On the Impact of QSM Pipeline Parameters on Brain Iron Outcomes

Motivation: Only two quantitative susceptibility mapping (QSM) studies so far observed increased susceptibility in the thalamus of people with multiple sclerosis (pwMS), while all others found lower. Goal(s): Investigate whether discrepancies in reported thalamic iron levels in pwMS can be attributed to age differences in studies or variations in their QSM processing pipeline. Approach: We replicated a previous study's QSM pipeline with matched cohorts and systematically varying the regularization parameters for background field removal and dipole inversion. Results: We found that pwMS consistently exhibited lower thalamic susceptibility across all pipeline parameter settings. Impact: Our findings suggest that neither younger age nor specific regularization parameter choices account for the discrepancies in the literature, and that QSM robustly detects disease-related effects independent of these parameter variations.