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

Abstract

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 (f_neurite) and soma (f_soma) and size of soma (r_soma) 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 f_neurite and f_soma and higher r_soma (FDR-p < 0.001). Compared to SWI-isointense WML, core-sign lesions showed a significantly higher f_neurite, and lower f_soma and r_soma (FDR-p ≤ 0.005). Compared to SWI-isointense WML and core-sign lesions, PRLs showed a significantly lower f_neurite, higher f_soma, and higher r_soma (FDR-p ≤ 0.001). The PRL-core showed significantly lower f_neurite, and higher r_soma than PRL-rim (FDR-p < 0.001). Lower PRL f_neurite (β ≤ -0.006, FDR-p ≤ 0.015) and higher r_soma (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.

Keywords: Core-sign lesions; MRI; Multiple sclerosis; Paramagnetic rim lesions; SANDI; Susceptibility-weighted imaging.