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

Abstract

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.

Keywords: disease progression; multiple sclerosis; paramagnetic rim lesion; ultra-high field MRI.

Figure 1:

Paramagnetic rim lesion (PRL, yellow arrow) seen on the various contrasts used in this study. (a) T1-w from MP2RAGE, (b) T1 map from MP2RAGE, (c) Quantitative susceptibility map (QSM), (d) R2* map, (e) ΔT1 map (color scale in seconds).

Figure 2:

Examples of paramagnetic rim lesion (PRL+) (a, d), mottled (M+) (b, e), non-PRL/M lesions (c, f) on QSM.

Figure 3:

Mean and median values of T1 measures, R2* measures, and magnetic susceptibility (χ) measures for PRL + vs. PRL −: Both PRL+ and PRL− lesions show significant reduction in mean and median post-contrast T1 values (a, d). PRL−, not PRL+, lesions show significant increase in mean and median post-contrast R2* values (b, e). Neither PRL+ nor PRL− show significant changes in χ (c, f). Significance noted using “*** 0.001, ** 0.01, *0.05”

Figure 4:

Mean and median values of T1 measures, R2* measures, and magnetic susceptibility (χ) measures for PRL/M+ vs. PRL/M−: Both PRL/M+ and PRL/M− lesions show significant reduction in mean and median post-contrast T1values (a, d). PRL/M−, not PRL/M+, lesions show significant increase in mean and median post-contrast R2* values (b, e). Neither PRL/M+ nor PRL/M− show significant changes in χ (c, f). Significance noted using “*** 0.001, ** 0.01, *0.05”