Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions

Abstract

IntroductionFluorescence-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.MethodsReview of the literature.ResultsA 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.ConclusionWe 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.

Probe-based three-dimensional confocal laser endomicroscopy of brain tumors: technical note

“…Future dyes or fluorescent probes that target tumors by more advanced and specific means will lead to further improvements in the use of 3D CLE technology to specifically examine tissue and guide or tailor resection. These dyes may include monoclonal antibodies against brain tumors bound to fluorescent molecules and other targeted fluorescent dyes 21–23…”

Weakly-Supervised Learning-Based Feature Localization for Confocal Laser Endomicroscopy Glioma Images

“…Rapid intraoperative interpretation of suspected brain tumor tissue is of paramount importance for planning the treatment and guiding the neurosurgeon towards the op-timal extent of tumor resection. Handheld, portable Confocal Laser Endomicroscopy (CLE) is being explored as a fluorescence imaging technique for its ability to image histopathological features of tissue at cellular resolution in real time during brain tumor surgery [1][2][3][4]. CLE systems can acquire up to 20 images per second, with areas in the tumor resection bed interrogated as an "optical biopsy".…”

A Fluorescence-Based Wireless Capsule Endoscopy System for Detecting Colorectal Cancer

“…The fluorescence intensity may vary depending on the region where the cancer is located, the time since it was injected, and on the fluorophore concentration. A fluorescein concentration of 5 mg/kg (~1.5 µM) to 20 mg/kg (~6 µM) is enough for detectable fluorescence emitting from the cancer cells when injected intravenously [38,39]. In this work, different concentrations of fluorescein were prepared (231 µM to 18 nM) in order to test whether the proposed capsule can detect different levels of fluorescence.…”