MR-based skull parametric modeling for blood-brain barrier opening in non-human primates

MR-based skull parametric modeling for blood-brain barrier opening in non-human primates | 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 MR-based skull parametric modeling for blood-brain barrier opening in non-human primates Sergio Jiménez Gambín, Fotios Tsitsos, Sua Bae, Robin Ji, Elisa E. Konofagou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8801186/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Focused ultrasound (FUS) transcranial procedures require of simulation planning using the computed tomography (CT) of the skull, leading to ionizing radiation. Zero echo time (ZTE) magnetic resonance imaging (MRI) is a safe alternative for blood-brain barrier opening (BBBO) planning in non-human primates (NHP), as it provides good contrast for bone imaging. In this study, we applied a classical coordinate-to-coordinate linear-regression method to obtain the ZTE-to-CT relationship for six NHP skulls. First, we compared ZTE-based (pseudo-CT/pCT) and CT-based simulations ex-vivo, with differences of 2.39±0.49%, 3.65±0.52%, 0.49±0.00 mm and 0.00±0.00 mm for the focal volume, attenuation, axial and lateral shifts, respectively. The differences between pCT simulations and experiments were 2.53±1.33%, 1.74±0.57 mm and 0.30±0.11 mm for the focal attenuation, axial and lateral shifts, respectively. Finally, pCT-based and CT-based simulations for in-vivo planning resulted in differences of 3.39±3.09%, 6.04±1.34%, 2.05±1.40% and 0.71±0.16 mm for the focal volume, attenuation, in-focus BBBO volume, and sonicated skull thickness, respectively, where pCT and CT predicted a 49.12±11.05% and 47.06±12.17% of BBBO volume, respectively. These results demonstrate for the first time the feasibility of a ZTE-to-CT skull modeling method for BBBOplanning in NHPs, defining a safe and non-ionizing technique for skull acquisition in transcranial FUS applications. Health sciences/Health care Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience focused ultrasound blood-brain barrier skull modeling magnetic resonance imaging computed tomography Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementalMultimedia.mov Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 22 Apr, 2026 Reviews received at journal 14 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviews received at journal 05 Mar, 2026 Reviewers agreed at journal 28 Feb, 2026 Reviewers agreed at journal 27 Feb, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviewers invited by journal 26 Feb, 2026 Editor assigned by journal 26 Feb, 2026 Editor invited by journal 26 Feb, 2026 Submission checks completed at journal 24 Feb, 2026 First submitted to journal 24 Feb, 2026 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. 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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-8801186","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":598685482,"identity":"e1cedaa9-cdf7-4aa0-b510-eedfbdcefb00","order_by":0,"name":"Sergio Jiménez Gambín","email":"","orcid":"","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Sergio","middleName":"Jiménez","lastName":"Gambín","suffix":""},{"id":598685483,"identity":"0180fc4b-1301-4a79-97d8-bf8a07d6d301","order_by":1,"name":"Fotios Tsitsos","email":"","orcid":"","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Fotios","middleName":"","lastName":"Tsitsos","suffix":""},{"id":598685484,"identity":"a5fef679-862b-407e-a816-0e4ba9ca0479","order_by":2,"name":"Sua Bae","email":"","orcid":"","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Sua","middleName":"","lastName":"Bae","suffix":""},{"id":598685485,"identity":"9426519d-ce15-413e-9f5c-e67daabc0cda","order_by":3,"name":"Robin Ji","email":"","orcid":"","institution":"Columbia University","correspondingAuthor":false,"prefix":"","firstName":"Robin","middleName":"","lastName":"Ji","suffix":""},{"id":598685486,"identity":"7ff01af3-faa0-4e01-b48f-61e4ada9f9fa","order_by":4,"name":"Elisa E. 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Zero echo time (ZTE) magnetic resonance imaging (MRI) is a safe alternative for blood-brain barrier opening (BBBO) planning in non-human primates (NHP), as it provides good contrast for bone imaging. In this study, we applied a classical coordinate-to-coordinate linear-regression method to obtain the ZTE-to-CT relationship for six NHP skulls. First, we compared ZTE-based (pseudo-CT/pCT) and CT-based simulations ex-vivo, with differences of 2.39±0.49%, 3.65±0.52%, 0.49±0.00 mm and 0.00±0.00 mm for the focal volume, attenuation, axial and lateral shifts, respectively. The differences between pCT simulations and experiments were 2.53±1.33%, 1.74±0.57 mm and 0.30±0.11 mm for the focal attenuation, axial and lateral shifts, respectively. Finally, pCT-based and CT-based simulations for in-vivo planning resulted in differences of 3.39±3.09%, 6.04±1.34%, 2.05±1.40% and 0.71±0.16 mm for the focal volume, attenuation, in-focus BBBO volume, and sonicated skull thickness, respectively, where pCT and CT predicted a 49.12±11.05% and 47.06±12.17% of BBBO volume, respectively. These results demonstrate for the first time the feasibility of a ZTE-to-CT skull modeling method for BBBOplanning in NHPs, defining a safe and non-ionizing technique for skull acquisition in transcranial FUS applications.","manuscriptTitle":"MR-based skull parametric modeling for blood-brain barrier opening in non-human primates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-04 12:52:35","doi":"10.21203/rs.3.rs-8801186/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-22T10:27:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-15T03:45:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-10T03:59:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T21:32:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"234762847443445916884602484166825931645","date":"2026-03-01T02:35:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"206882790005047520344166429275396185697","date":"2026-02-27T11:31:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"225029231528922416276292222638502496479","date":"2026-02-26T17:41:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-26T17:27:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-26T17:26:30+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-26T17:22:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-24T20:11:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-24T20:07:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2b28403d-7f82-4ecc-a054-528126f7f373","owner":[],"postedDate":"March 4th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":63710791,"name":"Health sciences/Health care"},{"id":63710792,"name":"Health sciences/Medical research"},{"id":63710793,"name":"Health sciences/Neurology"},{"id":63710794,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-04-22T10:40:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-04 12:52:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8801186","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8801186","identity":"rs-8801186","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}