Clinical relevance of paramagnetic rim lesion heterogeneity in multiple sclerosis.

Abstract

Objective: Previous studies reveal heterogeneity in terms of paramagnetic rim lesions (PRL) associated tissue damage. We investigated the physiopathology and clinical implications of this heterogeneity.

Methods: In 103 MS patients (72 relapsing and 31 progressive), brain lesions were manually segmented on 3T 3D-FLAIR and rim visibility was assessed with a visual confidence level score (VCLS) on 3D-EPI phase. Using T1 relaxation time maps, lesions were categorized in long-T1 and short-T1. Lesion age was calculated from time of first gadolinium enhancement (N = 84 lesions). Results on clinical scores were validated in an extended cohort of 167 patients using normalized T1w-MPRAGE lesion values.

Results: Rim visibility (VCLS analysis) was associated with increasing lesional T1 (P/P_FDR < 0.001). Of 1680 analyzed lesions, 427 were categorized as PRL. Long-T1 PRL were older than short-T1 PRL (average 0.8 vs. 2.0 years, P/P_FDR = 0.005/0.008), and featured larger lesional volume (P/P_FDR < 0.0001) and multi-shell diffusion-measured axonal damage (P/P_FDR < 0.0001). The total volume of long-T1-PRL versus PRL showed 2× predictive power for both higher MS disability (EDSS; P/P_FDR = 0.003/0.005 vs. P/P_FDR = 0.042/0.057) and severity (MSSS; P/P_FDR = 0.0006/0.001 vs. P/P_FDR = 0.004/0.007). In random forest, having ≥1 long-T1-PRL versus ≥4 PRL showed 2-4× higher performance to predict a higher EDSS and MSSS. In the validation cohort, long-T1 PRL outperformed (~2×) PRL in predicting both EDSS and MSSS.

Interpretation: PRL show substantial heterogeneity in terms of intralesional tissue damage. More destructive, likely older, long-T1 PRL improve the association with MS clinical scales. This PRL heterogeneity characterization was replicated using standard T1w MRI, highlighting its potential for clinical translation.