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

Authors

Evgenii Belykh
Liudmila Bardonova
Irakliy Abramov
Vadim A Byvaltsev
Talgat Kerymbayev
Kwanha Yu
Debbie R Healey
Ernesto Luna-Melendez
Benjamin Deneen
Shwetal Mehta
James K Liu
Mark C Preul

Publication Date

1-1-2023

Journal

Frontiers in Oncology

DOI

10.3389/fonc.2023.1156812

PMID

37287908

PMCID

PMC10242067

PubMedCentral® Posted Date

5-23-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

5-aminolevulinic acid, fluorescence guided surgery, fluorescein sodium, glioma, indocyanine green, laser scanning microscopy, protoporphyrin IX

Abstract

INTRODUCTION: Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

METHODS: Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an

RESULTS: Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of the normal brain. In low-grade gliomas, wide-field imaging cannot detect ICG staining, can detect FNa in only 50% of specimens, and is not sensitive enough for PpIX detection. With confocal imaging of low-intermediate grade glioma models, PpIX outperformed FNa.

DISCUSSION: Overall, compared to wide-field imaging, confocal microscopy significantly improved diagnostic accuracy and was better at detecting low concentrations of PpIX and FNa, resulting in improved tumor delineation. Neither PpIX, FNa, nor ICG delineated all tumor boundaries in studied tumor models, which emphasizes the need for novel visualization technologies and molecular probes to guide glioma resection. Simultaneous administration of 5-ALA and FNa with use of cellular-resolution imaging modalities may provide additional information for margin detection and may facilitate maximal glioma resection.