Intraoperative classification of glioblastoma through near real-time stimulated Raman scattering microscopy

Intraoperative classification of glioblastoma through near real-time stimulated Raman scattering microscopy | 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 Intraoperative classification of glioblastoma through near real-time stimulated Raman scattering microscopy Dieter Henrik Heiland, Jakob Straehle, Nicolas Neidert, Giulia Villa, and 30 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8232346/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Glioblastoma is a highly malignant brain tumor in which maximal safe resection is associated with improved survival, yet the oncological benefit of resection varies by molecular subtype. Recent work has shown that DNA methylation–defined subtypes, particularly receptor tyrosine kinase (RTK) I and II, benefit from complete CE (contrast-enriched) resection compared to mesenchymal tumors, highlighting the need for pre- or intraoperative tools that guide resection based on tumor biology. Here, we present iSTAMP (intraoperative Spatially-informed Tumor Architecture Mapping and Profiling) a real-time, label-free molecular classification framework using stimulated Raman scattering microscopy and graph-based deep learning to predict glioblastoma epigenetic subtypes intraoperatively (within 5-7 minutes). Across 1,295 intraoperative tissue samples from 236 patients profiled with EPIC methylation arrays, our graph attention network achieved high predictive performance for all major subtypes (AUC range 0.88–0.99), with spatially stable predictions across tumor regions. RTK subtypes, but not mesenchymal tumors, showed significant survival benefit from gross total resection (HR = 0.42, P = 6.1 × 10⁻⁶). Explainable AI methods revealed subtype-specific histopathological features, including necrosis and macrophage infiltration in mesenchymal tumors versus glio-fibrillary matrix or axon-rich regions in RTK tumors. Spatial transcriptomic validation confirmed cellular correlates with defined subtype specific SRH features. These findings support the integration of Raman-based molecular diagnostics into intraoperative workflows to guide biologically informed surgical strategies in glioblastoma. Health sciences/Neurology/Neurological disorders/CNS cancer Health sciences/Oncology/Cancer/CNS cancer Full Text Additional Declarations Yes there is potential Competing Interest. C. W. F. is affiliated with Invineo Inc.; however, this affiliation had no influence on the study design, data analysis, interpretation of results, or conclusions. Supplementary Files Supplementarytable1.csv Supplementary Table 1 Cite Share Download PDF Status: Under Review 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. 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-8232346","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":575621508,"identity":"2124c47b-dd0b-4411-beb1-96962493b75b","order_by":0,"name":"Dieter Henrik Heiland","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABYElEQVRIie2Rv2vCQBTH3xFIlrNZI1faf+GCYBGt+VcSApmiLRSKm5HATcGu+l/0D+hwcoOL7VxwEQpODoYu0krti9hi6A9wKyUfOO54fD+8d3cABQV/EEfbbgoXiYEIoEd4tJbg4qZFu5S7r9iYi3KKjsfyYJsi3ypcfiqgZQpkCqO/KWNtPEvv1MkZUzEnonGsG/ej6bkIwGSj3vPlS6MNhi/3FaV7vcF8U6n1vdglbwHVaduvt0QIZaywYT+4Ajp3cwq1YyqVdzshsSRC4V3CKmuJThcrESslyouskOcUM43XUnV3yobq5qLKaqIDDlZeS8kGlYtlvgu+lFQux4BLhKS6hV0IDsYpEYyuZNYl/8i6PUyksrMu3BM+KotKLXkIwJoQUS9FvifofH8wx1Sz5UqqUz4xnqxUNB3TDO3H1bUPZqKpKV03vRvDn8FPuF8qHz91COsD8wUFBQX/kHfocoByzRNWewAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-9258-3033","institution":"Friedrich-Alexander University Erlangen Nuremberg","correspondingAuthor":true,"prefix":"","firstName":"Dieter","middleName":"Henrik","lastName":"Heiland","suffix":""},{"id":575621509,"identity":"724d4f29-8225-4ae2-ba0a-6a2195319dfa","order_by":1,"name":"Jakob Straehle","email":"","orcid":"https://orcid.org/0000-0003-3063-8972","institution":"Department of Neurosurgery, Medical Center, University of Freiburg","correspondingAuthor":false,"prefix":"","firstName":"Jakob","middleName":"","lastName":"Straehle","suffix":""},{"id":575621510,"identity":"7bb1a974-75f3-41b0-a44e-b8818f6470d2","order_by":2,"name":"Nicolas Neidert","email":"","orcid":"https://orcid.org/0000-0003-0299-1138","institution":"Department of Neurosurgery, Medical Center, University of Freiburg","correspondingAuthor":false,"prefix":"","firstName":"Nicolas","middleName":"","lastName":"Neidert","suffix":""},{"id":575621511,"identity":"798c31c0-9270-46c7-8ab9-59881477d6b0","order_by":3,"name":"Giulia Villa","email":"","orcid":"","institution":"Translational Neurosurgery, Friedrich-Alexander Univesity