A Prospective Validation Study of the First 3D Digital Exoscope for Visualization of 5-ALA–Induced Fluorescence in High-Grade Gliomas

Background: We report on the first use of a digital 3-dimensional (3D) exoscope equipped with a 5-aminolevulinic acid (5-ALA) fluorescence visual system. Methods: We conducted a prospective clinical trial to evaluate the utility and sensitivity/specificity of the Olympus Orbeye 3D digital exoscope when used to visualize 5-ALA–induced fluorescence in patients with high-grade glioma undergoing a clinically indicated craniotomy. At least 2 tissue samples were each obtained from regions of strong, weak. and no fluorescence and evaluated in a blinded manner by a neuropathologist. Results: Twenty patients were enrolled. Intraoperative fluorescence was observed in 100% of subjects. One hundred twenty-one surgical specimens were collected for histopathological analysis; 40 with strong, 40 weak, and 41 with no visible fluorescence. Histopathology demonstrated 62.8% of samples (n = 76) contained abundant, 20.7% (n = 25) scarce, and 16.5% (n = 20) no tumor cells. Thirty-three of the 40 specimens (82.5%) in the strong fluorescence group correlated with abundant tumor cells and 7 (17.5%) with scarce. Twenty-nine of the 40 specimens (72.5%) in the weak fluorescence group correlated with abundant tumor cells, 7 (17.5%) with scarce, and 4 (10%) with none. Fourteen of the 41 (34.2%) specimens in the no fluorescence group had abundant tumor cells, 11 (26.8%) had scarce, and 16 (39%) had none. The sensitivity was 75% and specificity was 80%. The positive predictive value was 95% and negative predictive value was 39%. Conclusions: Visualization of 5-ALA–induced tumor fluorescence with use of the Orbeye 3D digital exoscope was feasible and associated with a high positive predictive value.