Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics

Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics | 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 Method Article Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics Erick Hernandez-Gutierrez, Ricardo Coronado-Leija, Manon Edde, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7361397/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Mar, 2026 Read the published version in Brain Structure and Function → Version 1 posted 9 You are reading this latest preprint version Abstract Multiple sclerosis (MS) is a complex neuro-inflammatory disease characterized by heterogeneous lesion formation, demyelination, and axonal injury. Advanced neuroimaging techniques, particularly diffusion MRI (dMRI) and magnetization transfer imaging (MTI), provide sensitive biomarkers of microstructural changes. However, the high dimensionality and longitudinal nature of these datasets pose significant challenges for effective lesion analysis and visualization. We introduce five complementary visualization tools designed to integrate fixel-based multi-tensor, magnetization transfer, and free water metrics across multiple time points in MS patients. The framework supports patient-level, tract-specific, bundle-section, lesion-specific, and new arising lesions, facilitating both individual and cohort-wide investigations. We apply these tools to longitudinal datasets from multiple MS patients, analyzing microstructural changes in lesions, penumbra, and normal-appearing white matter (NAWM) over five scanning periods. The proposed framework reveals consistent spatial tissue gradients of microstructural disruption extending from lesions into penumbra and NAWM. It highlights substantial heterogeneity in lesion dynamics, where partial MTsat recovery was observed in a subset of lesions. Pre-lesional abnormalities in fixel-based fractional anisotropy (fixel-FA), radial diffusivity (fixel-RD), magnetization transfer saturation (MTsat), and isotropic volume fraction (MRDS-ISOVF) were consistently detected before new lesion appearance. Cohort-wide analysis confirmed the consistency of these patterns and underscored the importance of individualized lesion monitoring. This multi-metric longitudinal visualization framework enables exploration of multi-dimensional MS lesion data. By integrating advanced dMRI and MTI metrics, it supports different points of view of lesion heterogeneity, pre-lesional pathology, and tissue repair, offering valuable insights for disease monitoring. Diffusion MRI Multiple Sclerosis Multi-Tensor Tractography Longitudinal Visualization Magnetization Transfer Full Text Additional Declarations Competing interest reported. This research was partially funded by Imeka Solutions Inc., and Maxime Descoteaux has an affiliation or financial relationship with the company. Cite Share Download PDF Status: Published Journal Publication published 26 Mar, 2026 Read the published version in Brain Structure and Function → Version 1 posted Editorial decision: Revision requested 03 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 11 Sep, 2025 Reviews received at journal 04 Sep, 2025 Reviewers agreed at journal 28 Aug, 2025 Reviewers invited by journal 14 Aug, 2025 Editor assigned by journal 14 Aug, 2025 Submission checks completed at journal 13 Aug, 2025 First submitted to journal 13 Aug, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7361397","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Method Article","associatedPublications":[],"authors":[{"id":502828250,"identity":"e5a1cbba-741d-4346-bc91-ad5981000584","order_by":0,"name":"Erick Hernandez-Gutierrez","email":"data:image/png;base64,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","orcid":"","institution":"Université de Sherbrooke","correspondingAuthor":true,"prefix":"","firstName":"Erick","middleName":"","lastName":"Hernandez-Gutierrez","suffix":""},{"id":502828251,"identity":"548fb26d-867a-4b63-8dcd-efa1390d78a2","order_by":1,"name":"Ricardo Coronado-Leija","email":"","orcid":"","institution":"New York University","correspondingAuthor":false,"prefix":"","firstName":"Ricardo","middleName":"","lastName":"Coronado-Leija","suffix":""},{"id":502828252,"identity":"452a7fa9-cc18-40ce-b43c-b213411adff9","order_by":2,"name":"Manon Edde","email":"","orcid":"","institution":"Université de Sherbrooke","correspondingAuthor":false,"prefix":"","firstName":"Manon","middleName":"","lastName":"Edde","suffix":""},{"id":502828253,"identity":"403d7e0a-b78f-453d-9738-b04a31520870","order_by":3,"name":"François Rheault","email":"","orcid":"","institution":"Université de Sherbrooke","correspondingAuthor":false,"prefix":"","firstName":"François","middleName":"","lastName":"Rheault","suffix":""},{"id":502828254,"identity":"53681537-33bb-4ebc-9082-1dc791048a1f","order_by":4,"name":"Matthieu Dumont","email":"","orcid":"","institution":"Imeka Solutions Inc.","correspondingAuthor":false,"prefix":"","firstName":"Matthieu","middleName":"","lastName":"Dumont","suffix":""},{"id":502828255,"identity":"0384d686-3781-4c08-9090-0ea1d25fcbfb","order_by":5,"name":"Jean-Christophe Houde","email":"","orcid":"","institution":"Imeka Solutions Inc.","correspondingAuthor":false,"prefix":"","firstName":"Jean-Christophe","middleName":"","lastName":"Houde","suffix":""},{"id":502828256,"identity":"f6f63989-1d70-4806-aaef-4fcdeb251669","order_by":6,"name":"Muhamed Barakovic","email":"","orcid":"","institution":"Roche (Switzerland)","correspondingAuthor":false,"prefix":"","firstName":"Muhamed","middleName":"","lastName":"Barakovic","suffix":""},{"id":502828257,"identity":"ad246ba7-9c5b-41c9-85ec-b24cf55b2d0b","order_by":7,"name":"Stefano Magon","email":"","orcid":"","institution":"Roche (Switzerland)","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Magon","suffix":""},{"id":502828258,"identity":"ed39b3b8-8e21-44ff-bad9-eeb6f62f7c54","order_by":8,"name":"Alonso Ramirez-Manzanares","email":"","orcid":"","institution":"Mathematics Research