{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T13:21:19Z","timestamp":1794057679009,"version":"4.8.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"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. Surg."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Emerging digital biopsy technologies, such as confocal laser endomicroscopy (CLE), have shown how neuro-oncological surgery can be revolutionised with the help of rapid, intraoperative tissue assessment which offers a high diagnostic accuracy. For <jats:italic>in vivo<\/jats:italic> CLE of cerebral neoplasia, there is only one existing staining agent\u2014Sodium-Fluorescein (SF)\u2014approved for intravenous application. The staining characteristics of SF yet remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In order to understand the dyeing behaviour of SF, we initiated a pilot study, comparing the staining pattern when incubating established tumour cell lines with SF <jats:italic>in vitro<\/jats:italic> to the distribution of intravenously applied SF <jats:italic>in situ<\/jats:italic>\u2014examined with CLE <jats:italic>ex vivo<\/jats:italic> as well <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, the cell lines showed a hyperbolic, time-dependent cellular accumulation of SF. Carcinoma cell lines showed significantly more intracellular SF than glioma cell lines. This phenomenon could be observed when applying SF intravenously before tumour resection surgery. In gliomas and meningiomas, SF could only be detected in 14.3% and 16.1% of images per case, while in carcinoma metastases, SF would accumulate in 68.1% of images per case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The concordant results from <jats:italic>in vitro<\/jats:italic>, <jats:italic>ex vivo<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> investigations could show that the cellular accumulation of the staining agent SF varies depending on the tumour entity. While primary brain tumours rarely show intracellular SF accumulation, carcinoma metastases display SF intracellularly more frequently. Therefore, SF allows for a better discrimination between brain tumours and brain metastases when performing CLE <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fsurg.2025.1567711","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:33:40Z","timestamp":1745818420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Fluorescein-distribution in confocal laser endomicroscopy allows for discrimination between primary brain tumours and metastases"],"prefix":"10.3389","volume":"12","author":[{"given":"Maria C.","family":"Brielmaier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Reifenrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Ganster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Pensel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Gempt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Schlegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"E9","DOI":"10.3171\/2022.3.Focus2250","article-title":"Real-time intraoperative surgical telepathology using confocal laser endomicroscopy","volume":"52","author":"Abramov","year":"2022","journal-title":"Neurosurg Focus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3390\/diagnostics11112128","article-title":"Socio-organizational impact of confocal Laser endomicroscopy in neurosurgery and neuropathology: results from a process analysis and expert survey","volume":"11","author":"Fotteler","year":"2021","journal-title":"Diagnostics (Basel"},{"key":"B3","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/neuonc\/noae006","article-title":"Fluorescein-stained confocal laser endomicroscopy versus conventional frozen section for intraoperative histopathological assessment of intracranial tumors","volume":"26","author":"Wagner","year":"2024","journal-title":"Neuro Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3389\/fonc.2019.00554","article-title":"Progress in confocal laser endomicroscopy for neurosurgery and technical nuances for brain tumor imaging with fluorescein","volume":"9","author":"Belykh","year":"2019","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s00701-012-1369-2","article-title":"Is it a glioblastoma? 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