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Background: Becker muscular dystrophy (BMD) is an X-linked disorder characterized by slow, progressive muscle damage and muscle weakness. Hallmarks include fibre-size variation and replacement of skeletal muscle with fibrous and adipose tissues, after repeated cycles of regeneration. Muscle histology can detect these features, but the required biopsies are invasive, are difficult to repeat and capture only small muscle volumes. Diffusion-tensor magnetic resonance imaging (DT-MRI) is a potential non-invasive alternative that can calculate muscle fibre diameters when applied with the novel random permeable barrier model (RPBM). In this study, we assessed muscle fibre diameters using DT-MRI in BMD patients and healthy controls and compared these with histology. Methods: We included 13 BMD patients and 9 age-matched controls, who underwent water-fat MRI and DT-MRI at multiple diffusion times, allowing RPBM parameter estimation in the lower leg muscles. Tibialis anterior muscle biopsies were taken from the contralateral leg in 6 BMD patients who underwent DT-MRI and from an additional 32 BMD patients and 15 healthy controls. Laminin and Sirius-red stainings were performed to evaluate muscle fibre morphology and fibrosis. Twelve ambulant patients from the MRI cohort underwent the North Star ambulatory assessment, and 6-min walk, rise-from-floor and 10-m run/walk functional tests. Results: RPBM fibre diameter was significantly larger in BMD patients (P = 0.015): mean (SD) = 68.0 (25.3) μm versus 59.4 (19.2) μm in controls. Inter-muscle differences were also observed (P ≤ 0.002). Both inter- and intra-individual RPBM fibre diameter variability were similar between groups. Laminin staining agreed with the RPBM, showing larger median fibre diameters in patients than in controls: 72.5 (7.9) versus 63.2 (6.9) μm, P = 0.006. However, despite showing similar inter-individual variation, patients showed more intra-individual fibre diameter variability than controls—mean variance (SD) = 34.2 (7.9) versus 21.4 (6.9) μm, P

Несмотря на эффективную гипотензивную терапию, глаукомная оптическая нейропатия нередко прогрессирует. Возможный патогенетический механизм этой прогрессии – нейродегенерация, объединяющая многие инволюционные заболевания такие, как болезнь Альцгеймера, болезнь Паркинсона и другие. Несмотря на разную этиологию и клиническую картину, всех их объединяет несколько общих признаков, характерных для инволюционных заболеваний: увеличение заболеваемости с возрастом, практически бессимптомное начало и прогрессирующее ухудшение функций, генетическая предрасположенность. Гибель нейронов при всех нейродегенеративных заболеваниях (в том числе и глаукоме) осуществляется по механизму апоптоза, в основе которого лежат следующие патологические процессы: депривация нейротрофических факторов, повышение концентрации возбуждающих аминокислот, окислительный стресс и нейровоспаление. В данном обзоре представлены современные данные об аксональной и транссинаптической нейродегенерации, об оксидативном стрессе и глутаматной эксайтоксичности при глаукоме как ведущих звеньях в распространении патологического процесса и основных мишенях для нейропротекторной терапии., Glaucomatous optic neuropathy in some cases is known to progress despite effective hypotensive therapy. It might be explained by an underlying pathogenic mechanism of neurodegeneration that unites multiple involution-related diseases, such as Alzheimer's, Parkinson's and others. Despite differing etiology and clinical picture, they are all united by several common features characteristic of involution-related diseases: age-related morbidity increase, general lack of symptoms at the onset, progressive function deterioration and genetic predisposition. Neuron death in all degenerative diseases including glaucoma follows a common apoptosis mechanism, characterized by the following underlying mechanisms: neurotrophic factor deprivation, excitatory amino acids level increase, oxidative stress and neuroinflammation. This review presents current data on axonal and transsynaptic neurodegeneration, oxidative stress and glutamate exitotoxicity as leading components of the pathological glaucoma process and main targets of neuroprotective therapy., №3 (2018)

