Strategized Replication: Exploring Inconsistencies in QSM-Based Studies of Brain Iron in Multiple Sclerosis

Motivation: Contradicting evidence exists on thalamic iron alterations in multiple sclerosis, with most studies using susceptibility measurements reporting lower (susceptibility) iron but one study reporting higher. Goal(s): To investigate if the study reporting higher thalamic susceptibility can be reproduced. Approach: We matched demographics and clinical characteristics to the original study (higher susceptibility) and employed six QSM pipelines (two background field removal and three inversion algorithms). Results: Using the original study's pipeline, thalamic and putamen susceptibility was 8ppb (p=0.046) and 1ppb higher in patients, respectively. GP (-7 ppb) and caudate (-1 ppb) showed lower susceptibilities. Consistent group-differences with varying p-values were observed with each pipeline. Impact: This study was able to attribute inconsistencies in observed thalamic (susceptibility) iron alterations to the clinical and demographic characteristics of the studied cohort and provided support for the notion that study outcomes are comparable between different QSM pipelines.