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Structural, microstructural, and neurochemical outcomes were assessed for sensitivity to change. Associations between change in MR and clinical and patient\u2010reported outcomes were evaluated. Sample sizes were estimated for preventive trials (at preataxic stage) and early\u2010stage trials using the most sensitive outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Infratentorial volumes, middle cerebellar peduncle (MCP) diffusivities and select neurochemical outcomes were more sensitive to change than SARA in both SCAs with moderate\u2010to\u2010high effect sizes (Cohen's\n                      <jats:italic>d<\/jats:italic>\n                      \u2265\u20090.5). The pons volume was the most sensitive outcome at both preataxic (\n                      <jats:italic>d\u2009=<\/jats:italic>\n                      \u20091.09) and ataxic (\n                      <jats:italic>d\u2009=<\/jats:italic>\n                      \u20091.48) stages. The most sensitive MR measures overlapped between genotypes, except that SCA1 showed faster progression in the cerebellum and SCA3 in the pons. Changes in MCP diffusivities and pontine neurochemical measures were associated with changes in SARA and FARS\u2010ADL (|\n                      <jats:italic>r<\/jats:italic>\n                      |\u2009=\u20090.28\u20130.47).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      The estimated sample sizes to detect a 50% reduction in progression with 80% power using the pons volume as primary outcome measure indicate the feasibility of preventive trials (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200973 per arm in a 1\u2010year trial) in common SCAs and predict a 6\u2010fold reduction in required sample sizes relative to SARA in early interventional trials. These findings support the use of MRI endpoints in early\u2010stage SCA trials.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70325","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T15:40:54Z","timestamp":1770738054000},"page":"1452-1466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Value of\n                    <scp>MRI<\/scp>\n                    Outcomes for Preventive and Early\u2010Stage Trials in Spinocerebellar Ataxias 1 and 3"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-0313","authenticated-orcid":false,"given":"Thiago J. 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