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Multiple sclerosis features complex pathological changes in gray matter that begin early and eventually lead to diffuse atrophy. Novel approaches to image gray matter microstructural alterations in-vivo are highly sought after and would enable more sensitive monitoring of disease activity and progression. This cross-sectional study aimed to assess the sensitivity of high-gradient diffusion MRI for microstructural tissue damage in cortical and deep gray matter in people with multiple sclerosis and test the hypothesis that reduced cortical cell body density is associated with cortical and deep gray matter volume loss. Forty-one people with multiple sclerosis (ages 24–72, 14 females) and 37 age- and sex-matched healthy controls were scanned on a 3 Tesla Connectom MRI scanner equipped with 300 mT/m gradients using a multi-shell diffusion MRI protocol. The soma and neurite density imaging model was fitted to high-gradient diffusion MRI data to obtain estimates of intra-neurite, intra-cellular, and extra-cellular signal fractions and apparent soma radius. Cortical and deep gray matter microstructural imaging metrics were compared between multiple sclerosis and healthy controls and correlated with gray matter volume, clinical disability and cognitive outcomes. People with multiple sclerosis showed significant cortical and deep gray matter volume loss compared to healthy controls. People with multiple sclerosis showed trends toward lower cortical intra-cellular signal fraction and significantly lower intra-cellular and higher extra-cellular signal fractions in deep gray matter, especially the thalamus and caudate, compared to healthy controls. Changes were most pronounced in progressive disease and correlated with the Expanded Disability Status Scale, but not the Symbol Digit Modalities Test. In multiple sclerosis, normalized thalamic volume was associated with thalamic microstructural imaging metrics. Whereas thalamic volume loss did not correlate with cortical volume loss, cortical microstructural imaging metrics were significantly associated with thalamic volume, and not with cortical volume. Compared to the short diffusion time (Δ=19 ms) achievable on the Connectom scanner, at the longer diffusion time of Δ=49 ms attainable on clinical scanners, multiple sclerosis-related changes in imaging metrics were generally less apparent with lower effect sizes in cortical and deep gray matter. Soma and neurite density imaging metrics obtained from high-gradient diffusion MRI data provide detailed gray matter characterization beyond cortical and thalamic volumes and distinguish multiple sclerosis-related microstructural pathology from healthy controls. Cortical cell body density correlates with thalamic volume, appears sensitive to the microstructural substrate of neurodegeneration and reflects disability status in people with multiple sclerosis, becoming more pronounced as disability worsens.

Axonal damage in the corpus callosum is prevalent in multiple sclerosis (MS). Although callosal damage is associated with disrupted functional connectivity between hemispheres, it is unclear how this relates to cognitive and physical disability. We investigated this phenomenon using advanced measures of microstructural integrity in the corpus callosum and surface-based Homologous Inter-hemispheric Connectivity (sHIC) in the cortex. We found that sHIC was significantly decreased in primary motor, somatosensory, visual, and temporal cortical areas in a group of 36 participants with MS (29 relapsing-remitting, 4 secondary progressive MS, and 3 primary progressive MS) compared with 42 healthy controls (cluster level, p

Objective To evaluate alterations in apparent axon diameter and axon density obtained by high‐gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. Methods Thirty people with MS (23 relapsing‐remitting MS [RRMS], 7 progressive MS [PMS]) and 23 healthy controls were scanned on a human 3‐tesla (3T) MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Data were fitted to a three‐compartment geometric model of white matter to estimate apparent axon diameter and axon density in the midline corpus callosum. Neurologic disability and cognitive function were measured using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Minimal Assessment of Cognitive Function in MS battery. Results Apparent axon diameter was significantly larger and axon density reduced in the normal‐appearing corpus callosum (NACC) of MS patients compared to healthy controls, with similar trends seen in PMS compared to RRMS. Larger apparent axon diameter in the NACC of MS patients correlated with greater disability as measured by the EDSS (r = 0.555, P = 0.007) and poorer performance on the Symbol Digits Modalities Test (r = ‐0.593, P = 0.008) and Brief Visuospatial Memory Test–Revised (r = −0.632, P

