Assessing Age-Associated Influences on Paramagnetic and Diamagnetic Susceptibility Maps in Postmortem Human Brains

Maps of paramagnetic and diamagnetic components of magnetic susceptibility can provide insights into the distribution of iron and myelin during brain aging. Postmortem validation is essential to ensure that these maps accurately reflect in vivo biological processes. In this study, we applied the APART-QSM method for susceptibility separation to in situ (intracranial) postmortem MRI data from 47 subjects (ages 31-91) to investigate how age affects magnetic susceptibility components, comparing the results with previously reported in vivo associations. Linear regression was used to assess age-related associations with susceptibility values in 17 deep gray matter (DGM) and white matter (WM) regions. Diamagnetic susceptibility showed a consistent age-related decline in DGM basal ganglia regions, which appeared to result from a shared underlying factor across these areas. Based on the assumption that fractional anisotropy (FA) reflects myelin integrity, we also investigated the correlation between FA and diamagnetic susceptibility in WM regions. A negative correlation was found, suggesting a potential myelin contribution to the diamagnetic component. Consistent with in vivo analyses, the putamen's paramagnetic and total QSM susceptibility values demonstrated a strong age association in our postmortem condition, and it was the only region in which susceptibility values increased linearly with age. Finally, the analysis of ex vivo putamen tissue samples revealed a moderate association between paramagnetic susceptibility and iron concentration, supporting iron's biological contribution to MRI paramagnetic susceptibility maps of the putamen. The results enhance the biological interpretability of MRI data and promote cross-validation between imaging and direct tissue analysis, with implications for both clinical and research applications related to aging and neurodegenerative diseases.