Assessment of mesoscopic properties of deep gray matter iron through a model-based simultaneous analysis of magnetic susceptibility and R₂* - A pilot study in patients with multiple sclerosis and normal controls

Most studies of brain iron relied on the effect of the iron on magnetic resonance (MR) relaxation properties, such as R₂∗, and bulk tissue magnetic susceptibility, as measured by quantitative susceptibility mapping (QSM). The present study exploited the dependence of R₂∗ and magnetic susceptibility on physical interactions at different length-scales to retrieve information about the tissue microenvironment, rather than the iron concentration. We introduce a method for the simultaneous analysis of brain tissue magnetic susceptibility and R₂∗ that aims to isolate those biophysical mechanisms of R₂∗ -contrast that are associated with the micro- and mesoscopic distribution of iron, referred to as the Iron Microstructure Coefficient (IMC). The present study hypothesized that changes in the deep gray matter (DGM) magnetic microenvironment associated with aging and pathological mechanisms of multiple sclerosis (MS), such as changes of the distribution and chemical form of the iron, manifest in quantifiable contributions to the IMC. To validate this hypothesis, we analyzed the voxel-based association between R₂∗ and magnetic susceptibility in different DGM regions of 26 patients with multiple sclerosis and 33 age- and sex-matched normal controls. Values of the IMC varied significantly between anatomical regions, were reduced in the dentate and increased in the caudate of patients compared to controls, and decreased with normal aging, most strongly in caudate, globus pallidus and putamen.