{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:16:40Z","timestamp":1786465000775,"version":"build-2736575974"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Biological brain aging can diverge substantially from chronological aging, particularly in chronic neurological conditions like multiple sclerosis (MS), where neuroinflammatory and neurodegenerative processes may accelerate age-related brain changes. This study aims to determine whether multipool Chemical Exchange Saturation Transfer (CEST) and T1 relaxometry at 7\u202fT can serve as biologically grounded imaging markers of brain age in healthy adults and people with MS (pwMS). BrainAgeMS (NCT06221631) is a prospective, single-center, cross-sectional comparative study recruiting 200 participants aged 18\u201365\u202fyears: 100 healthy controls (HC) and 100 pwMS. All participants undergo blood sampling for biological age determination using the PhenoAge algorithm, motor, cognitive, and psychological assessments, and 7\u202fT MRI featuring multipool CEST and T1 relaxometry. A brain age prediction model trained on HC data will be applied to pwMS to derive a brain age gap. The primary outcomes are the two brain-age gaps in pwMS: the differences between estimated brain age and (i) chronological age and (ii) PhenoAge. Secondary outcomes include associations of these gaps with disability, cognition, fatigue, and quality of life. If validated, these quantitative MRI markers could complement existing tools for MS disease monitoring and serve as outcome measures for future brain health interventions.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/study\/NCT06221631<\/jats:ext-link>\n                      , identifier NCT06221631\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1899641","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:01:51Z","timestamp":1786456911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BrainAgeMS: protocol for a prospective comparative study of brain aging in healthy adults and people with multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Sebasti\u00e1n","family":"Navarrete","sequence":"first","affiliation":[{"name":"Faculty of Engineering, Universidad de Concepci\u00f3n","place":["Concepci\u00f3n, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Capiglioni","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University of Bern","place":["Bern, Switzerland"]},{"name":"Translational Imaging Center (TIC), SITEM-INSEL","place":["Bern, Switzerland"]},{"name":"High-Field MR Center, Max Planck Institute for Biological Cybernetics","place":["T\u00fcbingen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Marti","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Pirpamer","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"McKinley","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hoepner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Le\u00f3n Betancourt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Radojewski","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging, Institute for Diagnostic and Interventional Neuroradiology, University of Bern","place":["Bern, Switzerland"]},{"name":"Translational Imaging Center (TIC), SITEM-INSEL","place":["Bern, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41586-018-0457-8","article-title":"Facing up to the global challenges of 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