Atrophy-Independent and Dependent Iron and Myelin Changes in Deep Gray Matter of Multiple Sclerosis: A Longitudinal Study Using χ-Separation Imaging

Abstract

Rationale and objectives: To investigate iron and myelin changes in deep gray matter (DGM) of relapsing-remitting multiple sclerosis (RRMS) patients and their relationship to atrophy by χ-separation imaging.

Materials and methods: 33 RRMS patients and 34 healthy controls (HC) were included in this study. The χ-separation map reconstructed from a 3D multi-echo gradient echo scan was used to measure the positive susceptibility (χ_pos) and negative susceptibility (χ_neg) of DGM. To take into account the effect of atrophy, susceptibility mass of DGM was calculated by multiplying volume by the mean bulk susceptibility. Differences in MRI metrics between baseline patients, follow-up patients, and HC were compared respectively.

Results: Compared to HC, χ_pos of basal ganglia were significantly increased in follow-up patients (P < 0.05). The χ_pos of pallidum was significantly higher in follow-up patients than that in baseline patients (P = 0.006). The χ_neg of caudate, pallidum and hippocampus in baseline and follow-up patients was significantly higher than that in HC (P < 0.05). When taking into account the effect of atrophy, there was a significant decrease in χ_pos mass and a significant increase in χ_neg mass of thalamus, accumbens and amygdala in follow-up patients compared to HC (P < 0.05). The χ_pos mass of the thalamus was further decreased in follow-up patients compared to baseline patients (P = 0.006).

Conclusion: χ-separation imaging could generate independent information on iron and myelin changes in RRMS patients, showing atrophy-dependent iron increase in basal ganglia and atrophy-independent iron and myelin decrease in thalamus.

Keywords: Atrophy; Deep gray matter; Iron; Multiple sclerosis; Susceptibility source separation.