Towards MRI axon radius mapping in clinical settings: insights from MRI-scale histology and experimental validation

Towards MRI axon radius mapping in clinical settings: insights from MRI-scale histology and experimental validation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Towards MRI axon radius mapping in clinical settings: insights from MRI-scale histology and experimental validation Laurin Mordhorst, Luke Edwards, Maria Morozova, Mohammad Ashtarayeh, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6114978/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The MRI-visible axon radius is a potential clinical biomarker for, e.g., neurological disorders. However, its clinical potential remains untapped, as in-vivo MRI-based estimation lacks validation in humans and currently requires specialized research scanners. Here, we assess state-of-the-art MRI methods for axon radius estimation against a new, open-access histological gold standard of two densely sampled human corpora callosa, enabling validation via quantitative spatial correlations. Our findings show a significant correlation between estimates from histology and in-vivo dMRI acquired with a research scanner. Critically, our simulations suggest that these findings can be translated from research to clinical scanners, enabling clinical adoption. We propose specific clinical scanner protocols and illustrate their potential in a hypothetical application distinguishing individuals with autism spectrum disorder from healthy controls. Overall, our study provides promising evidence for the validity of the MRI-visible axon radius and outlines a pathway to its clinical application, while critically discussing remaining challenges. Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging Health sciences/Anatomy/Nervous system/Brain Health sciences/Biomarkers/Diagnostic markers Biological sciences/Computational biology and bioinformatics/Image processing Biological sciences/Biological techniques/Microscopy/Transmission light microscopy diffusion-weighted MRI axon radius biomarker neurological disorders Full Text Additional Declarations There is NO Competing Interest. Supplementary Files supplementary.pdf Supplementary Information Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6114978","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":423461630,"identity":"86f7d0c5-bebc-4cc7-b499-176fdd1b459b","order_by":0,"name":"Laurin Mordhorst","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYBACPhCRAGGbgUl+MMmGWwsbuhYJyQZitDAgazE4QEgL+xmzDw93METzSx/e9uDjnro64/Or0yQYymxwa+HJMZ6ReIYhd2ZfWrnhjGeHJcxuvN1swHAuDY/DcowZEtsYcjec4TGT5jlwAKjl7MYHjG2HcWvhf4OipU7CeMbZDQcY2/7j1iKBaguzhAF/L8iWA3i0PCsGapHIndnDViY548BhyRk3eDcbJJxLxqmFnz95M+PPNpvcfh7mbRIfDtTx8/efBTLK7HBqgQIJZHYCPHKJBfwHSFM/CkbBKBgFwx4AABF3Tyym9LHAAAAAAElFTkSuQmCC","orcid":"","institution":"University of Luebeck","correspondingAuthor":true,"prefix":"","firstName":"Laurin","middleName":"","lastName":"Mordhorst","suffix":""},{"id":423461631,"identity":"dd45a8ee-688c-49e0-baa1-daa30a8ac433","order_by":1,"name":"Luke Edwards","email":"","orcid":"https://orcid.org/0000-0002-8320-7298","institution":"Max Planck Institute for Human Cognitive and Brain Sciences","correspondingAuthor":false,"prefix":"","firstName":"Luke","middleName":"","lastName":"Edwards","suffix":""},{"id":423461632,"identity":"7d3fee45-3aac-436b-b63a-849b62bff49b","order_by":2,"name":"Maria Morozova","email":"","orcid":"","institution":"Max Planck Institute for Human Cognitive and Brain Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Morozova","suffix":""},{"id":423461633,"identity":"3fdf6548-88d0-4fe1-9fcc-af1d159e06ba","order_by":3,"name":"Mohammad Ashtarayeh","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Ashtarayeh","suffix":""},{"id":423461634,"identity":"559feb02-1988-4b96-96b2-8b8153a45374","order_by":4,"name":"Tobias Streubel","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"Streubel","suffix":""},{"id":423461635,"identity":"dd4c6b86-f9c3-4167-8576-e2a65bb1df77","order_by":5,"name":"Björn Fricke","email":"","orcid":"","institution":"University of Luebeck","correspondingAuthor":false,"prefix":"","firstName":"Björn","middleName":"","lastName":"Fricke","suffix":""},{"id":423461636,"identity":"55ed30fa-ac00-41ed-89b4-3188a19de822","order_by":6,"name":"Francisco Fritz","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Francisco","middleName":"","lastName":"Fritz","suffix":""},{"id":423461637,"identity":"607f3113-7bcd-4e47-8ed8-a351e8b134e8","order_by":7,"name":"Henriette Rusch","email":"","orcid":"https://orcid.org/0000-0001-5989-5310","institution":"Paul Flechsig Institute - 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