gms | German Medical Science

Objective: Fluorescence-guidance with 5-Aminolevulinic Acid (5-ALA) has been approved for malignant glioma surgery by the European Medicine Agencies (EMA) in Europe and the Food and Drug Administration (FDA) in the USA. Multiple systems have since been developed for visualizing fluorescing Protoporphyrin IX (PPIX). Employing such systems for fluorescence-guided resections implicitly assumes that qualitative fluorescence detection is equivalent to the established standard tested in a randomized setting and approved by EMA and FDA. This assumption needs to be critically assessed. Goal of this study was to define a threshold of fluorescent tissue discrimination under the BLUE400 filter-system (Carl Zeiss Meditec, Oberkochen, Germany), based on the expressed concentration of PPIX (cPPIX) in tumor tissue.

Methods: Utilizing a hyperspectral imaging system, tumor samples from patients harboring different tumor tissues were analyzed. Absolute values of cPPIX were calculated after calibrating the system with fluorescence phantoms with known cPPIX.

Results: 524 samples from 162 patients harboring different tumor types were analyzed. Visual fluorescence under the BLUE400 filter was documented by the attending neurosurgeon. A 0.9 µg/ml threshold of cPPIX could be defined as the minimal concentration required to detect and discriminate visual fluorescence.

Conclusion: The current generation of fluorescence microscopes enables fluorescence discrimination in tumor tissue with a threshold of cPPIX of 0.9 µg/ml, thus defining specificity and sensitivity of this technology as initially tested in a randomized trial. Novel technologies should show similar characteristics in order to be used safely and effectively. If more sensitive, such technologies require further assessments of tumor selectivity.