Nuremberg-Erlangen","correspondingAuthor":false,"prefix":"","firstName":"Giulia","middleName":"","lastName":"Villa","suffix":""},{"id":575621513,"identity":"41d59ea8-27b7-40c7-9dd3-380c1e5bb5d9","order_by":4,"name":"Pierre Scheffler","email":"","orcid":"","institution":"Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Pierre","middleName":"","lastName":"Scheffler","suffix":""},{"id":575621516,"identity":"a5bcb769-1c91-4f41-89d2-29cfacd571c4","order_by":5,"name":"Zeynep Mercan","email":"","orcid":"","institution":"Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Zeynep","middleName":"","lastName":"Mercan","suffix":""},{"id":575621517,"identity":"cf078d36-8808-4163-bdee-936cad118bd2","order_by":6,"name":"David Reinecke","email":"","orcid":"","institution":"Department of General Neurosurgery, Center for Neurosurgery, University Hospital Cologne, Cologne, Germany","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Reinecke","suffix":""},{"id":575621518,"identity":"ae63f004-06ef-4cd0-bdfa-ef153c218033","order_by":7,"name":"Anna-Katharina Meissner","email":"","orcid":"","institution":"University of Cologne","correspondingAuthor":false,"prefix":"","firstName":"Anna-Katharina","middleName":"","lastName":"Meissner","suffix":""},{"id":575621519,"identity":"3681a7a2-da77-4e19-90a3-d4810bd41848","order_by":8,"name":"Abdulkader Al Shughri","email":"","orcid":"","institution":"Department of General Neurosurgery, Center for Neurosurgery, University Hospital Cologne, Cologne, Germany","correspondingAuthor":false,"prefix":"","firstName":"Abdulkader","middleName":"Al","lastName":"Shughri","suffix":""},{"id":575621520,"identity":"fe3e9f89-c4b3-4e44-a22b-59b90cb08a6f","order_by":9,"name":"Roland Goldbrunner","email":"","orcid":"","institution":"University Hospital Cologne","correspondingAuthor":false,"prefix":"","firstName":"Roland","middleName":"","lastName":"Goldbrunner","suffix":""},{"id":575621521,"identity":"88734806-4f9c-4e3c-9ca8-2dfb7bf957b5","order_by":10,"name":"Georg Widhalm","email":"","orcid":"https://orcid.org/0000-0001-6014-0273","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Georg","middleName":"","lastName":"Widhalm","suffix":""},{"id":575621522,"identity":"7031e715-f937-422a-9ef1-3a5f6e026b8e","order_by":11,"name":"Lisa Koerner","email":"","orcid":"https://orcid.org/0000-0002-9227-461X","institution":"Medical University Vienna","correspondingAuthor":false,"prefix":"","firstName":"Lisa","middleName":"","lastName":"Koerner","suffix":""},{"id":575621523,"identity":"791b10e5-fb01-462f-8963-4fb25cab02d9","order_by":12,"name":"Barbara Kiesel","email":"","orcid":"","institution":"Medical University Vienna","correspondingAuthor":false,"prefix":"","firstName":"Barbara","middleName":"","lastName":"Kiesel","suffix":""},{"id":575621524,"identity":"2ace40a5-0cd5-47a2-b2dc-0a3820f6bdae","order_by":13,"name":"Jessica Makolli","email":"","orcid":"","institution":"Department of Neurosurgery, Medical University of Vienna, Austria.","correspondingAuthor":false,"prefix":"","firstName":"Jessica","middleName":"","lastName":"Makolli","suffix":""},{"id":575621525,"identity":"fa3b0d79-78e6-4782-a8c4-02d57cddda71","order_by":14,"name":"Thomas Roetzer-Pejrimovsky","email":"","orcid":"https://orcid.org/0000-0001-8875-7304","institution":"Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Roetzer-Pejrimovsky","suffix":""},{"id":575621526,"identity":"9311108b-89ac-4dc2-a08c-4ade48d19939","order_by":15,"name":"Karl Rössler","email":"","orcid":"","institution":"Medical University Vienna","correspondingAuthor":false,"prefix":"","firstName":"Karl","middleName":"","lastName":"Rössler","suffix":""},{"id":575621527,"identity":"3ea9dc2c-8d1c-4401-9f09-ac5808077837","order_by":16,"name":"Lasse Dührsen","email":"","orcid":"","institution":"Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Lasse","middleName":"","lastName":"Dührsen","suffix":""},{"id":575621528,"identity":"d52b5990-88c9-4c53-a9e3-fce3fa356cd4","order_by":17,"name":"Ulrich Schüller","email":"","orcid":"https://orcid.org/0000-0002-8731-1121","institution":"University Medical Center, Hamburg-Eppendorf, Germany; Research Institute Children's Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Ulrich","middleName":"","lastName":"Schüller","suffix":""},{"id":575621529,"identity":"dd087b17-7e8a-4e22-a0cf-275ed26cb8fc","order_by":18,"name":"Richard Drexler","email":"","orcid":"","institution":"Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Richard","middleName":"","lastName":"Drexler","suffix":""},{"id":575621530,"identity":"e23a97fe-0bcd-409e-9510-194e811d11ef","order_by":19,"name":"Philipp Karschnia","email":"","orcid":"","institution":"Department of