Microstructural alterations in different types of lesions and their perilesional white matter in relapsing-remitting multiple sclerosis based on diffusion kurtosis imaging

Background and Objectives: In multiple sclerosis (MS), contrast enhancement lesions and chronic active lesions have been demonstrated to have different degrees of inflammation. Accordingly, they exist different degrees of tissue damage, one is short and acute, and another is slow and longstanding. This study aimed to explore whether diffusion parameters can differentiate different types of lesions, and investigate the microstructural damage between different types of MS lesions by using diffusion magnetic resonance imaging (dMRI) and its correlation with clinical biomarkers of disability and cognitive states. Methods: We retrospectively identified 77 contrast enhancement lesions (CELs), 384 iron rim lesions (IRLs), 393 non-iron rim lesions (NIRLs), their corresponding perilesional white matter (PLWM), and 68 normal-appearing white matter (NAWM) from 68 relapsing-remitting MS (RRMS). Additionally, 44 white matter in healthy controls (WM in HCs) were also enrolled in this study. The DTI and DKI parameters were measured in the above white matter, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). All the patients were assessed with the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Expanded Disability Status Scale (EDSS). Results: The lowest KFA, FA, MK values and the highest MD values were found in CELs, followed by IRLs, NIRLs, NAWM, and WM in HCs. In KFA and FA values, there were significant differences between each type of lesion, as well as each type of PLWM (P < 0.05). The MK values of CELs and IRLs were significantly lower than NIRLs, but inversely for MD (P < 0.05). There were no differences between CELs and IRLs for MK (P = 1) and MD (P = 0.261). The results of MK and MD values in CELs-PLWM and IRLs-PLWM were similar to the CELs and IRLs. There were no significant differences between NAWM and WM in HCs in all the enrolled diffusion parameters (P >0.05) and the FA values between NIRLs-PLWM and NAWM or between NIRLs-PLWM and WM in HCs were no significant differences (P >0.05). The KFA and MD values in IRLs-PLWM (r =0.443, P =0.021; r =-0.518, P =0.006) were correlated with the DST scores and the KFA of CELs-PLWM (r =0.396, P =0.041) was correlated with SDMT scores. Conclusion: Our findings demonstrate that the KFA values have the potential to distinguish different types of MS white matter tissues. Furthermore, the diffusion parameters can reflect the microstructure abnormalities in different MS lesions and might help us better understand the pathological mechanism and lesion evolution.