In-vivo Assessment of Cellular Soma and Neurite Density Abnormalities in Multiple Sclerosis Paramagnetic Rim and Core-sign Lesions
Paolo Preziosa1, Elisabetta Pagani3, Alessandro Meani3, Monica Margoni4, Martina Rubin1, Marco Palombo5, Massimo Filippi2, Maria Rocca1
1Neuroimaging Research Unit, Division of Neuroscience; and Neurology Unit, 2Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCCS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 3Neuroimaging Research Unit, Division of Neuroscience, 4Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit; and Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, 5Cardiff University Brain Research Imaging Centre, School of Psychology; and School of Computer Science and Informatics, Cardiff University
Objective:
Using soma and neurite density imaging (SANDI) method based on diffusion-weighted MRI, we characterized in vivo the microstructural abnormalities of multiple sclerosis (MS) white matter lesions (WML) showing a paramagnetic rim (paramagnetic rim lesions [PRL]) or diffuse hypointensity (“core-sign”) on susceptibility-weighted imaging (SWI) and their clinical relevance.
Background:
In MS, PRLs and core-sign lesions may underlie different stages of WML evolution, that are associated with a more severe disease course. By evaluating both soma and neurite properties, SANDI model may provide more speciļ¬c information about their heterogeneous pathological processes.
Design/Methods:
Forty MS patients and 20 healthy controls (HC) underwent a 3T 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.
Results:
Among 1811 WML, 122 (6.7%) core-sign lesions and 97 (5.4%) PRLs were identified. Compared to HC and MS NAWM, all MS WML showed significantly lower fneurite and fsoma and significantly higher rsoma (false discovery rate [FDR]-p<0.001). Compared to isointense WML, core-sign lesions showed a significantly higher fneurite (FDR-p<0.001), and lower fsoma and rsoma (FDR-p≤0.001). Compared to isointense WML and core-sign lesions, PRLs showed a significantly lower fneurite (FDR-p<0.001), and higher fsoma (FDR-p≤0.005) and rsoma (FDR-p<0.001). In the direct comparison, the PRL core showed significantly lower fneurite (FDR-p<0.001), and higher rsoma (FDR-p<0.001) than PRL rim. Lower fneurite (β≤-0.006, FDR-p≤0.015) and higher rsoma (β≥0.032, FDR-p≤0.024) of PRLs were significantly associated with a longer disease duration and higher Expanded Disability Status Scale score.
Conclusions:
PRLs are clinically-relevant lesions characterized by significant neurite loss and increase of soma fraction and size, potentially reflecting higher amount of activated microglia and astrogliosis. Core-sign lesions exhibit milder axonal loss and amount of microglia and astrogliosis, supporting their less destructive nature.