Distinguishing microgliosis and tau deposition in the mouse brain using paramagnetic and diamagnetic susceptibility source separation

Motivation: Susceptibility source separation methods to disentangle sub-voxel paramagnetic and diamagnetic susceptibility sources may provide higher specificity to distinguish tissue microstructural alterations. Goal(s): Our goal was to investigate sub-cellular histopathological alterations in an established tauopathy mouse model using quantitative susceptibility source separation. Approach: Brains of PS19 mice and wild-type controls (n = 5 each) were imaged at 11.7 T. We used the DECOMPOSE-QSM model to calculate paramagnetic and diamagnetic component susceptibility maps. Results: Susceptibility maps revealed significant localized alterations in specific regions of the hippocampus and entorhinal cortex, which were found to correspond to regional microgliosis and tau deposition seen with immunohistology. Impact: Our findings demonstrate unique sensitivity of paramagnetic and diamagnetic susceptibility changes to distinguish regional microgliosis and tau deposition in the brain. Quantitative magnetic susceptibility source separation may therefore provide a sensitive method to assess sub-cellular histopathological alterations in tauopathies.