Ex vivo T2*-weighted MRI and quantitative susceptibility mapping reflect spatial iron accumulation observed on histology in frontotemporal lobar degeneration

Iron accumulation is known to be involved in frontotemporal lobar degeneration (FTLD) and possibly with a different spatial pattern in FTLD with tau (FTLD-tau) versus TDP-43 (FTLD-TDP) pathology. In this study, we aimed to visualize the spatial distribution of iron in ex vivo brain tissue with FTLD and healthy controls using both histology and MRI. High resolution multi-echo T2*-weighted 7 T MRI was performed on ex vivo tissue of the frontal and temporal cortex of 14 FTLD cases (6 FTLD-tau, 8 FTLD-TDP) and 11 healthy controls (HC) to obtain T2*-weighted images and quantitative susceptibility maps (QSM). These tissue blocks were then stained for iron. The spatial iron distribution was assessed visually by different scoring features on the three modalities (T2*-weighted MRI, QSM, and histology) and analyzing cortical layer profiles of the signal intensity. We found more iron accumulation in the temporal cortex of FTLD cases compared to HC, displayed by higher visual ratings and lower signal intensity values on cortical layer profiles. Histology showed a good correlation with T2*-weighted MRI. QSM offered complementary information compared to T2*-weighted MRI, particularly for identifying distinct histological features of iron accumulation within the subcortical U-fibers. We conclude that iron accumulation is involved in the disease process of FTLD and that T2*-weighted MRI and QSM can be used as a noninvasive imaging modality to study cortical and subcortical iron accumulation in FTLD.