Abstract

Abstract BACKGROUND Extent of resection is a prognostic factor for low- and high-grade gliomas. Fluorescence guided surgery (FGS) using five-aminolevulinic acid (5-ALA) is associated with greater extent of resection in high-grade gliomas. However, for low-grade gliomas, intraoperative imaging technologies such as FGS, have not been optimized to distinguish tumor from normal tissue. Intraoperative confocal microscopy can better visualize tissue cytoarchitecture in real-time. Here we report on the feasibility of a newly-developed, hand-held, line-scanned dual-axis (LS-DAC) confocal microscope in distinguishing tumor vs. normal cells in ex vivo human low-grade glioma tissue. METHOD Ten low-grade glioma patients who underwent craniotomy were enrolled. Resected specimens were labelled with acridine orange (1mM) for one minute, and exposed surfaces were immediately imaged by our device. Subsequently, specimens were cut into sections and stained with H&E for histopathological analysis. RESULTS LS-DAC confocal microscope visualized nuclei of tumor cells vs. surrounding tissue, demonstrating clear differences in cellularity in the two compartments. Acquired images were comparable to those observed on matched H&E-stained sections. Live images provided minimal motion artifact due to the higher frame rate of 16 Hz. CONCLUSION LS-DAC confocal microscope provided real-time, high-contrast mosaic images of human low-grade glioma tissue ex vivo. The ability to distinguish tumor vs. normal tissue at the cellular level with little motion artifact, as well as the device’s hand-held design, suggests this technology merits additional investigation as an intraoperative adjunct for low-grade glioma surgery.

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