Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note

J Neurosurg. 2018 Feb;128(2):399-405. doi: 10.3171/2016.11.JNS161072. Epub 2017 Mar 24.

Abstract

OBJECTIVE Fluorescence guidance with 5-aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue. METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System). RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection. CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

Keywords: 5-ALA = 5–aminolevulinic acid; ALA; PPIX; PPIX = protoporphyrin IX; fluorescein; fluorescence-guided resection; malignant glioma; oncology.

MeSH terms

  • Aminolevulinic Acid
  • Brain Neoplasms / surgery*
  • Female
  • Fluorescein*
  • Fluorescence
  • Fluorescent Dyes*
  • Glioma / surgery*
  • Humans
  • Levulinic Acids*
  • Microscopy, Fluorescence
  • Neurosurgical Procedures / methods*
  • Photosensitizing Agents / pharmacology
  • Protoporphyrins / pharmacology
  • Surgery, Computer-Assisted / methods*
  • Treatment Outcome

Substances

  • Fluorescent Dyes
  • Levulinic Acids
  • Photosensitizing Agents
  • Protoporphyrins
  • protoporphyrin IX
  • Fluorescein