PURPOSE:To develop a generative diffusion model-based approach for robust and efficient quantitative susceptibility mapping (QSM) reconstruction in intracranial hemorrhage (ICH), applicable to both standard gradient echo (GRE) and rapid echo planar imaging (EPI) acquisitions. METHODS:QSMDiff, an unsupervised diffusion model for 3D QSM dipole inversion, was proposed. Three volumetric partitioning strategies including 2D slices, 3D patches, and 2.5D slabs were evaluated, and the memory-efficient 2.5D slab approach was adopted to balance accuracy and efficiency while maintaining anatomical fidelity. A conditional sampling mechanism ensured consistency with measured local fields, and a three-stage training data-generation strategy combining public dataset, synthetic QSM, and ICH lesions simulated from in vivo patients was implemented to overcome data scarcity. RESULTS:QSMDiff achieved the best overall performance in simulation studies, with SSIM of 0.97 ± 0.07, RMSE of 0.04 ± 0.03, and HFEN of 4.49 ± 0.83, demonstrating superior structural fidelity and noise suppression. For in vivo ICH patients scanned with rapid EPI, QSMDiff showed strong agreement with SWI-QSM references (R2 = 0.83), producing susceptibility estimates with minimal bias and variance. Qualitative evaluation confirmed enhanced resolution and effective artifact suppression in conditions of low SNR, limited resolution, and motion. CONCLUSION:QSMDiff achieves high-quality and accurate QSM reconstruction from both standard GRE and rapid EPI scans for ICH assessment. By integrating a 2.5D training strategy with synthetic ICH augmentation, it delivers accurate and reliable susceptibility maps even from lower-quality acquisitions, offering a practical solution for fast and robust ICH assessment.

Diffusion tensor imaging (DTI) can infer microstructural changes in white matter tracts like the fornix (main efferent tract of the hippocampus), where there is limited knowledge on typical changes with age from childhood through adulthood, and on whether DTI deviations in multiple sclerosis (MS) are consistent across the lifespan. The objectives are to determine fornix DTI age relationships in healthy controls and characterize DTI deviations in MS. High-resolution, fluid-suppressed DTI tractography quantified fornix volume and DTI parameters (fractional anisotropy - FA; mean, axial, radial diffusivity - MD, AD, RD) in 103 healthy controls (12-65 years) and 42 MS participants (13-63 years). Other brain volumes were measured on T1-weighted MPRAGE. All parameters were assessed for age trajectories, compared between groups, and correlated to clinical/cognitive assessments in MS. Control fornix volume increased markedly (~1.7x) from 12 to 33 years and then declined to a similar extent by 65 years, while MD, AD, and RD showed U-shaped changes with minima ~30-33 years; conversely, FA showed no age relationship. MS fornix volume followed a similar age trend, but remained below controls at all ages and was proportionally reduced (-29%) more than all other brain volumes. In contrast, age relationships of MD, AD, and RD were lost due to similarly higher diffusivity in MS over all ages and FA was below controls across all ages. MS fornix volume/diffusion metrics correlated with various clinical/cognitive scores. Fluid-suppressed, high-resolution diffusion tractography showed nonlinear changes of the fornix in controls over the observed lifespan and early deviations in MS, consistent across age, suggesting it is an early target of injury.

PURPOSE:Monte Carlo simulations and short diffusion time measurements have suggested neurite beading and swelling as the underlying mechanism of reduced diffusion in acute stroke, although the observed diffusion time dependence is often heterogeneous and not yet fully understood. This study aimed to investigate the heterogeneity of diffusion time effects in ischemic lesions and explore the potential microstructural basis with Monte Carlo simulations. METHODS:Pulsed gradient spin echo (PGSE, diffusion time 40 ms) and oscillating gradient spin echo (OGSE 40 Hz, diffusion time ˜5.1 ms) were acquired within 5 min in 39 acute ischemic stroke patients at 3 T. Mean, axial, and radial diffusivity differences between OGSE and PGSE (ΔMD/ΔAD/ΔRD) were compared between lesion and contralateral tissues (white and gray matter). Monte Carlo diffusion simulations of beaded axons for the experimental waveforms were used to investigate the effects of neurite morphology on time-dependent diffusivity changes. RESULTS:PGSE yielded the typical mean diffusivity (MD) reduction of -40 ± 10% in ischemic lesions, whereas it was less at -29 ± 11% for OGSE 40 Hz. The OGSE-PGSE diffusion time difference was greater in lesions (ΔMD = 0.12 ± 0.06 × 10-3 mm2/s) than contralateral white matter (ΔMD = 0.04 ± 0.06 × 10-3 mm2/s), consistent with larger beading amplitude (0.18-0.43) and intracellular volume fraction (0.61-0.78) in lesions. ΔMD maps revealed regional variation with the largest effects in internal capsule and corona radiata. CONCLUSION:This study found greater diffusion time effects in ischemic regions with purportedly larger axons. Monte Carlo simulations further support that the pronounced OGSE-PGSE diffusivity differences are expected in large axons with high beading amplitude.

