Automated deformation analysis in the YAC128 Huntington disease mouse model

Abstract

The YAC128 mouse recapitulates many of the clinical features of Huntington disease (HD), including selective neuropathology with neuronal loss. Here we investigate whether differences in neuroanatomy could be detected using high-resolution magnetic resonance (MR) imaging earlier than the previously defined 9-month age of onset of striatal neuropathology. The striatum is significantly decreased in volume (3.4%, p<0.02) at 8 months of age. A subset of the brains was also analyzed using stereology, and the MR measures were found to be more robust at separating the two groups of mice. Striatal degeneration was found to be asymmetric, with the dorsal and lateral aspects of the striatum being most affected. Non-striatal changes in neuroanatomy were also investigated, revealing regions of expansion as well as atrophy. Our findings suggest that MR imaging can be used to detect and monitor subtle anatomical differences throughout the whole brain and at early time points in the YAC128 mouse-model of HD.