{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:23:53Z","timestamp":1787603033562,"version":"build-2736575974"},"reference-count":50,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":222,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Volumetric MRI of the caudate and putamen is a robust biomarker of striatal degeneration in Huntington\u2019s disease (HD). Striatal degeneration may be reflected beyond volume alone, in additional shape and intensity alterations. We evaluated five novel morphometric biomarkers of the caudate and putamen\u2014curvature, flatness, eccentricity, elongation, and focal assessment of divergence estimation (FADE; T1-weighted signal shift)\u2014using cross-sectional and longitudinal MRI data from healthy controls (N = 100), individuals with premanifest HD (preHD; N = 100), and individuals with early manifest HD (earlyHD; N = 100). Geometric measures showed significant cross-sectional group differences with large effect sizes, although volume remained the most sensitive individual biomarker. Longitudinally, most geometric measures detected abnormal rates of change, particularly in the caudate, with medium-to-large effect sizes. The direct comparison between preHD and earlyHD proved challenging for all biomarkers; however, elongation yielded the largest effect size and outperformed volume in this comparison. FADE detected abnormal signal increases in HD groups at baseline but not longitudinally. Power analyses confirmed that volume retains the highest sensitivity, while geometric measures follow closely. Combining volume and geometric measures improved the cross-validated classification accuracy starting at low sample sizes. Correlations between scores and results from atrophy simulations confirmed that HD leaves two signatures on the striatum: loss of volume and loss of shape. While volume remains the strongest standalone biomarker, geometric measures provide complementary information that sharpens disease detection and may enhance biomarker frameworks in future HD clinical trials.<\/jats:p>","DOI":"10.1162\/imag.a.1351","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:01:56Z","timestamp":1786478516000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":0,"title":["Geometric properties of caudate and putamen mark the progression of Huntington\u2019s disease"],"prefix":"10.1162","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2834-7220","authenticated-orcid":false,"given":"Dorian","family":"Pustina","sequence":"first","affiliation":[{"name":"CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc., Princeton, NJ, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1907-788X","authenticated-orcid":false,"given":"Haikel","family":"Bogale","sequence":"additional","affiliation":[{"name":"Rancho BioSciences, Rancho Santa Fe, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhitsu","family":"Das","sequence":"additional","affiliation":[{"name":"Paid consultant, Rancho BioSciences, Rancho Santa Fe, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4212-3362","authenticated-orcid":false,"given":"Brian","family":"Avants","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Sathe","sequence":"additional","affiliation":[{"name":"CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc., Princeton, NJ, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sampaio","sequence":"additional","affiliation":[{"name":"CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc., Princeton, NJ, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wood","sequence":"additional","affiliation":[{"name":"CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc., Princeton, NJ, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"281","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026082415553112000_IMAG.a.1351-b1","first-page":"101","article-title":"The shape operator for differential analysis of images","volume":"18","author":"Avants","year":"2003","journal-title":"Inf Process Med Imaging"},{"issue":"11","key":"2026082415553112000_IMAG.a.1351-b2","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/mds.26013","article-title":"Magnetic resonance imaging striatal volumes: A biomarker for clinical trials in Huntington\u2019s disease","volume":"29","author":"Aylward","year":"2014","journal-title":"Mov Disord"},{"issue":"1","key":"2026082415553112000_IMAG.a.1351-b3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1212\/01.WNL.0000132965.14653.D1","article-title":"Onset and rate of striatal atrophy in preclinical Huntington disease","volume":"63","author":"Aylward","year":"2004","journal-title":"Neurology"},{"key":"2026082415553112000_IMAG.a.1351-b4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society. 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