Quantitative Analysis of Blood to CSF Exchange over 24 Hours Following Intravenous Contrast MRI

Quantitative Analysis of Blood to CSF Exchange over 24 Hours Following Intravenous Contrast MRI | 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 Research Article Quantitative Analysis of Blood to CSF Exchange over 24 Hours Following Intravenous Contrast MRI Briana P Meyer, Lori A Ray, Taylor J Pedersen, Kevin A Carneiro, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8875356/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Background Impairment of the glymphatic system and brain solute clearance is associated with aging, traumatic brain injury, and neurodegenerative pathology, motivating efforts to quantify glymphatic transport in humans. Intrathecal contrast-enhanced MRI directly probes CSF–ISF exchange but has limited research applicability. Intravenous gadolinium-based contrast agents (GBCAs) are known to enter intracranial CSF, suggesting a complementary, less invasive strategy to probe brain fluid transport. Methods Hourly MRI data was acquired over a 24-hour period following IV GBCA administration in seven healthy adults. Quantitative T1 mapping was analyzed using linear mixed-effects models (LMMs) to test the effect of time across vascular, CSF, and brain compartments. A heavily T2-weighted inversion recovery sequence was included to improve identification of low concentration of GBCA in fluid compartments. Finally, pharmacokinetic compartment models were used to estimate transport between blood, CSF, and brain interstitial compartments. Results Quantitative MRI following intravenous GBCA administration indicates significant transport between the blood and subarachnoid space (SAS) (p < 0.001), with evidence for the involvement of the cerebral veins on hT2w-IR. In contrast, transport between the blood and ventricular CSF is comparatively limited (p = 0.923). Kinetic modeling further suggests that the SAS is not a single well-mixed compartment but best represented by both mobile regions and “sluggish” compartments. Conclusions Finally, exchange of GBCA into the brain interstitial space was not reliably detected, indicating that IV GBCA–based MRI is unlikely to provide a sensitive or specific measure of glymphatic CSF–ISF exchange. Together, these findings help refine the role of IV contrast MRI studies for quantifying solute transport in the human CNS and highlight important constraints on its use for assessing glymphatic function in humans. brain clearance MRI Blood-CSF-barrier IV Contrast Full Text Additional Declarations Competing interest reported. The authors J.J.I. and S.R.L. declare the existence of financial and incentive stock options competing interests. Supplementary Files 24hrManuscriptSupplementalData1MRI.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 12 May, 2026 Reviews received at journal 11 May, 2026 Reviews received at journal 23 Apr, 2026 Reviewers agreed at journal 21 Mar, 2026 Reviewers agreed at journal 23 Feb, 2026 Reviewers invited by journal 20 Feb, 2026 Editor assigned by journal 19 Feb, 2026 Submission checks completed at journal 19 Feb, 2026 First submitted to journal 13 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. We do this by developing innovative software and high quality services for the global research community. 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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-8875356","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":595657711,"identity":"35c2e1cf-513b-4ccd-9e13-82e3a5094a3c","order_by":0,"name":"Briana P Meyer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYBACAwbGBiBlw8MP5rIRryVNTrKBeC1gcNjY4ACxWsylDzd+Lqg5nLj5Ro4Bw4eyw4S1WPYlNkvPOJaeuA2ohXHGOSK0GJxhbJDmYbMGasndwMzbRpyW5t88/5gTN88AavlLpJY2ad42Z2MDCaAWRmK0WPYwtlnz9qXJSZx5/+Fgz7l0wlrMedgf3+b5BozK9rTEBz/KrAlrQQEHSFQ/CkbBKBgFowAXAAAY7TpI4nrpRAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Washington School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Briana","middleName":"P","lastName":"Meyer","suffix":""},{"id":595657712,"identity":"c3d8929c-febb-4054-b085-0727561a65f1","order_by":1,"name":"Lori A Ray","email":"","orcid":"","institution":"Montana State University","correspondingAuthor":false,"prefix":"","firstName":"Lori","middleName":"A","lastName":"Ray","suffix":""},{"id":595657713,"identity":"ca60ac3e-2877-4918-9340-b858a8ec220f","order_by":2,"name":"Taylor J Pedersen","email":"","orcid":"","institution":"Washington University in St. Louis","correspondingAuthor":false,"prefix":"","firstName":"Taylor","middleName":"J","lastName":"Pedersen","suffix":""},{"id":595657714,"identity":"d9d903fc-f16a-443e-a8eb-827da46e5b60","order_by":3,"name":"Kevin A Carneiro","email":"","orcid":"","institution":"University of North Carolina School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"A","lastName":"Carneiro","suffix":""},{"id":595657715,"identity":"80eae96c-c4af-4de7-9921-fe279222436f","order_by":4,"name":"Dawn Kernagis","email":"","orcid":"","institution":"Institute for Human and Machine Cognition","correspondingAuthor":false,"prefix":"","firstName":"Dawn","middleName":"","lastName":"Kernagis","suffix":""},{"id":595657716,"identity":"1c783dc7-c024-4019-ab5c-d14560f4bd3e","order_by":5,"name":"Rachael D Seidler","email":"","orcid":"","institution":"University of Florida","correspondingAuthor":false,"prefix":"","firstName":"Rachael","middleName":"D","lastName":"Seidler","suffix":""},{"id":595657717,"identity":"516a243a-43e5-4888-a5c2-bb08c27cfa29","order_by":6,"name":"Jeffery Hays","email":"","orcid":"","institution":"Montana State