Decoding Deep Gray Matter Susceptibility: Variance from the reference region, not dipole inversion artifacts, dominates reproducibility

Motivation: Quantitative Susceptibility Mapping (QSM), an MRI technique used to investigate iron, myelin and calcium in neurology research, necessitates referencing susceptibility values, but the effect of this referencing step on the study outcome is not well understood. Goal(s): To disentangle the impact of reference region and inversion algorithm on scan-rescan susceptibility variation. Approach: Three brain reference regions and twenty-one inversion algorithms were studied on DGM susceptibility reproducibility using 5 subjects (4 scan-rescan each). Results: The choice of the reference region had a more significant impact on reproducibility than the choice of the inversion algorithms. Whole brain and white matter referenced findings were highly reproducible. Impact: The choice of the reference region affects statistical power and can lead to the masking of significant group differences due to increased variation.