Motivation: Ex-vivo histology is the most common method to assess iron accumulation in frontotemporal lobar degeneration, but in vivo assessment is crucial to unravel disease mechanisms. Goal(s): This study aims to assess the distribution and severity of iron accumulation post-mortem using susceptibility MRI and compare this to histological data. Approach: We analyzed postmortem tissue of 5 MAPT-FTLD and 2 C9orf72-FTLD cases using a histological iron staining, T2*-weighted MRI, and QSM maps. Results: We found that histology, susceptibility MRI, and QSM show good correspondence of iron distribution in FTLD brain tissue. However, sharp details are better seen on T2*-weighted MRI, and U-fibers on QSM maps. Impact: Our study showed that susceptibility-based imaging can be used to visualize iron accumulation in FTLD; with T2*-weighted MRI and QSM showing complementary spatial information. Therefore, these two methods should be used parallel and not independent of each other.

Analysis of Iron Accumulation in MAPT- and C9orf72-associated Frontotemporal Lobar Degeneration: QSM, T2*-w MRI, and Histology