Quantitative characterization of brain tissue damage in Huntington Disease using T1 normative atlas

Motivation: Quantification of brain tissue damage in Huntington disease (HD) is essential to design therapeutic strategies to prevent progression of neurodegeneration. Goal(s): To compare frequency and extent of deviations from normative ranges in pediatric-onset (POHD) and adult-onset HD (AOHD). Approach: Z-score maps of T1 relaxometry were estimated using a normative atlas accounting for age and sex. The distribution of abnormal voxels was compared between the two HD forms. Results: Striatal regions were severely damaged in both forms, but to a larger extent in POHD. POHD also showed higher z-scores in thalamus, midbrain, occipital and frontotemporal WM, and cerebellum, relatively spared in AOHD. Impact: Identification of specific regions of quantitative T1 abnormalities in different forms of Huntington disease may provide precious insights into pathophysiological mechanisms driving the different clinical presentations, as well as a promising biomarker to non-invasively monitor response to novel therapeutic strategies.