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The objectives are to determine fornix DTI age relationships in healthy controls and characterize DTI deviations in MS. High-resolution, fluid-suppressed DTI tractography quantified fornix volume and DTI parameters (fractional anisotropy - FA; mean, axial, radial diffusivity - MD, AD, RD) in 103 healthy controls (12\u201365 years) and 42 MS participants (13\u201363 years). Other brain volumes were measured on T1-weighted MPRAGE. All parameters were assessed for age trajectories, compared between groups, and correlated to clinical\/cognitive assessments in MS. Control fornix volume increased markedly (~1.7x) from 12 to 33 years and then declined to a similar extent by 65 years, while MD, AD, and RD showed U-shaped changes with minima ~30\u201333 years; conversely, FA showed no age relationship. MS fornix volume followed a similar age trend, but remained below controls at all ages and was proportionally reduced (-29%) more than all other brain volumes. In contrast, age relationships of MD, AD, and RD were lost due to similarly higher diffusivity in MS over all ages and FA was below controls across all ages. MS fornix volume\/diffusion metrics correlated with various clinical\/cognitive scores. Fluid-suppressed, high-resolution diffusion tractography showed nonlinear changes of the fornix in controls over the observed lifespan and early deviations in MS, consistent across age, suggesting it is an early target of injury.<\/jats:p>","DOI":"10.1162\/imag.a.1186","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T20:01:55Z","timestamp":1773345715000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":0,"title":["High-resolution fluid-suppressed diffusion tractography of the fornix across the healthy lifespan and deviations in multiple sclerosis"],"prefix":"10.1162","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8331-7044","authenticated-orcid":false,"given":"Carly","family":"Weber","sequence":"first","affiliation":[{"name":"Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-4577","authenticated-orcid":false,"given":"Penelope","family":"Smyth","sequence":"additional","affiliation":[{"name":"Neurology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4598-2672","authenticated-orcid":false,"given":"Gregg","family":"Blevins","sequence":"additional","affiliation":[{"name":"Neurology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4853-4047","authenticated-orcid":false,"given":"Colin","family":"Wilbur","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2678-3077","authenticated-orcid":false,"given":"Derek","family":"Emery","sequence":"additional","affiliation":[{"name":"Radiology and Diagnostic Imaging, University of Alberta, Edmonton Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-3298","authenticated-orcid":false,"given":"Christian","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Radiology and Diagnostic Imaging, University of Alberta, Edmonton Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"281","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"issue":"2","key":"2026033015560140500_IMAG.a.1186-b1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuroimage.2011.03.025","article-title":"Regional brain atrophy in children with multiple sclerosis","volume":"58","author":"Aubert-Broche","year":"2011","journal-title":"NeuroImage"},{"issue":"7","key":"2026033015560140500_IMAG.a.1186-b2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1177\/1352458519829698","article-title":"Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure","volume":"25","author":"Bartels","year":"2019","journal-title":"Multiple Sclerosis Journal"},{"key":"2026033015560140500_IMAG.a.1186-b3","doi-asserted-by":"crossref","first-page":"665017","DOI":"10.3389\/fnins.2021.665017","article-title":"Modern technology in multi-shell diffusion MRI reveals diffuse white matter changes in young adults with relapsing-remitting multiple sclerosis","volume":"15","author":"Beaudoin","year":"2021","journal-title":"Frontiers in Neuroscience"},{"issue":"7","key":"2026033015560140500_IMAG.a.1186-b4","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1089\/brain.2020.0749","article-title":"Dissecting the fornix in basic memory processes and neuropsychiatric disease: A review","volume":"10","author":"Benear","year":"2020","journal-title":"Brain Connectivity"},{"issue":"2","key":"2026033015560140500_IMAG.a.1186-b5","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1037\/1040-3590.8.2.145","article-title":"Revision of the brief visuospatial memory test: Studies of normal performance, reliability, and validity","volume":"8","author":"Benedict","year":"1996","journal-title":"Psychological Assessment"},{"issue":"2","key":"2026033015560140500_IMAG.a.1186-b6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1212\/WNL.0000000000002237","article-title":"White and gray matter damage in primary progressive MS: The chicken or the egg?","volume":"86","author":"Bodini","year":"2016","journal-title":"Neurology"},{"key":"2026033015560140500_IMAG.a.1186-b7","doi-asserted-by":"crossref","DOI":"10.1007\/b97636","volume-title":"Model selection and multimodel inference","author":"Burnham","year":"2004"},{"key":"2026033015560140500_IMAG.a.1186-b8","unstructured":"Concha, L., Gross, D. 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