Purpose Diffusion tensor cardiovascular magnetic resonance (DT-CMR) has a limited spatial resolution. The purpose of this study was to demonstrate high-resolution DT-CMR using a segmented variable density spiral sequence with correction for motion, off-resonance, and T2*-related blurring. Methods A single-shot stimulated echo acquisition mode (STEAM) echo-planar-imaging (EPI) DT-CMR sequence at 2.8 × 2.8 × 8 mm3 and 1.8 × 1.8 × 8 mm3 was compared to a single-shot spiral at 2.8 × 2.8 × 8 mm3 and an interleaved spiral sequence at 1.8 × 1.8 × 8 mm3 resolution in 10 healthy volunteers at peak systole and diastasis. Motion-induced phase was corrected using the densely sampled central k-space data of the spirals. STEAM field maps and T2* measures were obtained using a pair of stimulated echoes each with a double spiral readout, the first used to correct the motion-induced phase of the second. Results The high-resolution spiral sequence produced similar DT-CMR results and quality measures to the standard-resolution sequence in both cardiac phases. Residual differences in fractional anisotropy and helix angle gradient between the resolutions could be attributed to spatial resolution and/or signal-to-noise ratio. Data quality increased after both motion-induced phase correction and off-resonance correction, and sharpness increased after T2* correction. The high-resolution EPI sequence failed to provide sufficient data quality for DT-CMR reconstruction. Conclusion In this study, an in vivo DT-CMR acquisition at 1.8 × 1.8 mm2 in-plane resolution was demonstrated using a segmented spiral STEAM sequence. Motion-induced phase and off-resonance corrections are essential for high-resolution spiral DT-CMR. Segmented variable density spiral STEAM was found to be the optimal method for acquiring high-resolution DT-CMR data.

The right planum temporale region is typically involved in higher-order auditory processing. After deafness, this area reorganizes to become sensitive to visual motion. This plasticity is thought to support compensatory enhancements to visual ability. In earlier work we showed that enhanced visual motion detection abilities in early-deaf people correlate with cortical thickness in a subregion of the right planum temporale. In the current study, we build on this earlier result by examining the relationship between enhanced visual motion detection ability and white matter structure in this area in the same sample. We used diffusion-weighted magnetic resonance imaging and extracted the measures of white matter structure from a region-of-interest just below the grey matter surface where cortical thickness correlates with visual motion detection ability. We also tested control regions-of-interest in the auditory and visual cortices where we did not expect to find a relationship between visual motion detection ability and white matter. We found that in the right planum temporale subregion, and in no other tested regions, fractional anisotropy, radial diffusivity, and mean diffusivity correlated with visual motion detection thresholds. We interpret this change as further evidence of a structural correlate of cross modal reorganization after deafness. (C) 2016 Elsevier B.V. All rights reserved.

Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5 months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease., Highlights • We analyzed the microstructural changes in rTg4510 and wild type mice at 8.5 months. • We correlated microstructural findings with histological measures of tau burden • We compare two diffusion MR models: DTI and NODDI. • Both models revealed changes in tissue microstructure due to tau pathology. • The NODDI metrics demonstrated a good correlation with histological measures of tau burden.

Advanced age is associated with declines in brain structure and in cognitive performance, but it is unclear which aspects of brain aging mediate cognitive declines. We inquired if individual differences in white matter integrity contribute to age differences in two cognitive domains with established vulnerability to aging: executive functioning and speed of processing. The participants were healthy volunteers aged 50-81, some of whom had elevated blood pressure, a known vascular risk factor. Using latent variable analyses, we examined whether age differences in regional white matter integrity mediated age-related differences in executive functions and speed of processing. Although diffusion-related latent variables showed stronger age differences than white matter volumes and white matter hyperintensity volumes, only one of them was significantly associated with cognitive performance. Smaller linear anisotropy partially mediated age-related reduction in speed of processing. The effect was significant in posterior (temporal-parietal-occipital) but not anterior (frontal) region, and appeared stronger for cognitive rather than reaction time measures of processing speed. The presence of hypertensive participants did not affect the results. We conclude that in healthy adults, deterioration of axonal integrity and ensuing breech of connectivity may underpin age-related slowing of information processing. (C) 2011 Elsevier Inc. All rights reserved.

International audience; We present a visualization technique for brain fiber tracts from DTI data that provides insight into the structure of white matter through visual abstraction. We achieve this abstraction by analyzing the local similarity of tract segment directions at different scales using a stepwise increase of the search range. Next, locally similar tract segments are moved toward each other in an iterative process, resulting in a local contraction of tracts perpendicular to the local tract direction at a given scale. This not only leads to the abstraction of the global structure of the white matter as represented by the tracts, but also creates volumetric voids. This increase of empty space decreases the mutual occlusion of tracts and, consequently, results in a better understanding of the brain's three-dimensional fiber tract structure. Our implementation supports an interactive and continuous transition between the original and the abstracted representations via various scale levels of similarity. We also support the selection of groups of tracts, which are highlighted and rendered with the abstracted visualization as context.

