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Abstract #4029

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

Rohan S Virgincar1, Stephen Vito2, Man Kin Choy1, Becca Leahey2, William J Meilandt2, and Luke Xie1
1Translational Imaging, Genentech, South San Francisco, CA, United States, 2Neuroscience, Genentech, South San Francisco, CA, United States

Synopsis

Keywords: Other Neurodegeneration, Neurodegeneration, 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 ALS

Approach: 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.

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Keywords