{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:58:44Z","timestamp":1790362724681,"version":"4.1.0"},"reference-count":34,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"39","funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["NS137950"],"award-info":[{"award-number":["NS137950"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["K12NS080223"],"award-info":[{"award-number":["K12NS080223"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["T32GM007863"],"award-info":[{"award-number":["T32GM007863"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["NCI P01 CA118816"],"award-info":[{"award-number":["NCI P01 CA118816"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010319","name":"Shurl and Kay Curci Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NINDS","award":["NS137950"],"award-info":[{"award-number":["NS137950"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ian\u2019s Friends Foundation","id":[{"id":"https:\/\/ror.org\/05d56bw89","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Chan Zuckerberg Foundation (CZI) Advancing Imaging","id":[{"id":"https:\/\/ror.org\/02qenvm24","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Cook Family Brain Tumor Research Fund"},{"name":"Mark Trauner Brain Research Fund"},{"name":"Mark Trauner Brain Research Fund"},{"name":"Zenkel Family Foundation"},{"name":"Zenkel Family Foundation"},{"name":"Resonance Philanthropies"},{"name":"UM Precision Health Investigators Awards grant program"},{"name":"Translational AI Award from the UM Department of Neurosurgery"},{"name":"UM Stanley and Judith Frankel Institute for Heart and Brain Health Innovative Multidisciplinary Research Pilot Award"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:p>\n                    A hallmark of glioblastoma (GBM) is disease recurrence that occurs in all patients despite resection, radiation, and chemotherapy. A critical challenge in GBM treatment is the management of recurrent disease for which no standard of care exists. Predicting the location of GBM recurrence may improve the efficiency of advanced-stage therapies. We present an artificial intelligence (AI)\u2013based model to predict the recurrence risk of unprocessed surgical tissues at initial resection. AI-informed label-free optical microscopy was used to generate a normalized tumor infiltration value (AI-infiltration) for optical images of samples taken from resection cavity margins. These values, in combination with clinical, radiographic, and molecular variables, were used to build a predictive model of focal recurrence. In a cohort of 80 patients, comprising 367 samples and 133,454 unique images, GBM infiltration was significantly higher in margin samples from recurrent sites (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u00a0= 0.03) compared with those from nonrecurrent sites. A random forest machine learning classifier predicted site recurrence with an average area under the receiver operating characteristic curve of 87%\u00a0\u00b1\u00a010.0 for the training cohort and 80% (95% confidence interval: 0.64 to 0.97) for the validation cohort. AI-infiltration was the strongest contributor to recurrence prediction, outperforming tumor molecular features. Model performance remained high regardless of tumor location, resulting in random forest model predictions of recurrence at 5 and 10 millimeters of each sample. These findings represent the potential of AI to predict sites of tumor recurrence, thereby improving accessibility to targeted, precision, and multimodal therapy for the highest-risk areas of disease.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec8202","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:58:53Z","timestamp":1790359133000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Optical microscopy predictions of focal recurrence in glioblastoma"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-2854","authenticated-orcid":true,"given":"Sanjeev","family":"Herr","sequence":"first","affiliation":[{"name":"Drexel University College of Medicine, Philadelphia, PA 19129, USA."},{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3698-454X","authenticated-orcid":true,"given":"Niels","family":"Olshausen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-8359","authenticated-orcid":true,"given":"Melike","family":"Pekmezci","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasleen","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0839-5428","authenticated-orcid":true,"given":"Youssef","family":"Sibih","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-9217","authenticated-orcid":true,"given":"Vardhaan","family":"Ambati","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-7011","authenticated-orcid":true,"given":"Abraham","family":"Dada","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Scotford","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Persad","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-6725","authenticated-orcid":true,"given":"Thiebaud","family":"Picart","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Kondepudi","sequence":"additional","affiliation":[{"name":"Machine Learning in Neurosurgery Laboratory, Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Malte","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Vulakh","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Pechmann","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Makolli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy Ann","family":"Oberheim-Bush","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."},{"name":"Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-8493","authenticated-orcid":true,"given":"Albert","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5499-4325","authenticated-orcid":true,"given":"Jacob","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1983-4892","authenticated-orcid":true,"given":"Mitchel S.","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-7330","authenticated-orcid":true,"given":"Ammar","family":"Mallouhi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-9831","authenticated-orcid":true,"given":"Barbara","family":"Kiesel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-0273","authenticated-orcid":true,"given":"Georg","family":"Widhalm","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-461X","authenticated-orcid":true,"given":"Lisa","family":"K\u00f6rner","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Vienna, Vienna, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0526","authenticated-orcid":true,"given":"Madhumita","family":"Sushil","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-6531","authenticated-orcid":true,"given":"Todd","family":"Hollon","sequence":"additional","affiliation":[{"name":"Machine Learning in Neurosurgery Laboratory, Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-260X","authenticated-orcid":true,"given":"Shawn L.","family":"Hervey-Jumper","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA."},{"name":"Weill Institute of Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac193"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.1373"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.6143"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad237"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-022-04039-y"},{"key":"e_1_3_2_7_2","first-page":"vdad169","article-title":"Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward","volume":"6","author":"Smith E. J.","year":"2024","unstructured":"E. J. Smith, A. Naik, M. Goel, P. Y. Wen, M. Lim, S. M. Chang, I. M. Germano, Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward. Neurooncol. Adv. 6, vdad169 (2024).","journal-title":"Neurooncol. Adv."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-012-0983-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/CCI.19.00121"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.24.3135"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/PAP.0b013e3182169934"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2013-0200-OA"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23403-5"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab0195"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-016-0027"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1165758"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3171\/2019.9.JNS192075"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91648-8"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02252-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0715-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaa162"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08169-3"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0000000000001202"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.16.16234"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/30604050"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.3857\/roj.2019.00017"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.01.033"},{"key":"e_1_3_2_28_2","first-page":"vdac006","article-title":"A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma","volume":"4","author":"Ramesh K.","year":"2022","unstructured":"K. Ramesh, E. A. Mellon, S. S. Gurbani, B. D. Weinberg, E. Schreibmann, S. A. Sheriff, M. Goryawala, M. de le Fuente, B. R. Eaton, J. Zhong, A. D. Voloschin, S. Sengupta, E. M. Dunbar, M. Holdhoff, P. B. Barker, A. A. Maudsley, L. R. Kleinberg, H. Shim, H. G. Shu, A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma. Neurooncol. Adv. 4, vdac006 (2022).","journal-title":"Neurooncol. Adv."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox175"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-020-03408-9"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3171\/2010.6.JNS091246"},{"key":"e_1_3_2_32_2","first-page":"364","article-title":"Safe surgery for glioblastoma: Recent advances and modern challenges","volume":"9","author":"Gerritsen J. K. W.","year":"2022","unstructured":"J. K. W. Gerritsen, M. L. D. Broekman, S. De Vleeschouwer, P. Schucht, B. V. Nahed, M. S. Berger, A. J. P. E. Vincent, Safe surgery for glioblastoma: Recent advances and modern challenges. Neurooncol. Pract. 9, 364\u2013379 (2022).","journal-title":"Neurooncol. Pract."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3171\/2014.7.JNS132449"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3171\/2014.6.JNS132038"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.52202\/068431-2066"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aec8202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:59:30Z","timestamp":1790359170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aec8202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":34,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2026,9,25]]}},"alternative-id":["10.1126\/sciadv.aec8202"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aec8202","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"2025-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec8202"}}