Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma
OBJECTIVE: Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). METHODS: 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. RESULTS: SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. CONCLUSIONS: SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes.
Medical Subject Headings
Administration, Oral; Aminolevulinic Acid (administration & dosage, pharmacokinetics); Animals; Biotransformation; Brain Neoplasms (chemistry, diagnostic imaging, pathology); Cell Line, Tumor; Female; Fiber Optic Technology (instrumentation); Fluorescent Dyes (analysis); Genes, Reporter; Glioma (chemistry, diagnostic imaging, pathology); Mice; Mice, Inbred C57BL; Microscopy, Confocal (instrumentation, methods); Microscopy, Fluorescence (instrumentation, methods); Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Transplantation; Neuroendoscopes; Neuroendoscopy (instrumentation, methods); Photobleaching; Photosensitizing Agents (analysis); Protoporphyrins (analysis, biosynthesis); Single-Cell Analysis; Surgery, Computer-Assisted (instrumentation, methods)
Digital Object Identifier (DOI)
Belykh, Evgenii; Miller, Eric J.; Hu, Danying; Martirosyan, Nikolay L.; Woolf, Eric C.; Scheck, Adrienne C.; Byvaltsev, Vadim A.; Nakaji, Peter; Nelson, Leonard Y.; Seibel, Eric J.; and Preul, Mark C., "Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma" (2018). Neurosurgery. 1717.