Monitoring Remyelination and Its Association With Disability Improvement in Multiple Sclerosis Using APART‐QSM: A Longitudinal Cohort Study

ABSTRACT Background Conventional MRI has limited specificity for myelin quantification. IterAtive magnetic suscePtibility sources sepARaTion quantitative susceptibility mapping (APART–QSM) quantifies myelin–sensitive (χ dia ) and iron–sensitive (χ para ) susceptibility components, but its value for longitudinal assessment of remyelination in multiple sclerosis (MS) remains unclear. Purpose To characterize longitudinal χ dia in MS and assess its associations with clinical characteristics. Study Type Prospective, longitudinal. Population One hundred forty–five patients with MS and 65 healthy controls (HCs). Field Strength/Sequence 3.0T; 3D T1 –weighted, 3D FLAIR , 3D DIR , and multi‐echo gradient‐echo imaging sequences. Assessment APART‐QSM generated χ dia and χ para maps, with susceptibility quantified in lesions and non–lesional regions, and the Expanded Disability Status Scale (EDSS) assessed at baseline and follow–up. Statistical Tests Chi–square, Mann–Whitney U, Wilcoxon signed–rank, Friedman tests, linear mixed‐effects models, linear and nonlinear regression. A p value < 0.05 was considered significant. Results One hundred one patients with MS and 20 HCs completed follow–up after a median (IQR) interval of 1.0 (0.8) and 1.25 (0.2) years, respectively. At baseline, white matter lesions (WMLs) exhibited lower χ dia (0.0131 [IQR 0.0087] ppm) and higher χ para (0.0058 [IQR 0.0049] ppm) than corresponding normal‐appearing white matter (NAWM) (0.0191 [0.0088] ppm; 0.0036 [0.0038] ppm; both p < 0.001). Over 1 year, χ dia in WMLs increased (0.0122 [IQR 0.0069] vs. 0.0152 [IQR 0.0065] ppm, p < 0.001), particularly in ofatumumab‐treated patients (0.0114 [IQR 0.0085] vs. 0.0158 [IQR 0.0081] ppm, p < 0.001). Greater increases in χ dia were significantly associated with female sex, ofatumumab treatment, relapsing–remitting phenotype, and EDSS improvement (all Bonferroni correction p < 0.01). Δχ dia showed a nonlinear decline with increasing disease duration (effective degrees of freedom ( edf ) = 1.83, p = 0.002). Conclusion APART–QSM may enable longitudinal monitoring of remyelination–related changes in MS, with declining Δχ dia over disease duration potentially informing individualized treatment strategies. Level of Evidence 2. Stage of Technical Efficacy 2.