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Reduced dentate nucleus volume and increased mean magnetic susceptibility, a proxy of iron concentration, have been reported by magnetic resonance imaging studies in people with FRDA. Here, we investigate whether these changes are regionally heterogeneous.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Quantitative susceptibility mapping data were acquired from 49 people with FRDA and 46 healthy controls. The dentate nuclei were manually segmented and analyzed using three dimensional vertex\u2010based shape modeling and voxel\u2010based assessments to identify regional changes in morphometry and susceptibility, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Individuals with FRDA, relative to healthy controls, showed significant bilateral surface contraction most strongly at the rostral and caudal boundaries of the dentate nuclei. The magnitude of this surface contraction correlated with disease duration, and to a lesser extent, ataxia severity. Significantly greater susceptibility was also evident in the FRDA cohort relative to controls, but was instead localized to bilateral dorsomedial areas, and also correlated with disease duration and ataxia severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Changes in the structure of the dentate nuclei in FRDA are not spatially uniform. Atrophy is greatest in areas with high gray matter density, whereas increases in susceptibility\u2014reflecting iron concentration, demyelination, and\/or gliosis\u2014predominate in the medial white matter. These findings converge with established histological reports and indicate that regional measures of dentate nucleus substructure are more sensitive measures of disease expression than full\u2010structure averages. Biomarker development and therapeutic strategies that directly target the dentate nuclei, such as gene therapies, may be optimized by targeting these areas of maximal pathology. \u00a9 2024 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29816","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T03:39:40Z","timestamp":1713757180000},"page":"1109-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Localized Changes in Dentate Nucleus Shape and Magnetic Susceptibility in Friedreich Ataxia"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6843-9592","authenticated-orcid":false,"given":"Ian H.","family":"Harding","sequence":"first","affiliation":[{"name":"Department of Neuroscience Central Clinical School, Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ikhsan","family":"Nur Karim","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Central Clinical School, Monash University  Melbourne Australia"},{"name":"Faculty of Medicine Universitas Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa P.","family":"Selvadurai","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Central Clinical School, Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Corben","sequence":"additional","affiliation":[{"name":"Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute  Parkville Australia"},{"name":"Department of Pediatrics University of Melbourne  Parkville Australia"},{"name":"Turner Institute for Brain and Mental Health and School of Psychological Sciences Monash University  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin B.","family":"Delatycki","sequence":"additional","affiliation":[{"name":"Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute  Parkville Australia"},{"name":"Department of Pediatrics University of Melbourne  Parkville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Monti","sequence":"additional","affiliation":[{"name":"Institute of Biostructure and Bioimaging, National Research Council  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1323-6317","authenticated-orcid":false,"given":"Francesco","family":"Sacc\u00e0","sequence":"additional","affiliation":[{"name":"Neurosciences and Reproductive and Odontostomatological Sciences, University of Naples \u201cFederico II\u201d  Naples 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