Neurosurgery, Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany","correspondingAuthor":false,"prefix":"","firstName":"Philipp","middleName":"","lastName":"Karschnia","suffix":""},{"id":575621531,"identity":"539fe030-0eae-46ae-8cdb-2a9ba9df1911","order_by":20,"name":"Adelheid Wöhrer","email":"","orcid":"","institution":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna","correspondingAuthor":false,"prefix":"","firstName":"Adelheid","middleName":"","lastName":"Wöhrer","suffix":""},{"id":575621532,"identity":"34d9c0d7-5b76-4211-9a3a-756cb5c34332","order_by":21,"name":"Christian Freyschlag","email":"","orcid":"","institution":"Department of Neurosurgery, Medical University of Innsbruck, Austria","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Freyschlag","suffix":""},{"id":575621533,"identity":"69e69011-62b0-4897-9092-00cdf448b7b6","order_by":22,"name":"Volker Coenen","email":"","orcid":"https://orcid.org/0000-0002-1703-6283","institution":"Department of Stereotactic and Functional Neurosurgery, Medical Center of Freiburg University, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Volker","middleName":"","lastName":"Coenen","suffix":""},{"id":575621534,"identity":"7b4c1508-2258-40a8-83c7-28333fe30ac6","order_by":23,"name":"Daniel Erny","email":"","orcid":"https://orcid.org/0000-0001-6000-8838","institution":"Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Erny","suffix":""},{"id":575621535,"identity":"ccdb0550-1863-452a-9216-f5630912c2b1","order_by":24,"name":"Roman Sankowski","email":"","orcid":"https://orcid.org/0000-0001-9215-8021","institution":"Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Roman","middleName":"","lastName":"Sankowski","suffix":""},{"id":575621536,"identity":"c58ddb15-563e-47f3-be7e-c7a128ab0c3e","order_by":25,"name":"Franz Ricklefs","email":"","orcid":"https://orcid.org/0000-0002-1321-6930","institution":"Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Franz","middleName":"","lastName":"Ricklefs","suffix":""},{"id":575621537,"identity":"b334d27a-2f51-432b-8eee-93e6615b8133","order_by":26,"name":"Roland Roelz","email":"","orcid":"","institution":"Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany","correspondingAuthor":false,"prefix":"","firstName":"Roland","middleName":"","lastName":"Roelz","suffix":""},{"id":575621538,"identity":"b8560f29-4aa5-48e4-a157-35361d8bb43e","order_by":27,"name":"Daniel Delev","email":"","orcid":"","institution":"Department of Neurosurgery, Uniklinikum Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Delev","suffix":""},{"id":575621541,"identity":"9132058c-af14-43d7-bd25-3c48e7524f06","order_by":28,"name":"Felix Sahm","email":"","orcid":"https://orcid.org/0000-0001-5441-1962","institution":"Department of Neuropathology, Heidelberg University Hospital, and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg","correspondingAuthor":false,"prefix":"","firstName":"Felix","middleName":"","lastName":"Sahm","suffix":""},{"id":575621543,"identity":"91cfedf7-820b-4746-887b-5ddf989b6c42","order_by":29,"name":"Oliver Schnell","email":"","orcid":"","institution":"Uniklinikum Erlangen","correspondingAuthor":false,"prefix":"","firstName":"Oliver","middleName":"","lastName":"Schnell","suffix":""},{"id":575621544,"identity":"8287d50e-5a3b-4cbe-be77-ff7f23856bb2","order_by":30,"name":"Marco Prinz","email":"","orcid":"https://orcid.org/0000-0002-0349-1955","institution":"Medical Center - University of Freiburg","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Prinz","suffix":""},{"id":575621545,"identity":"6918340a-8e8d-4072-a007-ba1c76f758c6","order_by":31,"name":"Christian Freudiger","email":"","orcid":"","institution":"Invenio","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"","lastName":"Freudiger","suffix":""},{"id":575621546,"identity":"e14a422f-3e57-4be0-aa75-bcd0e4cc08c2","order_by":32,"name":"Volker Neuschmelting","email":"","orcid":"https://orcid.org/0000-0001-7527-6990","institution":"University Hospital Cologne","correspondingAuthor":false,"prefix":"","firstName":"Volker","middleName":"","lastName":"Neuschmelting","suffix":""},{"id":575621547,"identity":"46438d5d-ecc9-4ca3-bf03-2ae0bec0c803","order_by":33,"name":"Jürgen Beck","email":"","orcid":"https://orcid.org/0000-0002-7687-6098","institution":"Neurosurgery Freiburg","correspondingAuthor":false,"prefix":"","firstName":"Jürgen","middleName":"","lastName":"Beck","suffix":""}],"badges":[],"createdAt":"2025-11-28 17:15:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8232346/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8232346/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100531152,"identity":"08f8a9cb-c7c9-4207-ac94-f9d48b985fa8","added_by":"auto","created_at":"2026-01-19 02:04:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3711951,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptV9.