Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy?

BACKGROUND Magnetic resonance relaxometry studies in multiple sclerosis (MS) have suggested that iron accumulates within deep gray matter (DGM) structures early in the disease course. However, the commonly utilized mean R2* and magnetic susceptibility measures reflect regional iron concentration but not a structure's total iron content. Thus, tissue atrophy could impact mean R2* and magnetic susceptibility estimates. PURPOSE To demonstrate that both average iron concentration and total iron content need to be reported in order to distinguish between atrophy-related and definite magnetic susceptibility changes. STUDY TYPE Observational. POPULATION The study was performed on 30 healthy controls (HCs) and 39 people with definite MS. FIELD STRENGTH/SEQUENCE 3T Philips Achieva using an 8-channel SENSE head coil. R2* data were acquired using a multiecho gradient echo sequence and diffusion tensor imaging data were acquired using an echo-planar sequence. ASSESSMENT Total iron content in DGM structures was assessed by calculating the sum of all R2* values within a region (denoted as R2mass* ) and compared to the mean R2* as a measure of iron concentration. STATISTICAL TEST Significant group differences were investigated in a linear regression model. All DGM structures were assessed individually and the significance threshold was adjusted using the Bonferroni-Holm correction for multiple comparisons. RESULTS There was an increased mean DGM R2* in MS patients compared to HCs (significant in the pallidus, P = 0.0051). In contrast, R2mass* in patients was found to be lower in the thalamus and the caudate (P = 0.0011) compared to HCs, and similar between the two cohorts in the other DGM regions. DATA CONCLUSION An increase in mean R2* may not necessarily reflect increased iron accumulation. We propose R2mass* as an additional metric to account for the effects of tissue atrophy when assessing tissue content changes, such as iron deposition or loss. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:201-208.