Biophysical contrast sources for magnetic susceptibility and R2* mapping: A combined 7 Tesla, mass spectrometry and electron paramagnetic resonance study

Iron is the most abundant trace metal in the human brain and consistently shown elevated in prevalent neurological disorders. Because of its paramagnetism, brain iron can be assessed in vivo by quantitative MRI techniques such as R₂* mapping and Quantitative Susceptibility Mapping (QSM). While Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has demonstrated good correlations of the total iron content to MRI parameters in gray matter, the relationship to ferritin levels as assessed by Electron Paramagnetic Resonance (EPR) has not been systematically analyzed. Therefore, we included 15 postmortem subjects (age: 26-91 years) which underwent quantitative in-situ MRI at 7 Tesla within a post-mortem interval of 24 h after death. ICP-MS and EPR were used to measure the total iron and ferritin content in 8 selected gray matter (GM) structures and the correlations to R₂* and QSM were calculated. We found that R₂* and QSM in the iron rich basal ganglia and the red nucleus were highly correlated with iron (R² > 0.7) and ferritin (R² > 0.6), whereas those correlations were lost in cortical regions and the hippocampus. The neuromelanin-rich substantia nigra showed a different behavior with a correlation with total iron only (R² > 0.5) but not with ferritin. Although qualitative results were similar for both qMRI techniques the observed correlation was always stronger for QSM than R₂*. This study demonstrated the quantitative correlations between R₂*, QSM, total iron and ferritin levels in an in-situ MRI setup and therefore aids to understand how molecular forms of iron are responsible for MRI contrast generation.