Enlarged perivascular spaces are associated with more severe microstructural damage in white matter lesions among people with relapsing-remitting multiple sclerosis.

BACKGROUND AND OBJECTIVES: Growing evidence has linked MRI-visible perivascular spaces (PVS) to multiple sclerosis (MS) pathogenesis. However, whether PVS are associated with increased microstructural damage in white matter lesions (WML) remains unclear. Using diffusion kurtosis imaging (DKI), we aimed to explore the associations between PVS and the microstructural damage of WML in relapsing-remitting multiple sclerosis (RRMS) people with or without disease-modifying therapies (DMT) and their correlations with clinical biomarkers of disability and cognitive function. METHODS: The study included 68 people with RRMS and 47 age- and sex-matched HCs. WML were categorized into four groups based on two factors: whether the lesions were penetrated by perivascular spaces (P_WML vs. NP_WML) through visual assessment, and whether patients received DMT (MS + vs. MS-). The diffusion metrics, including fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), mean diffusivity (MD) and mean kurtosis (MK), were normalized using ROI-specific z-scores derived from HCs and used to assess the microstructural damage in WML. Lesion-wise group comparisons were performed using linear mixed-effects models and Spearman partial correlation analysis between diffusion metrics of WML and cognitive performance and clinical disability were performed. RESULTS: In the MS- and MS+ groups, the MKindex in P_WML was significantly lower than NP_WML (MS-: estimate [95%CI] = -1.23 [-2.24, -0.22], p = 0.009; MS+: estimate [95%CI] = -1.94 [-3.39, -0.49], p = 0.003). In the MS+ group, MKindex and MDindex in P_WML were significantly associated with the Montreal Cognitive Assessment scores in RRMS (MD: r [95%CI] = -0.71 [-0.90, -0.31], FDR-p = 0.016; MK: r [95%CI] = 0.69 [0.27, 0.90], FDR-p = 0.016). CONCLUSION: WML with PVS involvement exhibited distinct microstructural characteristics compared with WML without PVS involvement. Furthermore, diffusion abnormalities in WML may be related to cognitive performance in RRMS.