T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) is commonly included in brain studies for structural imaging using magnitude images; however, its phase images can provide an opportunity to assess microbleed burden using quantitative susceptibility mapping (QSM). This potential application for MPRAGE-based QSM was evaluated using in vivo and simulated measurements. Possible factors affecting image quality were also explored. Detection sensitivity was evaluated against standard multiecho gradient echo (MEGE) QSM using 3-T in vivo data of 15 subjects with a combined total of 108 confirmed microbleeds. The two methods were compared based on the microbleed size and susceptibility measurements. In addition, simulations explored the detection sensitivity of MPRAGE-QSM at different representative magnetic field strengths and echo times using microbleeds of different size, susceptibility, and location. Results showed that in vivo microbleeds appeared to be smaller (× 0.54) and of higher mean susceptibility (× 1.9) on MPRAGE-QSM than on MEGE-QSM, but total susceptibility estimates were in closer agreement (slope: 0.97, r 2 : 0.94), and detection sensitivity was comparable. In simulations, QSM at 1.5 T had a low contrast-to-noise ratio that obscured the detection of many microbleeds. Signal-to-noise ratio (SNR) levels at 3 T and above resulted in better contrast and increased detection. The detection rates for microbleeds of minimum one-voxel diameter and 0.4-ppm susceptibility were 0.55, 0.80, and 0.88 at SNR levels of 1.5, 3, and 7 T, respectively. Size and total susceptibility estimates were more consistent than mean susceptibility estimates, which showed size-dependent underestimation. MPRAGE-QSM provides an opportunity to detect and quantify the size and susceptibility of microbleeds of at least one-voxel diameter at B 0  of 3 T or higher with no additional time cost, when standard T 2 *-weighted images are not available or have inadequate spatial resolution. The total susceptibility measure is more robust against sequence variations and might allow combining data from different protocols.

Introduction: Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15-20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear. Methods: A multicenter, observational study of 215 vaccine-na & iuml;ve patients with clinically recovered COVID-19, studied at 3-6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized. Discussion: Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease.

Background Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. Purpose To apply susceptibility separation ( χ separation) to follow lesion evolution in MS with comparison to R 2 */R 2 ′ /QSM. Study Type Longitudinal, prospective. Subjects Twenty relapsing–remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years). Field Strength/Sequence Three‐dimensional multiple echo gradient echo (QSM and R 2 * mapping), two‐dimensional dual echo fast spin echo (R 2 mapping), T 2 ‐weighted fluid attenuated inversion recovery, and T1‐weighted magnetization prepared gradient echo sequences at 3 T. Assessment Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid‐attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R 2 * or separated into positive/negative components from χ separation. Statistical Tests Two‐sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R 2 */R 2 ′ /QSM. Significant level: P < 0.005. Results A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R 2 */R 2 ′ . When lesions were grouped based on changes in QSM and R 2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility‐sensitive MRI indices and χ separation. Data Conclusion Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R 2 * and QSM alone. Level of Evidence 2 Technical Efficacy Stage 2