Strong gradient systems can improve the signal-to-noise ratio of diffusion MRI measurements and enable a wider range of acquisition parameters that are beneficial for microstructural imaging. We present a comprehensive diffusion MRI dataset of 26 healthy participants acquired on the MGH-USC 3 T Connectome scanner equipped with 300 mT/m maximum gradient strength and a custom-built 64-channel head coil. For each participant, the one-hour long acquisition systematically sampled the accessible diffusion measurement space, including two diffusion times (19 and 49 ms), eight gradient strengths linearly spaced between 30 mT/m and 290 mT/m for each diffusion time, and 32 or 64 uniformly distributed directions. The diffusion MRI data were preprocessed to correct for gradient nonlinearity, eddy currents, and susceptibility induced distortions. In addition, scan/rescan data from a subset of seven individuals were also acquired and provided. The MGH Connectome Diffusion Microstructure Dataset (CDMD) may serve as a test bed for the development of new data analysis methods, such as fiber orientation estimation, tractography and microstructural modelling., Measurement(s)brain measurementTechnology Type(s)diffusion magnetic resonance imagingFactor Type(s)diffusion time • gradient strength • directionSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.16910290

In multiple sclerosis, individual lesion-type patterns on magnetic resonance imaging might be valuable for predicting clinical outcome and monitoring treatment effects. Neuropathological and imaging studies consistently show that cortical lesions contribute to disease progression. The presence of chronic active white matter lesions harbouring a paramagnetic rim on susceptibility-weighted magnetic resonance imaging has also been associated with an aggressive form of multiple sclerosis. It is, however, still uncertain how these two types of lesions relate to each other, or which one plays a greater role in disability progression. In this prospective, longitudinal study in 100 multiple sclerosis patients (74 relapsing-remitting, 26 secondary progressive), we used ultra-high field 7-T susceptibility imaging to characterize cortical and rim lesion presence and evolution. Clinical evaluations were obtained over a mean period of 3.2 years in 71 patients, 46 of which had a follow-up magnetic resonance imaging. At baseline, cortical and rim lesions were identified in 96% and 63% of patients, respectively. Rim lesion prevalence was similar across disease stages. Patients with rim lesions had higher cortical and overall white matter lesion load than subjects without rim lesions (P = 0.018–0.05). Altogether, cortical lesions increased by both count and volume (P = 0.004) over time, while rim lesions expanded their volume (P = 0.023) whilst lacking new rim lesions; rimless white matter lesions increased their count but decreased their volume (P = 0.016). We used a modern machine learning algorithm based on extreme gradient boosting techniques to assess the cumulative power as well as the individual importance of cortical and rim lesion types in predicting disease stage and disability progression, alongside with more traditional imaging markers. The most influential imaging features that discriminated between multiple sclerosis stages (area under the curve±standard deviation = 0.82 ± 0.08) included, as expected, the normalized white matter and thalamic volume, white matter lesion volume, but also leukocortical lesion volume. Subarachnoid cerebrospinal fluid and leukocortical lesion volumes, along with rim lesion volume were the most important predictors of Expanded Disability Status Scale progression (area under the curve±standard deviation = 0.69 ± 0.12). Taken together, these results indicate that while cortical lesions are extremely frequent in multiple sclerosis, rim lesion development occurs only in a subset of patients. Both, however, persist over time and relate to disease progression. Their combined assessment is needed to improve the ability of identifying multiple sclerosis patients at risk of progressing disease., The study by Treaba et al. investigates the contribution of cortical and susceptibility rim lesions at 7-T on disease burden and progression in multiple sclerosis using modern machine learning algorithms. While longitudinal lesion accumulation predominates for the cortical over the rim lesion type, both types are associated with disability progression., Graphical Abstract Graphical Abstract

