T1-based stratification of paramagnetic rim lesions in multiple sclerosis: Evidence of microstructural heterogeneity and clinical implications

Background: Paramagnetic rim lesions (PRLs) in multiple sclerosis (MS) exhibited intrinsic heterogeneity. Objectives: We aimed to assess whether T1-intensity-based stratification captures PRL heterogeneity and its clinical associations. Methods: This prospective study included 112 patients with MS. PRLs were classified using corresponding T1-weighted black holes (BH) into four subtypes: PRL+BH+, PRL+BH−, PRL−BH+, PRL−BH−. The diffusion kurtosis metrics, neurite density index (NDI) and subvoxel paramagnetic/diamagnetic susceptibility were analyzed among different lesion types. Generalized linear mixed-effects models were used to assess associations between PRL subtype and clinical outcomes. Results: PRL+BH+ exhibited lower axial/radial/mean kurtosis, NDI and diamagnetic susceptibility (all p < 0.01) than PRL+BH−. PRL+BH+ volume correlated positively with higher EDSS (β = 0.061, 95% CI: 0.033 to 0.085, q < 0.001) and with lower SDMT (β = −2.096, 95% CI: −3.196 to −0.996, q = 0.009) and brain parenchymal volume (β = −2.928, 95% CI: −5.415 to −1.553 q < 0.001). Total PRL volume was associated with higher EDSS (β = 0.054, 95% CI: 0.033 to 0.075, q < 0.001). Conclusions: Our finding support the utility of T1-intensity for distinguishing heterogeneity within PRLs.