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8232346/v1/b8b49591dfdab021e4d4e1e2.pdf"},{"id":100548635,"identity":"cded5b67-d757-4afa-a13c-ea45b5ee6fa9","added_by":"auto","created_at":"2026-01-19 08:20:00","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":30910,"visible":true,"origin":"","legend":"","description":"","filename":"NCOMMS26001520T.json","url":"https://assets-eu.researchsquare.com/files/rs-8232346/v1/7a52b0fcdc1a889f8e376a1a.json"},{"id":100531151,"identity":"e4470b53-6dd1-4df4-976d-e06e04247006","added_by":"auto","created_at":"2026-01-19 02:04:36","extension":"csv","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":40974,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.csv","url":"https://assets-eu.researchsquare.com/files/rs-8232346/v1/dae7975350199e4c2407e174.csv"},{"id":100554577,"identity":"88035516-10f8-4249-86f4-32c1b1dc6f6f","added_by":"auto","created_at":"2026-01-19 08:38:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2134090,"visible":true,"origin":"","legend":"Article File","description":"","filename":"ManuscriptV9.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8232346/v1_covered_758d0e7c-dccb-466d-95c5-0b6d408d170f.pdf"},{"id":100531149,"identity":"2dfdc344-9c6b-495c-bcde-13e66009f8e6","added_by":"auto","created_at":"2026-01-19 02:04:36","extension":"csv","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40974,"visible":true,"origin":"","legend":"Supplementary Table 1","description":"","filename":"Supplementarytable1.csv","url":"https://assets-eu.researchsquare.com/files/rs-8232346/v1/39b31fe9f505d71966d8993f.csv"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nC. W. F. is affiliated with Invineo Inc.; however, this affiliation had no influence on the study design, data analysis, interpretation of results, or conclusions.","formattedTitle":"Intraoperative classification of glioblastoma through near real-time stimulated Raman scattering microscopy","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":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8232346/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8232346/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Glioblastoma is a highly malignant brain tumor in which maximal safe resection is associated with improved survival, yet the oncological benefit of resection varies by molecular subtype. Recent work has shown that DNA methylation–defined subtypes, particularly receptor tyrosine kinase (RTK) I and II, benefit from complete CE (contrast-enriched) resection compared to mesenchymal tumors, highlighting the need for pre- or intraoperative tools that guide resection based on tumor biology. Here, we present iSTAMP (intraoperative Spatially-informed Tumor Architecture Mapping and Profiling) a real-time, label-free molecular classification framework using stimulated Raman scattering microscopy and graph-based deep learning to predict glioblastoma epigenetic subtypes intraoperatively (within 5-7 minutes). Across 1,295 intraoperative tissue samples from 236 patients profiled with EPIC methylation arrays, our graph attention network achieved high predictive performance for all major subtypes (AUC range 0.88–0.99), with spatially stable predictions across tumor regions. RTK subtypes, but not mesenchymal tumors, showed significant survival benefit from gross total resection (HR = 0.42, P = 6.1 × 10⁻⁶). Explainable AI methods revealed subtype-specific histopathological features, including necrosis and macrophage infiltration in mesenchymal tumors versus glio-fibrillary matrix or axon-rich regions in RTK tumors. Spatial transcriptomic validation confirmed cellular correlates with defined subtype specific SRH features. These findings support the integration of Raman-based molecular diagnostics into intraoperative workflows to guide biologically informed surgical strategies in glioblastoma.","manuscriptTitle":"Intraoperative classification of glioblastoma through near real-time stimulated Raman scattering microscopy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 02:04:31","doi":"10.21203/rs.3.rs-8232346/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8d17c493-d9e3-4c5f-ae33-15d323c85831","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":61248897,"name":"Health sciences/Neurology/Neurological disorders/CNS cancer"},{"id":61248898,"name":"Health sciences/Oncology/Cancer/CNS cancer"}],"tags":[],"updatedAt":"2026-03-02T11:51:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 02:04:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8232346","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8232346","identity":"rs-8232346","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}