Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.

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Purpose: Develop focal stereotactic proton irradiation for accurate spatial localization (< 2mm) in the rodent brain. Planning and evaluation was performed using Micro‐Computed Tomography (CT) and magnetic resonance spectroscopy (MRS). Method and Materials: Rodents were visualized using Micro‐CT; the data was transferred to Optirad (proton treatment planning system) for planning the site of brain irradiation (20 Gy). After irradiation the animals were positioned for proton magnetic resonance spectroscopy (MRS) on a 4.7T imager. Acquisition conditions for metabolite assessment allowed complete relaxation between excitations. A 5 mm3 voxel was placed at the irradiation site. Care was taken to avoid bone‐tissue interfaces. The MRS data was collected into 2048 points (frequency resolution of 1.2 Hz/point), a relaxation delay of 4s and an echo time of 120ms. A water presupression pulse reduced the water peak below 1%. The MRS acquisition parameters were; a field of view of 5 cm, two acquisitions, a matrix size of 256 × 128 for a total imaging time of 8.5min. Results: At 12 hrs after focal irradiation, MRS revealed the presence of a lactate (Lac) peak that did not resolve during the course of the 5‐day imaging series. In addition, the peak height of N‐acetyl‐aspartate (NAA) was reduced at 12 hrs compared to choline (Cho) and creatine (Cre) peaks. The NAA changes relative to Cho/Cre appeared to resolve over the 5 day time course. Conclusion: Focal stereotactic proton irradiation (<2mm) can be obtained when combined with CT and MRS. Validation of high dose focal irradiation by MRS suggested cellular injury as evidenced by a persistent lactate peak, indicative that cellular necrosis continues for at least five days. Transient neuronal injury was shown by reduced NAA/(Cho+Cre) at 12h with a partial recovery over the next five days. Histology was performed to further validate these findings.