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This prospective, longitudinal cohort study recruited children aged 8\u201316.99\u2009years with mTBI or mild orthopedic injury (OI) from five pediatric emergency departments. Children's pre\u2010injury and 1\u2010month post\u2010injury symptom ratings were used to classify mTBI with or without persistent symptoms. Children completed diffusion\u2010weighted imaging at post\u2010acute (2\u201333\u2009days post\u2010injury) and chronic (3 or 6\u00a0months via random assignment) post\u2010injury assessments. Mean diffusivity (MD) and fractional anisotropy (FA) were derived for 18 white matter tracts in 560 children (362 mTBI\/198 OI), 407 with longitudinal data. Superior longitudinal fasciculus FA was higher in mTBI without persistent symptoms relative to OI,<jats:italic>d<\/jats:italic>(95% confidence interval)\u00a0=\u00a00.31 to 0.37 (0.02, 0.68), across time. In younger children, MD of the anterior thalamic radiations was higher in mTBI with persistent symptoms relative to both mTBI without persistent symptoms, 1.43 (0.59, 2.27), and OI, 1.94 (1.07, 2.81). MD of the arcuate fasciculus, \u22120.58 (\u22121.04, \u22120.11), and superior longitudinal fasciculus, \u22120.49 (\u22120.90, \u22120.09) was lower in mTBI without persistent symptoms relative to OI at 6\u2009months post\u2010injury. White matter microstructural changes suggesting neuroinflammation and axonal swelling occurred chronically and continued 6\u2009months post injury in children with mTBI, especially in younger children with persistent symptoms, relative to OI. White matter microstructure appears more organized in children without persistent symptoms, consistent with their better clinical outcomes.<\/jats:p>","DOI":"10.1002\/hbm.25885","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T10:54:08Z","timestamp":1650884048000},"page":"3809-3823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Longitudinal white matter microstructural changes in pediatric mild traumatic brain injury: An<scp>A\u2010CAP<\/scp>study"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-4915","authenticated-orcid":false,"given":"Ashley L.","family":"Ware","sequence":"first","affiliation":[{"name":"Department of Psychology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"},{"name":"Department of Neurology University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith Owen","family":"Yeates","sequence":"additional","affiliation":[{"name":"Department of Psychology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Tang","sequence":"additional","affiliation":[{"name":"Independent Statistical Consulting Richmond British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayushi","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian I.","family":"Onicas","sequence":"additional","affiliation":[{"name":"Department of Psychology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"},{"name":"IMT School for Advanced Studies Lucca Lucca Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Psychology, Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Goodrich\u2010Hunsaker","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishard","family":"Abdeen","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Ottawa, Children's Hospital of Eastern Ontario Research Institute Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam H.","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Montreal &amp; CHU Sainte\u2010Justine Hospital Research Center Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Bjornson","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics University of British Columbia, Vancouver, BC, Canada; 2. 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