Highlights • Optic radiation (OR) white matter damage is associated with retinal thinning in MS. • Axonal water fraction (AWF) reflects axonal damage in the OR of MS patients. • AWF in the OR shows a tract-specific association with retinal thinning., Introduction White matter damage in the visual pathway is common in multiple sclerosis (MS) and is associated with retinal thinning, although the underlying mechanism of association remains unclear. The goal of this work was to evaluate the presence and extent of white matter tract integrity (WMTI) alterations in the optic radiation (OR) in people with MS and to investigate the association between WMTI metrics and retinal thinning in the eyes of MS patients without a history of optic neuritis (ON) as measured by optical coherence tomography (OCT). We hypothesized that WMTI metrics would reflect axonal damage that occurs in the OR in MS, and that axonal alterations revealed by WMTI would be associated with retinal thinning. Methods Twenty-nine MS patients without previous ON in at least one eye and twenty-nine age-matched healthy controls (HC) were scanned on a dedicated high-gradient 3-Tesla MRI scanner with 300 mT/m maximum gradient strength using a multi-shell diffusion MRI protocol (b = 800, 1500, 2400 s/mm2). The patients were divided into two subgroups according to history without ON (N = 18) or with ON in one eye (N = 11). Diffusion tensor imaging (DTI) metrics and WMTI metrics derived from diffusion kurtosis imaging were assessed in normal-appearing white matter (NAWM) of the OR and in focal lesions. Retinal thickness in the eyes of MS patients was measured by OCT. Student’s t-test was used to assess group differences between MRI metrics. Linear regression was used to study the relationship between OCT metrics, including retinal nerve fiber layer (RNFL) and combined ganglion cell and inner plexiform layer thickness (GCL/IPL), visual acuity measures and DTI and WMTI metrics. Results OR NAWM in MS showed significantly decreased axonal water fraction (AWF) compared to HC (0.36 vs 0.39, p

BACKGROUND AND PURPOSE: Remyelination represents an area of great therapeutic interest in multiple sclerosis but currently lacks a robust imaging marker. The purpose of this study was to use high-gradient diffusion MRI and macromolecular tissue volume imaging to obtain estimates of axonal volume fraction, myelin volume fraction, and the imaging g-ratio in patients with MS and healthy controls and to explore their relationship to neurologic disability in MS. MATERIALS AND METHODS: Thirty individuals with MS (23 relapsing-remitting MS, 7 progressive MS) and 19 age-matched healthy controls were scanned on a 3T MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Macromolecular tissue volume imaging was performed to quantify the myelin volume fraction. Diffusion data were fitted to a 3-compartment model of white matter using a spheric mean approach to yield estimates of axonal volume fraction. The imaging g-ratio was calculated from the ratio of myelin volume fraction and axonal volume fraction. Imaging metrics were compared between groups using 2-sided t tests with a Bonferroni correction. RESULTS: The mean g-ratio was significantly elevated in lesions compared with normal-appearing WM (0.74 vs 0.67, P CONCLUSIONS: The imaging g-ratio may serve as a biomarker for the relative degree of axonal and myelin loss in MS.

Objective to develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods to illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results as of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD., The Guthy-Jackson Charitable Foundation, The CIRCLES Project

Background Gait disturbance is a major contributor to clinical disability in multiple sclerosis (MS). A sensor was developed to assess walking speed at home for people with MS using infrared technology in real-time without the use of wearables. Objective To develop continuous in-home outcome measures to assess gait in adults with MS. Methods Movement measurements were collected continuously for 8 months from six people with MS. Average walking speed and peak walking speed were calculated from movement data, then analyzed for variability over time, by room (location), and over the course of the day. In-home continuous gait outcomes and variability were correlated with standard in-clinic gait outcomes. Results Measured in-home average walking speed of participants ranged from 0.33 m/s to 0.96 m/s and peak walking speed ranged from 0.89 m/s to 1.51 m/s. Mean total within-participant coefficient of variation for daily average walking speed and peak walking speed were 10.75% and 10.93%, respectively. Average walking speed demonstrated a moderately strong correlation with baseline Timed 25-Foot Walk (rs = 0.714, P = 0.111). Conclusion New non-wearable technology provides reliable and continuous in-home assessment of walking speed.

An analysis of the annular induction MHD (magnetohydrodynamic) generator is carried out for a model employing a finite‐length winding and a constant‐velocity fluid flowing in the annulus. An expression for the phase impedance is derived which accounts for entrance and exit of the fluid into the winding region. Impedance characteristics are presented which allow comparison with the infinite‐length case in terms of dimensionless parameters.