Progressive brain volume alterations in the zQ175DN mouse model of Huntington’s Disease using in vivo MRI

Motivation: Robust translational imaging biomarkers are needed to facilitate the development of disease-modifying treatments for Huntington’s disease (HD), a rare inherited neurodegenerative disease. Goal(s): To determine the use of structural atrophy determined with MRI as a robust translational biomarker for testing therapeutics in mouse models prior to people with HD. Approach: In this work, we used semi-automatic delineations and tensor-based morphometry (TBM) of 3D high-resolution anatomical MR images to assess structural anomalies in the knock-in zQ175DN model of HD at different ages. Results: We detected progressive volumetric decrease in the zQ175DN mouse model, offering a powerful translational biomarker for the assessment of disease-modifying therapies. Impact: We report the first brain-wide structural study of zQ175DN mice using in vivo MRI. Our work supports structural atrophy as a robust translational biomarker for testing therapeutics in mouse models prior to people with HD.