Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

Journal

Nature biomedical engineering

ISSN: 2157-846X

Titre abrégé: Nat Biomed Eng

Pays: England

ID NLM: 101696896

Informations de publication

Date de publication:
10 Jul 2024

Historique:

received: 03 04 2022

accepted: 20 04 2024

medline: 11 7 2024

pubmed: 11 7 2024

entrez: 10 7 2024

Statut: aheadofprint

Résumé

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Identifiants

DOI: 10.1038/s41551-024-01217-3 PMID: 38987630

pubmed: 38987630

doi: 10.1038/s41551-024-01217-3

pii: 10.1038/s41551-024-01217-3

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

ID : R01-CA226527

Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)

ID : K12NS080223

Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)

ID : J 4725-B

Informations de copyright

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