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 (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.
Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no competing interests in relation to this work. Potential conflicts of interest outside the submitted work are as follows: P. Preziosa received speaker honoraria from Roche, Biogen, Novartis, Merck, Bristol Myers Squibb, Genzyme, Horizon and Sanofi, he has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla; E. Pagani has nothing to disclose; A. Meani has nothing to disclose; M. Margoni reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almiral; M. Rubin has nothing to disclose; F. Esposito has nothing to disclose; M. Palombo has nothing to disclose; M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla; M.A. Rocca received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche, and speaker honoraria from AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva, she receives research support from the MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla, she is Associate Editor for Multiple Sclerosis and Related Disorders. Ethical approval: Approval was received from the institutional ethical standards committee on human experimentation of IRCCS Ospedale San Raffaele for any experiments using human subjects (Protocol N° 2015–33). Written informed consent was obtained from all subjects prior to study participation according to the Declaration of Helsinki.
(© 2025. Springer-Verlag GmbH Germany, part of Springer Nature.)