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.