Center","correspondingAuthor":false,"prefix":"","firstName":"Alonso","middleName":"","lastName":"Ramirez-Manzanares","suffix":""},{"id":502828259,"identity":"86b85310-bb8f-456a-ba4a-438457a7485c","order_by":9,"name":"Maxime Descoteaux","email":"","orcid":"","institution":"Université de Sherbrooke","correspondingAuthor":false,"prefix":"","firstName":"Maxime","middleName":"","lastName":"Descoteaux","suffix":""}],"badges":[],"createdAt":"2025-08-13 06:23:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7361397/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7361397/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00429-026-03094-9","type":"published","date":"2026-03-26T16:08:49+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":105755938,"identity":"9208fa2a-6a99-48d9-8f16-71591bfca197","added_by":"auto","created_at":"2026-03-30 16:33:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1349948,"visible":true,"origin":"","legend":"","description":"","filename":"hernandezgutierrezetal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7361397/v1_covered_d3edbd8c-9e73-4960-8666-73f26453b0e5.pdf"}],"financialInterests":"Competing interest reported. This research was partially funded by Imeka Solutions Inc., and Maxime Descoteaux has an affiliation or financial relationship with the company.","formattedTitle":"Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"brain-structure-and-function","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsaf","sideBox":"Learn more about [Brain Structure and Function](https://www.springer.com/journal/429)","snPcode":"429","submissionUrl":"https://submission.nature.com/new-submission/429/3","title":"Brain Structure and Function","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Diffusion MRI, Multiple Sclerosis, Multi-Tensor, Tractography, Longitudinal Visualization, Magnetization Transfer","lastPublishedDoi":"10.21203/rs.3.rs-7361397/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7361397/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Multiple sclerosis (MS) is a complex neuro-inflammatory disease characterized by heterogeneous lesion formation, demyelination, and axonal injury. Advanced neuroimaging techniques, particularly diffusion MRI (dMRI) and magnetization transfer imaging (MTI), provide sensitive biomarkers of microstructural changes. However, the high dimensionality and longitudinal nature of these datasets pose significant challenges for effective lesion analysis and visualization. We introduce five complementary visualization tools designed to integrate fixel-based multi-tensor, magnetization transfer, and free water metrics across multiple time points in MS patients. The framework supports patient-level, tract-specific, bundle-section, lesion-specific, and new arising lesions, facilitating both individual and cohort-wide investigations. We apply these tools to longitudinal datasets from multiple MS patients, analyzing microstructural changes in lesions, penumbra, and normal-appearing white matter (NAWM) over five scanning periods. The proposed framework reveals consistent spatial tissue gradients of microstructural disruption extending from lesions into penumbra and NAWM. It highlights substantial heterogeneity in lesion dynamics, where partial MTsat recovery was observed in a subset of lesions. Pre-lesional abnormalities in fixel-based fractional anisotropy (fixel-FA), radial diffusivity (fixel-RD), magnetization transfer saturation (MTsat), and isotropic volume fraction (MRDS-ISOVF) were consistently detected before new lesion appearance. Cohort-wide analysis confirmed the consistency of these patterns and underscored the importance of individualized lesion monitoring. This multi-metric longitudinal visualization framework enables exploration of multi-dimensional MS lesion data. By integrating advanced dMRI and MTI metrics, it supports different points of view of lesion heterogeneity, pre-lesional pathology, and tissue repair, offering valuable insights for disease monitoring.","manuscriptTitle":"Longitudinal Visualization Tools for Advanced Characterization of Multiple Sclerosis Lesions Using Diffusion MRI and Magnetization Transfer Imaging Metrics","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-22 06:22:22","doi":"10.21203/rs.3.rs-7361397/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-04T00:21:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T21:19:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306441034296507921942142266822261412641","date":"2025-09-12T01:17:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-04T11:20:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329341439969263819019076636969391705139","date":"2025-08-29T03:48:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-15T00:23:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-14T11:49:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-13T11:42:30+00:00","index":"","fulltext":""},{"type":"submitted","content":"Brain Structure and Function","date":"2025-08-13T06:12:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"brain-structure-and-function","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsaf","sideBox":"Learn more about [Brain Structure and Function](https://www.springer.com/journal/429)","snPcode":"429","submissionUrl":"https://submission.nature.com/new-submission/429/3","title":"Brain Structure and Function","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8351eff5-da97-4069-a183-cfe4dc7ff535","owner":[],"postedDate":"August 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T16:30:27+00:00","versionOfRecord":{"articleIdentity":"rs-7361397","link":"https://doi.org/10.1007/s00429-026-03094-9","journal":{"identity":"brain-structure-and-function","isVorOnly":false,"title":"Brain Structure and Function"},"publishedOn":"2026-03-26 16:08:49","publishedOnDateReadable":"March 26th, 2026"},"versionCreatedAt":"2025-08-22 06:22:22","video":"","vorDoi":"10.1007/s00429-026-03094-9","vorDoiUrl":"https://doi.org/10.1007/s00429-026-03094-9","workflowStages":[]},"version":"v1","identity":"rs-7361397","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7361397","identity":"rs-7361397","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}