Soma and neurite density abnormalities of paramagnetic rim lesions and core-sign lesions in multiple sclerosis

BACKGROUND: In multiple sclerosis (MS), susceptibility-weighted imaging (SWI) may reveal white matter lesions (WML) with a paramagnetic rim ("paramagnetic rim lesions" [PRLs]) or diffuse hypointensity ("core-sign lesions"), reflecting different stages of WML evolution. OBJECTIVE: Using the soma and neurite density imaging (SANDI) model on diffusion-weighted magnetic resonance imaging (MRI), we characterized microstructural abnormalities of MS PRLs and core-sign lesions and their clinical relevance. METHODS: Forty MS patients and 20 healthy controls (HC) underwent a 3 T brain MRI. Using SANDI, the fractions of neurite (fneurite) and soma (fsoma) and size of soma (rsoma) were quantified in PRLs (including their core and rim separately), and core-sign lesions identified on SWI-phase. RESULTS: Among 1811 WMLs, 122 (6.7%) core-sign lesions and 97 (5.4%) PRLs were identified. Compared to HC and MS normal-appearing white matter, all MS WML showed significantly lower fneurite and fsoma and higher rsoma (FDR-p < 0.001). Compared to SWI-isointense WML, core-sign lesions showed a significantly higher fneurite, and lower fsoma and rsoma (FDR-p ≤ 0.005). Compared to SWI-isointense WML and core-sign lesions, PRLs showed a significantly lower fneurite, higher fsoma, and higher rsoma (FDR-p ≤ 0.001). The PRL-core showed significantly lower fneurite, and higher rsoma than PRL-rim (FDR-p < 0.001). Lower PRL fneurite (β ≤ -0.006, FDR-p ≤ 0.015) and higher rsoma (β ≥ 0.032, FDR-p ≤ 0.024) were significantly associated with a longer disease duration and more severe disability. CONCLUSIONS: In PRLs, the significant and clinically relevant neurite loss and increased soma fraction and size possibly reflect increased astrogliosis and activated microglia. Core-sign lesions exhibit milder axonal loss, microglia density and astrogliosis, supporting their less destructive nature.