Dual labeling with 5-aminolevulinic acid and fluorescein in high-grade glioma surgery with a prototype filter system built into a neurosurgical microscope: technical note

J Neurosurg. 2019 Apr 26;132(6):1724-1730. doi: 10.3171/2018.12.JNS182422.

Abstract

Objective: Recent efforts to improve visualization of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence resulted in a dual-labeling technique, combining it with fluorescein sodium in a prototype setup. Fluorescein identifies regions with blood-brain barrier breakdown in gliomas. However, normally perfused and edematous brain fluoresces unselectively, with strong background enhancement. The aim of this study was to test the feasibility of a novel, integrated filter combination using porphyrins for selective tumor identification and fluorescein for background enhancement.

Methods: A microscope with a novel built-in filter system (YB 475) for visualizing both fluorescein and 5-ALA-induced porphyrins was used. Resection limits were identified with the conventional BLUE 400 filter system. Six patients harboring contrast ring-enhancing lesions were analyzed.

Results: The complete surgical field could now be illuminated. Fluorescein was helpful for improving background visualization, and enhancing dura, edematous tissue, and cortex. Overlapping regions with both fluorophores harbored merged orange fluorescence. PPIX fluorescence was better visualized, even in areas beyond a normal working distance of approximately 25 cm, where the BLUE 400 filters recognized no or weak fluorescence.

Conclusions: The novel filter system improved general tissue brightness and background visualization, enhancing fluorescence-guided tumor resection. Furthermore, it appears promising from a scientific perspective, enabling the simultaneous and direct observation of areas with blood-brain barrier breakdown and PPIX fluorescence.

Keywords: ALA; diagnostic technique; dual labeling; fluorescein; high-grade glioma; oncology; protoporphyrin IX.