{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:11:19Z","timestamp":1753891879746,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Glioblastoma is the most common type of primary brain malignancy and has a poor prognosis. The standard treatment strategy is based on maximal safe surgical resection followed by radiotherapy and chemotherapy. Surgical resection can be optimized by using 5-delta-aminolevulinic acid (5-ALA)\u2013induced fluorescence, which is the current mainstay. Although 5-ALA\u2013induced fluorescence has gained general acceptance, it is also limited by inter-observer variability and non-standardized fluorescence parameters. We present a new software for processing images analysis to better recognize the tumor infiltration margins using an intraoperative immediate safety map of 5-ALA\u2013induced fluorescence. We tested this in a brain model using a commercial surgical exoscope.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A dedicated software GLIOVIS (ACQuF-II, Advanced Colorimetry-based Quantification of Fluorescence) was designed for processing analysis of images taken on the Intraoperative Orbital Camera Olympus Orbeye (IOC) to determine the relative quantification of Protoporphyrin IX (5-ALA metabolite) fluorescence. The software allows to superpose the new fluorescence intensity map and the safety margins over the original images. The software was tested on gel-based brain models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two surrogate models were developed: PpIX agarose gel\u2013integrated in gelatin-based brain model at different scales (1:25 and 1:1). The images taken with the IOC were then processed using GLIOVIS. The intensity map and safety margins could be obtained for all available models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GLIOVIS for 5-ALA\u2013guided surgery image processing was validated on various gelatin-based brain models. Different levels of fluorescence could be qualitatively digitalized using this technique. These results need to be further confirmed and corroborated <jats:italic>in vivo<\/jats:italic> and validated clinically in order to define a new standard of care for glioblastoma resection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1361022","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T04:36:52Z","timestamp":1714365412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Automated online safety margin (GLIOVIS) for glioma surgery model"],"prefix":"10.3389","volume":"14","author":[{"given":"Marianne","family":"Mazevet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Oberli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Marinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismail","family":"Zaed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Kaelin-Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Marchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Gardenghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Reinert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Cardia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/op.22.00476","article-title":"Key clinical principles in the management of glioblastoma","volume":"19","author":"Kotecha","year":"2023","journal-title":"JCO Oncol Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.99.3.0467","article-title":"Survival following surgery and prognostic factors for recently diagnosed Malignant glioma: Data from the glioma outcomes project","volume":"99","author":"Laws","year":"2003","journal-title":"J Neurosurg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3171\/2008.4.17536","article-title":"Independent association of extent of resection with survival in patients with Malignant brain astrocytoma: Clinical article","volume":"110","author":"McGirt","year":"2009","journal-title":"J Neurosurg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01569","article-title":"The impact of surgery in IDH 1 wild type glioblastoma in relation with the MGMT deregulation","volume":"9","author":"Marchi","year":"2020","journal-title":"Front Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10143-023-02064-7","article-title":"Resection of the contrast-enhancing tumor in diffuse gliomas bordering eloquent areas using electrophysiology and 5-ALA fluorescence: evaluation of resection rates and neurological outcome\u2014a systematic review and meta-analysis","volume":"46","author":"Peters","year":"2023","journal-title":"Neurosurg Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac255","article-title":"Impact of maximal extent of resection on postoperative deficits, patient functioning, and survival within clinically important glioblastoma subgroups","volume":"25","author":"Gerritsen","year":"2023","journal-title":"Neuro Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1001\/jamaoncol.2016.1373","article-title":"Association of the extent of resection with survival in glioblastoma","volume":"2","author":"Brown","year":"2016","journal-title":"JAMA Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.01.26","article-title":"Fluorescence-guided surgery in cancer treatment: current status and future perspectives","volume":"7","author":"Zheng","year":"2019","journal-title":"Ann Transl Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1586\/14737140.2016.1121109","article-title":"Current status and future perspectives of fluorescence-guided surgery for cancer","volume":"16","author":"Delong","year":"2016","journal-title":"Expert Rev Anticancer Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1156812","article-title":"5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades","volume":"13","author":"Belykh","year":"2023","journal-title":"Front Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00314","article-title":"Fluorescence-guided surgery","volume":"7","author":"Nagaya","year":"2017","journal-title":"Front Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03098-y","article-title":"5-ALA and FDA approval for glioma surgery","volume":"141","author":"Hadjipanayis","year":"2019","journal-title":"J Neurooncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-016-3028-5","article-title":"Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results","volume":"159","author":"Senders","year":"2017","journal-title":"Acta Neurochir. (Wien)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/J.WNEU.2013.06.014","article-title":"Intraoperative fluorescence-guided resection of high-grade gliomas: A comparison of the present techniques and evolution of future strategies","volume":"82","author":"Li","year":"2014","journal-title":"World Neurosurg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.2010.00799.x","article-title":"5-aminolevulinic acid-induced protoporphyrin IX levels in tissue of human Malignant brain tumors","volume":"86","author":"Johansson","year":"2010","journal-title":"Photochem Photobiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac193","article-title":"Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group","volume":"25","author":"Karschnia","year":"2023","journal-title":"Neuro Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1001\/jamaoncol.2019.6143","article-title":"Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma","volume":"6","author":"Molinaro","year":"2020","journal-title":"JAMA Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03098-y.5-ALA","article-title":"5-ALA and FDA approved for glimoa surgery","volume":"141","author":"Hadjipanayis","year":"2017","journal-title":"Physiol Behav"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0000000000000929","article-title":"What is the surgical benefit of utilizing 5-aminolevulinic acid for fluorescence-guided surgery of Malignant gliomas","volume":"77","author":"Hadjipanayis","year":"2015","journal-title":"Neurosurgery"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac191","article-title":"Turning on the light for brain tumor surgery: A 5-aminolevulinic acid story","volume":"24","author":"McCracken","year":"2022","journal-title":"Neuro Oncol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.wneu.2021.02.118","article-title":"5-aminolevulinic acid\u2013shedding light on where to focus","volume":"150","author":"Dadario","year":"2021","journal-title":"World Neurosurg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3171\/2014.12.JNS14391","article-title":"Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery","volume":"123","author":"Vald\u00e9s","year":"2015","journal-title":"J Neurosurg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s11060-017-2474-0","article-title":"Epithelial growth factor receptor expression influences 5-ALA induced glioblastoma fluorescence","volume":"133","author":"Fontana","year":"2017","journal-title":"J Neurooncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2019.00041","article-title":"Quantitative modulation of PpiX fluorescence and improved glioma visualization","volume":"6","author":"Reinert","year":"2019","journal-title":"Front Surg"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2020.00014","article-title":"Corrigendum: quantitative modulation of ppIX fluorescence and improved glioma visualization","volume":"7","author":"Reinert","year":"2020","journal-title":"Front Surg"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1364\/ol.38.002786","article-title":"System and methods for wide-field quantitative fluorescence imaging during neurosurgery","volume":"38","author":"Valdes","year":"2013","journal-title":"Opt Lett"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3171\/2011.2.JNS101451","article-title":"Quantitative fluorescence in intracranial tumor: Implications for ALA-induced PpIX as an intraoperative biomarker - Clinical article","volume":"115","author":"Vald\u00e9s","year":"2011","journal-title":"J Neurosurg"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1361022\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T04:36:54Z","timestamp":1714365414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2024.1361022\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":28,"alternative-id":["10.3389\/fonc.2024.1361022"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2024.1361022","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2024,4,29]]},"article-number":"1361022"}}