The shape of things to come. Mapping spatiotemporal progression of striatal morphology in Huntington disease: The IMAGE-HD study.

Mapping the spatiotemporal progression of neuroanatomical change in Huntington's Disease (HD) is fundamental to the development of bio-measures for prognostication. Statistical shape analysis to measure the striatum has been performed in HD, however there have been a limited number of longitudinal studies. To address these limitations, we utilised the Spherical Harmonic Point Distribution Method (SPHARM-PDM) to generate point distribution models of the striatum in individuals, and used linear mixed models to test for localised shape change over time in pre-manifest HD (pre-HD), symp-HD (symp-HD) and control individuals. Longitudinal MRI scans from the IMAGE-HD study were used (baseline, 18 and 30 months). We found significant differences in the shape of the striatum between groups. Significant group-by-time interaction was observed for the putamen bilaterally, but not for caudate. A differential rate of shape change between groups over time was observed, with more significant deflation in the symp-HD group in comparison with the pre-HD and control groups. CAG repeats were correlated with bilateral striatal shape in pre-HD and symp-HD. Robust statistical analysis of the correlates of striatal shape change in HD has confirmed the suitability of striatal morphology as a potential biomarker correlated with CAG-repeat length, and potentially, an endophenotype.

Competing Interests: Declaration of Competing Interest J.C. Stout has received funding from CHDI Foundation unrelated to this research. She is also director of Zindametrix Pty Ltd., which has research contracts supporting the implementation of cognitive assessments in HD clinical trials, none of which are relevant to this research. J.C.L. Looi self-funded travel and computer infrastructure costs to coordinate this research through the Australian United States Scandinavian-Spanish Imaging Exchange (AUSSIE), based at the Australian National University Medical School. M. Walterfang has received funding for research from and has received honoraria from Actelion, Vtesse and Biomarin pharmaceuticals, unrelated to this research.

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