Perivascular Diffusivity and Periventricular Susceptibility Changes in Relapsing–Remitting Multiple Sclerosis: A Combined DTI ‐ ALPS and QSM Study

BACKGROUND: Progressive periventricular damage in multiple sclerosis (MS) has been linked to impaired perivascular clearance and to susceptibility changes attributed to iron deposition and myelin loss. Their relationship is unclear. PURPOSE/HYPOTHESIS: To compare diffusion tensor image analysis along the perivascular space (DTI-ALPS) and periventricular quantitative susceptibility mapping (QSM) between relapsing-remitting multiple sclerosis (RRMS) patients and healthy controls; and to evaluate their correlation and relationships with clinical disability (Expanded Disability Status Scale, EDSS). STUDY TYPE: Retrospective case-control study. POPULATION/SUBJECTS: Thirty one patients with RRMS (mean age, 34.6 ± 8.4 years) and 30 age- and sex-matched healthy controls (mean age, 34.2 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 1.5 T; Diffusion tensor imaging (DTI) and multi-echo gradient-echo (GRE) sequences. ASSESSMENT: DTI-ALPS index and periventricular QSM values were measured from manually placed bilateral regions of interest (ROIs). Standardized Montreal Neurological Institute (MNI)-space coordinates were used for DTI-ALPS analysis, and QSM ROIs in periventricular normal-appearing white matter were reviewed by a neuroradiologist. Disability was assessed using the EDSS. STATISTICAL TESTS: Groups were compared using independent-samples t-tests and Cohen's d. Correlations were assessed using Pearson's r, with Spearman's rho as a sensitivity analysis (p < 0.05, two-tailed). RESULTS: DTI-ALPS was lower in MS patients than controls (1.27 ± 0.22 vs. 1.45 ± 0.22; d = 0.828), whereas periventricular QSM was higher (-15.35 ± 4.92 vs. -21.70 ± 6.40 ppb; d = 1.116). A strong negative correlation between the two biomarkers was observed across all subjects (r = -0.738). Both measures correlated with EDSS (DTI-ALPS r = -0.509; QSM r = 0.501) and differed between EDSS subgroups (EDSS > 2.0 vs. ≤ 2.0: DTI-ALPS 1.160 vs. 1.364; QSM -12.33 vs. -17.83 ppb). DATA CONCLUSION: Reduced DTI-ALPS and higher periventricular QSM-derived susceptibility were each moderately associated with disability in RRMS. The negative DTI-ALPS-QSM correlation in both groups indicates an association between perivascular diffusivity, a putative marker of glymphatic function, and periventricular QSM-derived susceptibility; causality cannot be established from this cross-sectional design. STAGE OF TECHNICAL EFFICACY: 2.