White matter tracts mature asymmetrically during development, and this development can be studied using diffusion magnetic resonance imaging. The aims of this study were i. to generate dynamic population-averaged white matter registration templates covering in detail the period from 25 weeks gestational age to term, and extending to 2 years of age based on DTI and fractional anisotropy, ii. to produce tract-specific probability maps of the corticospinal tracts, forceps major and forceps minor using probabilistic tractography, and iii. to assess the development of these tracts throughout this critical period of neurodevelopment. We found evidence for asymmetric development across the fiber bundles studied, with the corticospinal tracts showing earlier maturation (as measured by fractional anisotropy) but slower volumetric growth compared to the callosal fibers. We also found evidence for an anterior to posterior gradient in white matter microstructure development (as measured by mean diffusivity) in the callosal fibers, with the posterior forceps major developing at a faster rate than the anterior forceps minor in this age range. Finally, we report a protocol for delineating callosal and corticospinal fibers in extremely premature cohorts, and make available population-averaged registration templates and a probabilistic tract atlas which we hope will be useful for future neonatal and infant white-matter imaging studies.

Diffusion-weighted (DW) magnetic resonance imaging (MRI) is a non-invasive imaging method, which can be used to investigate neural tracts in the white matter (WM) of the brain. Significant partial volume effects (PVEs) are present in the DVV signal due to relatively large voxel sizes. These PVEs can be caused by both non-WM tissue, such as gray matter (GM) and cerebrospinal fluid (CSF), and by multiple non-parallel WM fiber populations. High angular resolution diffusion imaging (HARDI) methods have been developed to correctly characterize complex WM fiber configurations, but to date, many of the HARDI methods do not account for non-WM PVEs. In this work, we investigated the isotropic PVEs caused by non-WM tissue in WM voxels on fiber orientations extracted with constrained spherical deconvolution (CSD). Experiments were performed on simulated and real DW-MRI data. In particular, simulations were performed to demonstrate the effects of varying the diffusion weightings, signal-to-noise ratios (SNRs), fiber configurations, and tissue fractions. Our results show that the presence of non-WM tissue signal causes a decrease in the precision of the detected fiber orientations and an increase in the detection of false peaks in CSD. We estimated 35-50% of WM voxels to be affected by non-WM PVEs. For HARDI sequences, which typically have a relatively high degree of diffusion weighting, these adverse effects are most pronounced in voxels with GM PVEs. The non-WM PVEs become severe with 50% GM volume for maximum spherical harmonics orders of 8 and below, and already with 25% GM volume for higher orders. In addition, a low diffusion weighting or SNR increases the effects. The non-WM PVEs may cause problems in connectomics, where reliable fiber tracking at the WM G M interface is especially important. We suggest acquiring data with high diffusion-weighting 2500-3000 s/mm(2), reasonable SNR (similar to 30) and using lower SH orders in GM contaminated regions to minimize the non-WM PVEs in CSD.

Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age- and gender-matched healthy controls using a 64 gradient direction sequence, (b = 1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

International audience; The exact anatomical localization of right hemisphere lesions that lead to left spatial neglect is still debated. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects, and lesion size may account for conflicting results that have been reported in the literature. Here, we present a comprehensive anatomical investigation of the gray- and white matter lesion correlates of left spatial neglect, which was run in a sample 58 patients with subacute or chronic vascular strokes in the territory of the right middle cerebral artery. Standard voxel-based correlates confirmed the role played by lesions in the posterior parietal cortex (supramarginal gyrus, angular gyrus, and temporal-parietal junction), in the frontal cortex (frontal eye field, middle and inferior frontal gyrus), and in the underlying parietal-frontal white matter. Using a new diffusion tensor imaging-based atlas of the human brain, we were able to run, for the first time, a detailed analysis of the lesion involvement of subcortical white matter pathways. The results of this analysis revealed that, among the different pathways linking parietal with frontal areas, damage to the second branch of the superior longitudinal fasciculus (SLF II) was the best predictor of left spatial neglect. The group study also revealed a subsample of patients with neglect due to focal lesion in the lateral-dorsal portion of the thalamus, which connects the premotor cortex with the inferior parietal lobule. The relevance of fronto-parietal disconnection was further supported by complete in vivo tractography dissection of white matter pathways in 2 patients, one with and the other without signs of neglect. These 2 patients were studied both in the acute phase and 1 year after stroke and were perfectly matched for age, handedness, stroke onset, lesion size, and for cortical lesion involvement. Taken together, the results of the present study support the hypothesis that anatomical disconnections leading to a functional breakdown of parietal-frontal networks are an important pathophysiological factor leading to chronic left spatial neglect. Here, we propose that different loci of SLF disconnection on the rostro-caudal axis can also be associated with disconnection of short-range white matter pathways within the frontal or parietal areas. Such different local disconnection patterns can play a role in the important clinical variability of the neglect syndrome.