Longitudinal diffusion tensor magnetic resonance imaging analysis at the cohort level reveals disturbed cortical and callosal microstructure with spared corticospinal tract in the TDP-43G298S ALS mouse model

Background In vivo diffusion tensor imaging (DTI) of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis (ALS). Methods Ten mice with TDP-43(G298S) overexpression under control of the Thy1.2 promoter and 10 wild type (wt) underwent longitudinal DTI scans at 11.7 T, including one baseline and one follow-up scan with an interval of about 5 months. Whole brain-based spatial statistics (WBSS) of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43(G298S) mice compared to wt at the cohort level. Results were supplemented by tractwise fractional anisotropy statistics (TFAS) and histological evaluation of motor cortex for signs of neuronal loss. Results Alterations at the cohort level in TDP-43(G298S) mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal tract. Neuronal loss in layer V of motor cortex was detected in TDP-43(G298S) at the later (but not at the earlier) timepoint compared to wt. Conclusion DTI mapping of TDP-43(G298S) mice demonstrated progression in motor areas M1/M2. WBSS and TFAS are useful techniques to localize TDP-43(G298S) associated alterations over time in this ALS mouse model, as a biological marker.