University","correspondingAuthor":false,"prefix":"","firstName":"Jeffery","middleName":"","lastName":"Hays","suffix":""},{"id":595657718,"identity":"7334e2cf-1bf8-4c9c-b346-9cb428ade48f","order_by":7,"name":"Jeffery J Iliff","email":"","orcid":"","institution":"University of Washington School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jeffery","middleName":"J","lastName":"Iliff","suffix":""},{"id":595657719,"identity":"1c718611-899e-47e9-986c-f99e9d980ae7","order_by":8,"name":"Swati Rane Levendovszky","email":"","orcid":"","institution":"University of Kansas Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Swati","middleName":"Rane","lastName":"Levendovszky","suffix":""}],"badges":[],"createdAt":"2026-02-13 20:53:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8875356/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8875356/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505874,"identity":"301b44e5-51cf-4e8c-879b-85ce4081ab3f","added_by":"auto","created_at":"2026-02-26 13:33:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1564506,"visible":true,"origin":"","legend":"","description":"","filename":"24hrManuscriptFBCNSInitialSubR1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8875356/v1_covered_c1e6f920-8191-48cf-8d97-2618d62dbf27.pdf"},{"id":103331126,"identity":"5263abc9-bee6-4c72-a5bb-5e118f5b1179","added_by":"auto","created_at":"2026-02-24 13:50:04","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1922681,"visible":true,"origin":"","legend":"","description":"","filename":"24hrManuscriptSupplementalData1MRI.docx","url":"https://assets-eu.researchsquare.com/files/rs-8875356/v1/b6771e20b601946c94a74cf9.docx"}],"financialInterests":"Competing interest reported. 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Intrathecal contrast-enhanced MRI directly probes CSF\u0026ndash;ISF exchange but has limited research applicability. Intravenous gadolinium-based contrast agents (GBCAs) are known to enter intracranial CSF, suggesting a complementary, less invasive strategy to probe brain fluid transport.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eHourly MRI data was acquired over a 24-hour period following IV GBCA administration in seven healthy adults. Quantitative T1 mapping was analyzed using linear mixed-effects models (LMMs) to test the effect of time across vascular, CSF, and brain compartments. A heavily T2-weighted inversion recovery sequence was included to improve identification of low concentration of GBCA in fluid compartments. Finally, pharmacokinetic compartment models were used to estimate transport between blood, CSF, and brain interstitial compartments.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eQuantitative MRI following intravenous GBCA administration indicates significant transport between the blood and subarachnoid space (SAS) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with evidence for the involvement of the cerebral veins on hT2w-IR. In contrast, transport between the blood and ventricular CSF is comparatively limited (p\u0026thinsp;=\u0026thinsp;0.923). Kinetic modeling further suggests that the SAS is not a single well-mixed compartment but best represented by both mobile regions and \u0026ldquo;sluggish\u0026rdquo; compartments.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFinally, exchange of GBCA into the brain interstitial space was not reliably detected, indicating that IV GBCA\u0026ndash;based MRI is unlikely to provide a sensitive or specific measure of glymphatic CSF\u0026ndash;ISF exchange. Together, these findings help refine the role of IV contrast MRI studies for quantifying solute transport in the human CNS and highlight important constraints on its use for assessing glymphatic function in humans.\u003c/p\u003e","manuscriptTitle":"Quantitative Analysis of Blood to CSF Exchange over 24 Hours Following Intravenous Contrast MRI","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-24 13:49:59","doi":"10.21203/rs.3.rs-8875356/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-12T06:40:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T21:42:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T06:56:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"27612557891816349408558507427884600076","date":"2026-03-21T19:58:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"231011320916608299449130478874412452006","date":"2026-02-23T12:47:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-20T10:41:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-19T13:52:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-19T08:54:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Fluids and Barriers of the CNS","date":"2026-02-13T20:47:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"fluids-and-barriers-of-the-cns","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"fbcn","sideBox":"Learn more about [Fluids and Barriers of the CNS](http://fluidsbarrierscns.biomedcentral.com/)","snPcode":"12987","submissionUrl":"https://submission.nature.com/new-submission/12987/3","title":"Fluids and Barriers of the CNS","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0ca09884-9590-46f6-bcc0-0d1cdd72d206","owner":[],"postedDate":"February 24th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-12T06:40:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T21:42:22+00:00","index":24,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T06:59:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-24 13:49:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8875356","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8875356","identity":"rs-8875356","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}