[Experimental study of detection of brain tumor at surgery using fluorescent imaging under a surgical microscope...

Total resection is the optimal treatment for malignant gliomas. However, we sometimes find an unexpected residual tumor mass on magnetic resonance imaging performed after an operation because of a macroscopically unclear margin of the tumor during operation. This study was designed to evaluate the effect of fluorescein sodium on imaging of glioma in combination with a surgical microscope for detection of the tumor at surgery in a rat glioma model. For this study, we produced two filters for the excitation and emission of fluorescein that can be easily fitted to and removed from a surgical microscope manually during the operation. For the in vivo study, Wistar rat brains bearing C6 glioma were removed at appropriate intervals after the intravenous administration of 10-20 mg/kg body weight of fluorescein sodium, and their surface and coronal sections through the tumor were observed using a surgical microscope with the filters. For the in vitro study, the cultured C6 glioma cells were exposed to 5 micrograms/ml of fluorescein sodium for 2 hours and then observed by confocal laser scanning microscopy. In the in vivo study, the C6 glioma itself and the brain within 2-3 mm of the gross surface of the tumor (probably indicating part of the perifocal edema) were well stained a brilliant yellowish green for a few hours. The normal brain was not stained. The intensity of the fluorescence was dose-dependent and was stronger under the xenon than under the halogen lamp. The in vitro study demonstrated almost no uptake of fluorescein by the C6 glioma cells. This fact indicates that the fluorescein in the stained tumor exists in extracellular spaces due to the disruption of the blood-brain barrier. These results suggest that this staining technique using fluorescein sodium and a surgical microscope with special filters during the operation may be the intravenous administration of 10 useful for detection of gliomas and warrants evaluation of clinical application.