Evaluation of the Blood‐Brain Barrier, Demyelination, and Neurodegeneration in Paramagnetic Rim Lesions in Multiple Sclerosis on 7 Tesla MRI

Background Paramagnetic rim lesions (PRLs) are associated with chronic inflammation in multiple sclerosis (MS). 7‐Tesla (7T) magnetic resonance imaging (MRI) can evaluate the integrity of the blood‐brain barrier (BBB) in addition to the tissue myelination status and cell loss. Purpose To use MRI metrics to investigate underlying physiology and clinical importance of PRLs. Study Type Prospective. Subjects Thirty‐six participants (mean‐age 47, 23 females, 13 males) of mixed MS subtypes. Field Strength/Sequence 7T, MP2RAGE, MULTI‐ECHO 3D‐GRE, FLAIR. Assessment Lesion heterogeneity; longitudinal changes in lesion counts; comparison of T1, R2*, and χ ; association between baseline lesion types and disease progression (2–3 annual MRI visits with additional years of annual clinical follow‐up). Statistical Tests Two‐sample t ‐test, Wilcoxon Rank‐Sum test, Pearson's chi‐square test, two‐group comparison with linear‐mixed‐effect model, mixed‐effect ANOVA, logistic regression. P ‐values <0.05 were considered significant. Results A total of 58.3% of participants had at least one PRL at baseline. Higher male proportion in PRL+ group was found. Average change in PRL count was 0.20 (SD = 2.82) for PRLs and 0.00 (SD = 0.82) for mottled lesions. Mean and median pre‐/post‐contrast T1 were longer in PRL+ than in PRL−. No differences in mean χ were seen for lesions grouped by PRL ( P = 0.310, pre‐contrast; 0.086, post‐contrast) or PRL/M presence ( P = 0.234, pre‐contrast; 0.163, post‐contrast). Median χ were less negative in PRL+ and PRL/M+ than in PRL− and PRL/M−. Mean and median pre−/post‐contrast R2* were slower in PRL+ compared to PRL−. Mean and median pre−/post‐contrast R2* were slower in PRL/M+ than in PRL/M−. PRL presence at baseline was associated with confirmed EDSS Plus progression (OR 3.75 [1.22–7.59]) and PRL/M+ at baseline with confirmed EDSS Plus progression (OR 3.63 [1.14–7.43]). Data Conclusion Evidence of BBB breakdown in PRLs was not seen. Quantitative metrics confirmed prior results suggesting greater demyelination, cell loss, and possibly disruption of tissue anisotropy in PRLs. Evidence Level 2 Technical Efficacy Stage 2