Identification of specific immune cells using fluorescence and digital histology in brain tumour operations

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An international team of researchers with significant involvement from the Department of Neurosurgery at Vienna General Hospital and MedUni Vienna has made significant progress in the visualisation of difficult-to-detect brain tumours during surgery. The recently published study is the first to investigate the combined use of 5-aminolevulinic acid (5-ALA) and digital stimulated Raman histology (SRH), a new type of microscopic fluorescence analysis tool. It has been shown for the first time that 5-ALA fluorescence can be used to identify not only tumour cells but also certain immune cells, which are an important part of the tumour microenvironment, in glioblastoma, the most common malignant primary brain tumour in adults.

Maximum safe surgical removal is crucial for the prognosis of patients with glioblastomas. However, due to infiltrative growth, where the tumour grows into healthy tissue, and the often poorly visible tumour margins during surgery, complete removal is difficult. Using the fluorescent marker 5-ALA, it is possible to visualise glioblastoma tissue under blue light during surgery. This innovative technique has enabled significantly improved visualisation and thus optimised removal of glioblastomas in recent years. The Department of Neurosurgery at MedUni Vienna and University Hospital Vienna is one of the world’s leading centres in the field of fluorescence diagnostics and research. However, it has so far remained unclear which cells actually accumulate this fluorescent dye.

The new laser-based SRH technology makes it possible to create high-resolution digital images of tissue samples taken during surgery on a microscopic level directly in the operating theatre. These two technologies, 5-ALA and SRH, were combined for the first time in a multi-centre study. The study, which involved the Department of Neurosurgery and the Division of Neuropathology and Neurochemistry at MedUni Vienna and University Hospital of Vienna as well as the Universities of Freiburg, Münster and New York University as part of the Comprehensive Center for Clinical Neurosciences and Mental Health, examined 115 patients with glioblastomas. It was shown that the combination of 5-ALA and SRH could be used successfully during tumour operations. The research team, led by Lisa Körner from the Department of Neurosurgery at MedUni Vienna and University Hospital Vienna, was thus able to visualise fluorescent cells at the microscopic level using SRH technology for the first time.

A particularly important study result with regard to future treatment options is that not only tumour cells, but also specific immune cells (especially tumour-associated macrophages), which are an important component of the tumour microenvironment, accumulate the fluorescent dye. This finding sheds new light on the immune microenvironment of glioblastomas, which could be of crucial importance for the treatment and progression of the disease.

The results of the study improve the understanding and interpretation of the 5-ALA fluorescence technique during glioblastoma surgery on a microscopic level for the first time. This should enable even more precise and personalised surgical removal of these tumours and improved visualisation of the immune microenvironment in the future. According to these findings, surgical resection could even change the immune environment of the tumour in a positive direction. The team from the Department of Neurosurgery at MedUni Vienna and University Hospital Vienna is planning further studies to investigate the precise impact of these findings on the improved surgical removal and treatment of glioblastomas.

Publication: Nature Biomedical Engineering

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy
Mustafa Nasir-Moin, Lisa Irina Wadiura (jetzige Körner), Vlad Sacalean, Devin Juros, Misha Movahed-Ezazi, Emily K. Lock, Andrew Smith, Matthew Lee, Hannah Weiss, Michael Müther, Daniel Alber, Sujay Ratna, Camila Fang, Eric Suero-Molina, Sönke Hellwig, Walter Stummer, Karl Rössler, Johannes A. Hainfellner, Georg Widhalm, Barbara Kiesel, David Reichert, Mario Mischkulnig, Rajan Jain, Jakob Straehle, Nicolas Neidert, Oliver Schnell, Jürgen Beck, Jay Trautman, Steve Pastore, Donato Pacione, Dimitris Placantonakis, Eric Karl Oermann, John G. Golfinos, Todd C. Hollon, Matija Snuder, Christian W. Freudiger, Dieter Henrik Heiland & Daniel A. Orringer
DOI: 10.1038/s41551’024 -01217-3