To report the accuracy and reliability of Cobb angle (CA), axial vertebral rotation (AVR), kyphotic and lordotic angles (KA and LA) measurements on using a new 3D ultrasound (US) system. Forty participants (34 F, 6 M, aged 14.0 ± 2.3 years) were recruited. The first 20 participants were scanned by the validated US system and the new US system. The other 20 participants were scanned with the new US system only. Two raters (R1 and R2) performed the measurements: R1 has 10 years of experience in radiology but is new in ultrasound scoliosis, while R2 has 30 years of scoliosis experience. All US images were measured twice by R1, and once by R2. Forty posteroanterior and 30 lateral standing radiographs were obtained and measured once by R1. Statistical analysis consisted of mean absolute difference (MAD), intraclass correlation coefficient (ICC (2,1)), and Bland-Altman plots. R1 showed excellent intra-rater and inter-rater reliability for US measurements with ICCs(2,1) ≥ 0.91. The inter-method reliability was good between the two US systems for all parameters with ICCs(2,1) ≥ 0.85 and maximum MAD of 3.4°. The new US showed good reliability and accuracy compared to radiographs for CA, AVR and KA with ICCs(2,1) ≥ 0.81 and maximum MAD of 5.8°, but poor results for LA with ICCs(2,1) of 0.27–0.35 and MADs of 14.0°-15.4°. The new 3D US system showed good reliability and accuracy for CA, AVR and KA measurements, but a large measurement discrepancy on LA. A new measurement method for US LA may need to investigate.

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Hippocampus demyelinating lesions in multiple sclerosis (MS) have been frequently observed in ex vivo histopathological studies; however, they are difficult to image and quantify in vivo. Diffusion tensor imaging (DTI) and T2 mapping could potentially detect such regional in vivo changes if acquired with sufficient spatial resolution. The goal here was to evaluate whether there are focal hippocampal abnormalities in 43 MS patients (35 relapsing-remitting, eight secondary progressive) with and without cognitive impairment (CI) versus 43 controls using high-resolution 1 mm isotropic DTI, as well as complementary methods of T2-weighted and T2 mapping at 3 T. Abnormal hippocampus regions were identified voxel-by-voxel by using mean diffusivity (MD)/T2 thresholds and avoiding voxels attributed to cerebrospinal fluid. When compared with controls, averaged left/right whole hippocampus MD was higher in both MS groups, while lower fractional anisotropy (FA) and volume, and higher T2 relaxometry and T2-weighted signal values, were only significant in CI MS. The hippocampal MD and T2 images/maps were not uniformly affected and focal regions of elevated MD/T2 were evident in MS patients. Both CI and not CI MS groups showed greater proportional areas of the hippocampus with elevated MD, whereas only the CI group showed a greater proportional area of elevated T2 relaxation times or T2-weighted signal. Higher T2 relaxometry and T2-weighted signal values of elevated regions correlated with greater disability and whole hippocampus FA negatively correlated with physical fatigue. High-resolution hippocampus DTI and T2 mapping with less partial volume effects showed whole hippocampus abnormalities with regional elevations of MD/T2 in MS, which could be interpreted as potentially from demyelination, neuron loss, and/or inflammation, and which overall were more extensive in the hippocampus of patients with larger total brain lesion volumes and CI.

PURPOSE:Tensor-valued diffusion encoding can disentangle orientation dispersion and subvoxel anisotropy, potentially offering insight into microstructural changes after cerebral ischemia. The purpose was to evaluate tensor-valued diffusion MRI in human acute ischemic stroke, assess potential confounders from diffusion time dependencies, and compare to Monte Carlo diffusion simulations of axon beading. METHODS:Linear (LTE) and spherical (STE) b-tensor encoding with inherently different effective diffusion times were acquired in 21 acute ischemic stroke patients between 3 and 57 h post-onset at 3 T in 2.5 min. In an additional 10 patients, STE with 2 LTE yielding different effective diffusion times were acquired for comparison. Diffusional variance decomposition (DIVIDE) was used to estimate microscopic anisotropy (μFA), as well as anisotropic, isotropic, and total diffusional variance (MKA , MKI , MKT ). DIVIDE parameters, and diffusion tensor imaging (DTI)-derived mean diffusivity and fractional anisotropy (FA) were compared in lesion versus contralateral white matter. Monte Carlo diffusion simulations of various cylindrical geometries for all b-tensor protocols were used to interpret parameter measurements. RESULTS:MD was ˜40% lower in lesions for all LTE/STE protocols. The DIVIDE parameters varied with effective diffusion time: higher μFA and MKA in lesion versus contralateral white matter for STE with longer effective diffusion time LTE, whereas the shorter effective diffusion time LTE protocol yielded lower μFA and MKA in lesions. Both protocols, regardless of diffusion time, were consistent with simulations of greater beading amplitude and intracellular volume fraction. CONCLUSION:DIVIDE parameters depend on diffusion time in acute stroke but consistently indicate neurite beading and larger intracellular volume fraction.

