{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:14:57Z","timestamp":1790604897443,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":186,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002108","name":"Friedreich\u2019s Ataxia Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"Friedreich\u2019s Ataxia Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Bob Allison Ataxia Research Center"},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["P41EB027061"],"award-info":[{"award-number":["P41EB027061"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["P30NS076408"],"award-info":[{"award-number":["P30NS076408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1S10OD017974"],"award-info":[{"award-number":["1S10OD017974"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Friedreich ataxia is a progressive neurodegenerative disorder characterized by cerebellar and spinal atrophy. However, studies to elucidate the longitudinal progression of the pathology in the brain are somewhat inconsistent and limited, especially for early-stage Friedreich ataxia. Using a multimodal neuroimaging protocol, combined with advanced analysis methods, we sought to identify macrostructural and microstructural alterations in the brain of patients with early-stage Friedreich ataxia to better understand its distribution patterns and progression. We enrolled 28 patients with Friedreich ataxia and 20 age- and gender-matched controls. Longitudinal clinical and imaging data were collected in the patients at baseline, 12, 24 and 36 months. Macrostructural differences were observed in patients with Friedreich ataxia, compared to controls, including lower volume of the cerebellar white matter (but not cerebellar grey matter), superior cerebellar peduncle, thalamus and brainstem structures, and higher volume of the fourth ventricle. Diffusion tensor imaging and fixel-based analysis metrics also showed microstructural differences in several brain regions, especially in the cerebellum and corticospinal tract. Over time, many of these macrostructural and microstructural alterations progressed, especially cerebellar grey and white matter volumes, and microstructure of the superior cerebellar peduncle, posterior limb of the internal capsule and superior corona radiata. In addition, linear regressions showed significant associations between many of those imaging metrics and clinical scales. This study provides evidence of early-stage macrostructural and microstructural alterations and of progression over time in the brain in Friedreich ataxia. Moreover, it allows to non-invasively map such brain alterations over a longer period (3 years) than any previous study, and identifies several brain regions with significant involvement in the disease progression besides the cerebellum. We show that fixel-based analysis of diffusion MRI data is particularly sensitive to longitudinal change in the cerebellar peduncles, as well as motor and sensory white matter tracts. In combination with other morphometric measures, they may therefore provide sensitive imaging biomarkers of disease progression for clinical trials.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad196","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T19:18:51Z","timestamp":1688671131000},"source":"Crossref","is-referenced-by-count":20,"title":["Brain MRI detects early-stage alterations and disease progression in Friedreich ataxia"],"prefix":"10.1093","volume":"5","author":[{"given":"Isaac M","family":"Adanyeguh","sequence":"first","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Joers","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9124-1955","authenticated-orcid":false,"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Iltis","sequence":"additional","affiliation":[{"name":"Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalaf O","family":"Bushara","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Minnesota Medical School , Minneapolis, MN 55455 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Gilles","family":"Henry","sequence":"additional","affiliation":[{"name":"Center for Magnetic 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