropathological studies. Our data suggest the usefulness of this clinically available new technique as a possible tool for differential diagnosis. © 2010 Movement Disorder Society     

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis

In a multicenter setting, we applied voxel‐based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal‐appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing‐remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel‐wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty‐three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive‐relevant WM tracts followed by atrophy of cognitive‐relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel‐wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. Hum Brain Mapp 37:1627‐1644, 2016. © 2016 Wiley Periodicals, Inc.     

Structural and diffusion tensor imaging of the fornix in childhood- and adolescent-onset schizophrenia

ObjectiveThere is emerging evidence that aberrations in the integrity of cerebral white matter tracts, especially those connected to limbic structures, play a role in the pathophysiology of schizophrenia. The fornix is the primary efferent neural pathway of the hippocampus and has been shown to be abnormal in adults with schizophrenia.MethodHigh-resolution structural magnetic resonance imaging and diffusion tensor images were obtained on 15 patients with childhood- and adolescent-onset schizophrenia and 15 age- and sex-matched controls. Measures of cross-sectional area and water diffusion properties were obtained on regions of interest of the fornix performed by a trained radiologist.ResultsThe volume of the fornix was significantly smaller (10.9%) in children and adolescents with schizophrenia compared to controls (Cohen d = 0.87, p = .025). There were no significant differences between the fractional anisotropy or mean diffusivity between the groups.ConclusionsThese findings suggest that the early stages of schizophrenia are associated with a decrease in fornix volume without microstructural white matter changes. The volume differences may reflect an early insult to neighboring brain regions (i.e., hippocampus), that could decrease the number of efferent fibers without necessarily disrupting fiber integrity. J. Am. Acad. Child Adolesc. Psychiatry, 2008; 47(7):826–832.