Short diffusion time oscillating gradient spin echo (OGSE) showed less water diffusion reduction in acute human stroke lesions (n=28) than the typical clinically used long diffusion time pulsed gradient spin echo (PGSE) method. The diffusion time dependency is far greater in ischemic lesions, particularly white matter, than in contralateral healthy brain. These effects were heterogeneous across the lesion with larger OGSE-PGSE differences in regions indicative of larger axons. The range of MD decrease in lesions across patients as measured with OGSE and PGSE showed a linear correlation and is consistent with concomitant axon beading and swelling implied from prior simulations.

Skin moles are one of the most critical conditions for early diagnosis of severe conditions such as melanoma. Early identification of moles has become crucial nowadays, primarily due to malignant melanoma, a dangerous type of skin cancer. Most of the recent advances concerning this domain of dermatology deal mostly with either classifying moles as benign or malignant or with methods that help delineate moles from skin images. However, there are minimal sources of exploration in just determining whether moles are present in a given query image. In this paper, we have employed the latest state-of-the-art neural networks to identify the presence of moles in dermatological images uploaded by patients on an online teledermatology platform. This filter flags if a mole is detected, which can be employed as a triage system that helps the dermatologist diagnose and ease the follow-up treatment procedure in a physical setting if the patient has a mole in their image. A comparative study of the prediction performance of the different models has been provided for different performance metrics of interest. The results presented in this paper have been obtained from two sets of data, consisting of more than 26,000 clinical pictures with different conditions combined. Multiple experiments using different models yielded a macro average recall value as high as 0.955, along with overall accuracy and macro average precision values of 0.962 and 0.958, respectively.

Purpose: To optimize quantitative susceptibility-weighted imaging also known as true susceptibility-weighted imaging (tSWI) for strong susceptibility sources like hemorrhage and compare to standard susceptibilityweighted imaging (SWI) and quantitative susceptibility mapping (QSM). Methods: Ten patients with known intracerebral hemorrhage (ICH) were scanned using a 3D SWI sequence. The magnitude and phase images were utilized to compute QSM, tSWI and SWI images. tSWI parameters including the upper threshold for creating susceptibility-weighted masks and the multiplication factor were optimized for hemorrhage depiction. Combined tSWI was also computed with independent optimized parameters for both veins and hemorrhagic regions. tSWI results were compared to SWI and QSM utilizing region-of-interest measurements, Pearson's correlation and Kruskal-Wallis test. Results: Fifteen hemorrhages were found, with mean susceptibility 0.81 +/- 0.37 ppm. Unlike SWI which utilizes a phase mask, tSWI uses a mask computed from QSM. In tSWI, the weighted mask required an extended upper threshold far beyond the standard level for more effective visualization of hemorrhage texture. The upper threshold was set to the mean maximum susceptibility in the hemorrhagic region (3.24 ppm) with a multiplication factor of 2. The blooming effect, seen in SWI, was observed to be larger in hemorrhages with higher susceptibility values (r = 0.78, p < 0.001) with reduced blooming on tSWI. On SWI, 4 out of 15 hemorrhages showed phase wrap artifacts in the hemorrhagic region and all patients showed some phase wraps in the airtissue interface near the auditory and frontal sinuses. These phase wrap artifacts were absent on tSWI. In hemorrhagic regions, a higher correlation was observed between the actual susceptibility values and mean gray value for tSWI (r = -0.93, p < 0.001) than SWI (r = -0.87, p < 0.001). Conclusion: In hemorrhage, tSWI minimizes both blooming effects and phase wrap artifacts observed in SWI. However, unlike SWI, tSWI requires an altered upper threshold for best hemorrhage depiction that greatly differs from the standard value. tSWI can be used as a complementary technique for visualizing hemorrhage along with SWI.

