Impaired glymphatic system function in relapsing-remitting multiple Sclerosis: Insights from diffusion tensor imaging along the perivascular space (DTI-ALPS)

Abstract

In relapsing-remitting multiple sclerosis (RRMS) patients, an enlarged perivascular space, cognitive impairment, and inflammatory immune response has been associated with the glymphatic dysfunction. Therefore, we employed the diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic function in RRMS patients. The study included 39 RRMS patients and 34 age- and gender-matched healthy controls (HC). We calculated the DTI-ALPS index by placing regions of interest (ROIs) in projection and association fiber areas, adjusting for any unsuitable positions following visual inspection. Lesion masks were created based on T2 FLAIR images, and then the measured diffusion coefficients along the x, y, and z axes were calculated after removing the lesion areas, and then DTI-ALPS index was calculated. The DTI-ALPS index between the RRMS and HC groups using two-sample t-test using SPSS 27.0. Additionally, we calculated DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Furthermore, we explored the association between the DTI-ALPS index and DTI metrics, as well as clinical variables such as disease duration and clinical disability score. The RRMS group showed a significantly lower DTI-ALPS index compared to HC group, suggesting altered water diffusivity along perivascular spaces. The DTI-ALPS index demonstrated a negative correlation with clinical disability and disease duration, with RRMS patients exhibiting decreased FA and increased MD, AD, and RD. These results suggest that changes in the DTI-ALPS index may be associated with microstructural damage and disease progression in RRMS, and may indirectly indicate impaired glymphatic function in RRMS.