Background: Meningeal inflammation may contribute to gray matter (GM) involvement in multiple sclerosis (MS) and is proposed to manifest as magnetic resonance imaging (MRI) leptomeningeal enhancement (LME). Objective: To investigate how LME relates to GM lesions in relapsing-remitting multiple sclerosis (RRMS) at 7T. Methods: A total of 30 RRMS subjects (age (mean ± standard deviation (SD)): 44.0 ± 11.3 years, 93% on disease-modifying treatment) and 15 controls underwent gadolinium-enhanced three-dimensional (3D) MP2RAGE (magnetization-prepared 2 rapid gradient-echo) and fluid-attenuated inversion recovery (FLAIR) MRI. LME, cortical lesions (CLs), thalamic lesions (TLs), and white matter (WM) lesions were expert-quantified. Wilcoxon rank-sum, two-sample t-tests, Spearman correlations, and regression models were employed. Results: Two-thirds (20/30) of MS subjects and 1/15 controls (6.7%) had LME. LME+ MS subjects had 2.7 ± 1.5 foci, longer disease duration (14.9 ± 10.4 vs. 8.1 ± 5.7 years, p = 0.028), increased CL number (21.5 ± 12.6 vs. 5.5 ± 5.0, p < 0.001) and volume (0.80 ± 1.13 vs. 0.13 ± 0.13 mL, p = 0.002), and increased TL number (3.95 ± 2.11 vs. 0.70 ± 1.34, p < 0.001) and volume (0.106 ± 0.09 vs. 0.007 ± 0.01 mL, p < 0.001) versus LME– subjects. LME focus number correlated more highly with CL ( rs = 0.50, p = 0.01) and TL ( rs = 0.81, p < 0.001) than WM lesion ( rs = 0.34, p > 0.05) volume. Similar LME–CL number associations were observed in unadjusted and WM lesion–adjusted comparisons (both p < 0.001). Conclusion: Cerebral LME is common in RRMS at 7T and is independently associated with GM injury. We hypothesize that cerebrospinal fluid (CSF)-related inflammation links cortical and thalamic injury.
IMPORTANCE MicroRNAs (miRNAs) are promising multiple sclerosis (MS) biomarkers. Establishing the association between miRNAs and magnetic resonance imaging (MRI) measures of disease severity will help define their significance and potential impact. OBJECTIVE To correlate circulating miRNAs in the serum of patients with MS to brain and spinal MRI. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study comparing serum miRNA samples with MRI metrics was conducted at a tertiary MS referral center. Two independent cohorts (41 and 79 patients) were retrospectively identified from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital. Expression of miRNA was determined by locked nucleic acid-based quantitative real-time polymerase chain reaction. Spearman correlation coefficients were used to test the association between miRNA and brain lesions (T2 hyperintense lesion volume [T2LV]), the ratio of T1 hypointense lesion volume [T1LV] to T2LV [T1:T2]), brain atrophy (whole brain and gray matter), and cervical spinal cord lesions (T2LV) and atrophy. The study was conducted from December 2013 to April 2016. MAIN OUTCOMES AND MEASURES miRNA expression. RESULTSOf the 120 patients included in the study, cohort 1 included 41 participants (7 [17.1%] men), with mean (SD) age of 47.7 (9.5) years; cohort 2 had 79 participants (26 [32.9%] men) with a mean (SD) age of 43.0 (7.5) years. Associations between miRNAs and MRIs were both protective and pathogenic. Regarding miRNA signatures, a topographic specificity differed for the brain vs the spinal cord, and the signature differed between T2LV and atrophy/destructive measures. Four miRNAs showed similar significant protective correlations with T1:T2 in both cohorts, with the highest for hsa.miR.143.3p
BACKGROUNDWhole brain atrophy is a putative outcome measure in monitoring relapsing‐remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC).METHODSWe studied MS [n = 26, age (mean, range) 43 (21‐55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0‐6.5), timed 25 foot walk (T25FW) 5.95 (3.2‐33.0 seconds)] and NC [n = 9, age 45 (31‐53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3‐dimensional T1‐weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations.RESULTSBPV‐1.5T was higher than BPV‐3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue‐CSF contrast at 3T. BPV‐3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [−74.5 mL (−126.5, −22.5), P = .006, d = .92] when compared to BPV‐1.5T [−51.3.1 mL (−99.8, −2.8), P = .04, d = .67]. Correlations between BPV‐1.5T and EDSS (r = −.43, P = .027) and BPV‐3T and EDSS (r = −.49, P = .011) and between BPV‐1.5T and T25FW (r = −.46, P = .018) and BPV‐3T and T25FW (r = −.56, P = .003) slightly favored 3T. BPV‐cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44‐.58) and 3T (r range = .43‐.53).CONCLUSIONSField strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.
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