Digital Twin Model for Venovenous Extracorporeal Membrane Oxygenation Based on Pulse Physiology Engine

Digital Twin Model for Venovenous Extracorporeal Membrane Oxygenation Based on Pulse Physiology Engine | 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 Digital Twin Model for Venovenous Extracorporeal Membrane Oxygenation Based on Pulse Physiology Engine Rei Ukita, Jeffrey Webb, Sriya Bapatla, Yerin Woo, Andrew Kumpfbeck, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8982103/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a form of mechanical respiratory support therapy for patients with acute lung injury or end-stage lung disease. Clinical demand for VV-ECMO has increased substantially, yet consensus on optimal patient management strategies remains limited. ECMO physiology is highly complex and difficult to predict, given the three-way interactions between the patient, the mechanical ventilator, and the extracorporeal circuit. A physiological simulation platform would be a valuable tool for clinical decision support during ECMO, but currently available models have limited capability to simulate high-resolution transient responses. To fill this gap, we present a digital twin model of ECMO based on the Pulse Physiology Engine platform. The model was successfully validated using ten VV-ECMO patient datasets from a prior clinical study. Simulated transient venous oxygenation profiles closely matched measurements from an independent porcine VV-ECMO study. We present a representative simulation scenario that illustrates how VV-ECMO support enables titration and optimization of lung-protective ventilator settings. This digital twin model of VV-ECMO, based on the Pulse Physiology Engine, provides a foundation for future development of clinical decision-support tools and automated extracorporeal life-support technologies. Biological sciences/Biological techniques Health sciences/Diseases Physical sciences/Engineering Health sciences/Medical research Biological sciences/Physiology Full Text Additional Declarations Competing interest reported. R.U. and M.B. are inventors on a patent application US20250205468A1, "Smart programmable blood pump for controlling and automating extracorporeal life support applications." J.B.W., A.B., and R.C. are employees at Kitware, Inc. Supplementary Files SupplementaryInformation1.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 16 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 25 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 18 Mar, 2026 Editor assigned by journal 10 Mar, 2026 Submission checks completed at journal 04 Mar, 2026 First submitted to journal 03 Mar, 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-8982103","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":601898911,"identity":"fc822baa-c305-49e2-ba0c-2fd316dff8f2","order_by":0,"name":"Rei Ukita","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYFACxgYGhgMSDAzsDSRqkWDgOUCSTQcYJBgkEohUbN7e3MDMc8aijn/mGzOpGzUMcub9C/BrkTlzEKjlhoSExO0cM+mcYwzGMjce4NciIZEI1PIB6JfbaWnSuQ0MiTMkDhDQIv8QokX+5jFitUgwQhxmcIP5GEQLfwMBLTyJDQfnnJGQ3Hgm+bB1zjEJY6AbCWhhP/7wwZtjdfxyxw823s6psZGT4CfgMBBAVgK0gugIQgBibBkFo2AUjIIRBQBYHT5sVBmQqwAAAABJRU5ErkJggg==","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Rei","middleName":"","lastName":"Ukita","suffix":""},{"id":601898912,"identity":"18e57dcd-b325-44d6-85e6-42f72b2faeb8","order_by":1,"name":"Jeffrey Webb","email":"","orcid":"","institution":"Kitware (United States)","correspondingAuthor":false,"prefix":"","firstName":"Jeffrey","middleName":"","lastName":"Webb","suffix":""},{"id":601898913,"identity":"376ade05-900a-4553-a7fb-dcf20e22cca2","order_by":2,"name":"Sriya Bapatla","email":"","orcid":"","institution":"Vanderbilt University","correspondingAuthor":false,"prefix":"","firstName":"Sriya","middleName":"","lastName":"Bapatla","suffix":""},{"id":601898914,"identity":"28b9414f-c7c0-4c82-8561-1b629d3f01b3","order_by":3,"name":"Yerin Woo","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yerin","middleName":"","lastName":"Woo","suffix":""},{"id":601898915,"identity":"33c530f9-74b8-416d-a3bd-c861b940e9d7","order_by":4,"name":"Andrew Kumpfbeck","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Kumpfbeck","suffix":""},{"id":601898916,"identity":"6b191338-036f-483d-9d0f-8a7365379e9b","order_by":5,"name":"Aaron Bray","email":"","orcid":"","institution":"Kitware (United States)","correspondingAuthor":false,"prefix":"","firstName":"Aaron","middleName":"","lastName":"Bray","suffix":""},{"id":601898917,"identity":"1d2a6389-5e02-452a-8e25-a0f484e23d95","order_by":6,"name":"Matthew Bacchetta","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Bacchetta","suffix":""},{"id":601898918,"identity":"02734fd7-41f4-4197-93d0-2c292b79cfc1","order_by":7,"name":"Rachel Clipp","email":"","orcid":"","institution":"Kitware (United States)","correspondingAuthor":false,"prefix":"","firstName":"Rachel","middleName":"","lastName":"Clipp","suffix":""},{"id":601898919,"identity":"4d4b3add-2f71-4a51-a308-e443b8e8aa3c","order_by":8,"name":"Steve Keller","email":"","orcid":"","institution":"Johns Hopkins University","correspondingAuthor":false,"prefix":"","firstName":"Steve","middleName":"","lastName":"Keller","suffix":""}],"badges":[],"createdAt":"2026-02-27 00:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8982103/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8982103/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104405141,"identity":"6dceffc6-bcda-4ccc-a84e-13fa08ae82cf","added_by":"auto","created_at":"2026-03-11 12:21:55","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1850775,"visible":true,"origin":"","legend":"","description":"","filename":"jcystncgxyvgsbrhhhrfvftwtpszgxvb.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8982103/v1_covered_69754e36-f879-4d57-aba3-3e7ee3168a0b.pdf"},{"id":104333812,"identity":"68bc74cb-73f4-47ce-a479-8a9fcb5069d2","added_by":"auto","created_at":"2026-03-10 15:27:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":760583,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8982103/v1/68a23b39e9662a507f4885d3.pdf"}],"financialInterests":"Competing interest reported. R.U. and M.B. are inventors on a patent application US20250205468A1, \"Smart programmable blood pump for controlling and\nautomating extracorporeal life support applications.\" J.B.W., A.B., and R.C. are employees at Kitware, Inc.","formattedTitle":"Digital Twin Model for Venovenous Extracorporeal Membrane Oxygenation Based on Pulse Physiology Engine","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8982103/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8982103/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a form of mechanical respiratory support therapy for patients with acute lung injury or end-stage lung disease. Clinical demand for VV-ECMO has increased substantially, yet consensus on optimal patient management strategies remains limited. ECMO physiology is highly complex and difficult to predict, given the three-way interactions between the patient, the mechanical ventilator, and the extracorporeal circuit. A physiological simulation platform would be a valuable tool for clinical decision support during ECMO, but currently available models have limited capability to simulate high-resolution transient responses. To fill this gap, we present a digital twin model of ECMO based on the Pulse Physiology Engine platform. The model was successfully validated using ten VV-ECMO patient datasets from a prior clinical study. Simulated transient venous oxygenation profiles closely matched measurements from an independent porcine VV-ECMO study. We present a representative simulation scenario that illustrates how VV-ECMO support enables titration and optimization of lung-protective ventilator settings. This digital twin model of VV-ECMO, based on the Pulse Physiology Engine, provides a foundation for future development of clinical decision-support tools and automated extracorporeal life-support technologies.","manuscriptTitle":"Digital Twin Model for Venovenous Extracorporeal Membrane Oxygenation Based on Pulse Physiology Engine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-10 15:27:04","doi":"10.21203/rs.3.rs-8982103/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-16T18:42:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"237083317018145496042357495304743929529","date":"2026-04-16T16:39:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293428324972839489497670478891510514356","date":"2026-03-25T09:07:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21275421444762983822526461710758863734","date":"2026-03-18T14:30:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-18T14:23:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-10T17:24:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-04T09:27:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-03T19:46:31+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":"2229d2d5-ac8d-47f0-ae49-04649530ff18","owner":[],"postedDate":"March 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":64055502,"name":"Biological sciences/Biological techniques"},{"id":64055503,"name":"Health sciences/Diseases"},{"id":64055504,"name":"Physical sciences/Engineering"},{"id":64055505,"name":"Health sciences/Medical research"},{"id":64055506,"name":"Biological sciences/Physiology"}],"tags":[],"updatedAt":"2026-03-18T14:38:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-10 15:27:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8982103","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8982103","identity":"rs-8982103","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}