Longitudinal T2 MRI and spectroscopy are sensitive to neuronal damage in an inducible TDP-43 mouse model of ALS

Motivation: MRI is commonly used to monitor different neuropathologies, but has not been widely used for ALS research. Goal(s): We sought to investigate the utility of longitudinal MRI and MRS to assess the course of disease progression in an inducible TDP-43 mouse model of ALSApproach: T2, volume and NAA/tCr (N-acetyl aspartate/total creatine) were measured longitudinally in disease-relevant regions. Results: These metrics significantly changed in the 6-week induction phase of the model and reversed in the 6-week recovery phase, which was consistent with Amino-Cupric-Silver staining for degenerating neurons. NAA/tCr exhibited the greatest change: −29±14% at peak disease. Impact: We have demonstrated that T2 mapping, volumetric MRI, and MRS are sensitive to neuronal damage in a mouse model of ALS. These non-invasive endpoints therefore have the potential to be used clinically to monitor ALS progression and therapeutic efficacy.