ABSTRACT:Brain magnetic resonance imaging (MRI) studies of clinical populations often require comparison to a normative ‘control’ cohort, usually of similar age/sex, scanned with the same protocol. The goal here was to create a normative brain MRI database of common quantitative methods to be used in comparisons with a variety of neurological disorders across the lifespan. 378 neurotypical controls (aged 5–90 years; median 31 years; 216 females, 162 males) completed brain MRI, cognitive testing, clinical assessment, and a demographics questionnaire. In addition, this large normative sample will yield novel insight into healthy brain development and aging.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

A 36-year-old man with a 9-year history of stable, relapsing-remitting multiple sclerosis (MS) presented to the emergency department with a 1-week history of blurred vision, vertigo, perioral numbness, difficulty walking, aggression and confusion. Symptoms persisted despite the patient having

[Voir la version anglaise de l’article ici: www.cmaj.ca/lookup/doi/10.1503/cmaj.211807][1] Un homme de 36 ans atteint depuis 9 ans d’une sclérose en plaques (SP) cyclique stable a consulté au service des urgences pour vision trouble, vertiges, engourdissement périoral, difficulté à la

Multi-site imaging consortiums strive to increase participant numbers by pooling data across sites, but scanner related differences can bias results. This study combines data from three research MRI centers, including three different scanner models from two vendors, to examine non-harmonized T1-weighted brain imaging protocols in two cohorts. First, 23 human traveling phantoms were scanned twice each at all three sites (six scans per person; 138 scans total) to quantify within-participant variability of brain volumes (total brain, white matter, gray matter, lateral ventricles, thalamus, caudate, putamen and globus pallidus), and to calculate site-specific correction factors for each structure. Sample size calculations were used to determine the number of traveling phantoms needed to achieve effect sizes for observed differences to help guide future studies. Next, cross-sectional lifespan volume trajectories were examined in 856 healthy participants (5-91 years of age) scanned at these sites. Cross-sectional trajectories of volume versus age for each structure were then compared before and after application of traveling phantom based site-specific correction factors, as well as correction using the open-source method ComBat. Although small systematic differences between sites were observed in the traveling phantom analysis, correction for site using either method had little impact on the lifespan trajectories. Only white matter had small but significant differences in the intercept parameter after ComBat correction (but not traveling phantom based correction), while no other fits differed. This suggests that age-related changes over the lifespan outweigh systematic differences between scanners for volumetric analysis. This work will help guide pooling of multisite datasets as well as meta-analyses of data from non-harmonized protocols.

Introduction: The source of Tissue Sodium Concentration (TSC) increase in Multiple Sclerosis (MS) remains unclear, and could be attributed to altered intracellular sodium concentration or tissue microstructure. This paper investigates sodium in MS using three new MRI sequences.Methods: Three sodium scans were acquired at 4.7 T from 30 patients (11 relapsing-remitting, 10 secondary-progressive, 9 primary-progressive) and 9 healthy controls including: Density-Weighted (NaDW), with very short 30° excitation for more accurate TSC measurement; Projection Acquisition with Coherent MAgNetization (NaPACMAN), designed for enhanced relaxation-based contrast; and Soft Inversion Recovery FLuid Attenuation (NaSIRFLA), developed to reduce fluid space contribution. Signal was measured in both lesions (n = 397) and normal appearing white matter (NAWM) relative to controls in the splenium of corpus callosum and the anterior and posterior limbs of internal capsule. Correlations with clinical and cognitive evaluations were tested over all MS patients.Results: Sodium intensity in MS lesions was elevated over control WM by a greater amount for NaPACMAN (75%) than NaDW (35%), the latter representing TSC. In contrast, NaSIRFLA exhibited lower intensity, but only for region specific analysis in the SCC (−7%). Sodium intensity in average MS NAWM was not significantly different than control WM for either of the three scans. NaSIRFLA in the average NAWM and specifically the posterior limb of internal capsules positively correlated with the Paced Auditory Serial Addition Test (PASAT).Discussion: Lower NaSIRFLA signal in lesions and ~2× greater NaPACMAN signal elevation over control WM than NaDW can be explained with a demyelination model that also includes edema. A NAWM demyelination model that includes tissue atrophy suggests no signal change for NaSIRFLA, and only slightly greater NAWM signal than control WM for both NaDW and NaPACMAN, reflecting experimental results. Models were derived from previous total and myelin water fraction study in MS with T2-relaxometry, and for the first time include sodium within the myelin water space. Reduced auditory processing association with lower signal on NaSIRFLA cannot be explained by greater demyelination and its modeled impact on the three sodium MRI sequences. Alternative explanations include intra- or extracellular sodium concentration change. Relaxation-weighted sodium MRI in combination with sodium-density MRI may help elucidate microstructural and metabolic changes in MS.