Abstract

Fluorescence-guided surgery is one of the rapidly emerging methods of surgical "theranostics." In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies. Review of the literature. A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed. We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Highlights

  • Malignant glioma is a highly invasive, heterogeneous, complex, and fatal tumor type, the extent of which is not precisely identifiable by modern imaging techniques

  • Hansen initially showed that Indocyanine green (ICG) was able to highlight glioma tissue using an in vivo rat model [87], but therapeutically adequate doses did not produce sufficient fluorescence and required enhanced imaging technologies beyond the standard operating microscope [88, 89]

  • Acridine orange, and acriflavine are fluorescent dyes that were investigated for ex vivo use for rapid brain tumor tissue diagnosis using confocal endomicroscopy [64, 138]

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Summary

Introduction

Malignant glioma is a highly invasive, heterogeneous, complex, and fatal tumor type, the extent of which is not precisely identifiable by modern imaging techniques. Studied; hand-held confocal endomicroscope and LSM showed ICG selectively stained glioma cells in mouse model [66] Intraoperative administration at end of 5-ALA guided resection may show additional tumor tissue [67] BBB, blood–brain barrier; VEGF, vascular endothelial growth factor; EGFR, epidermal growth factor receptor; SERS, surface-enhanced Raman scattering, a nanoparticle tagging method to increase signal detection; FMI, fluorescence molecular imaging; BCS, breast cancer surgery; LSM, laser scanning microscope; VWCE, visible wavelength confocal endomicroscope (Optiscan 5.1) [71].

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