Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma

Evgenii Belykh, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Neurosurgery, Irkutsk State Medical University, Irkutsk, Russia.Follow
Eric J. Miller, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Danying Hu, Biorobotics Laboratory, Department of Electrical Engineering, University of Washington, Seattle, Washington, USA.
Nikolay L. Martirosyan, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.Follow
Eric C. Woolf, Department of Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Adrienne C. Scheck, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Vadim A. Byvaltsev, Department of Neurosurgery, Irkutsk State Medical University, Irkutsk, Russia.
Peter Nakaji, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Leonard Y. Nelson, Human Photonics Laboratory, Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA.
Eric J. Seibel, Human Photonics Laboratory, Department of Mechanical Engineering, University of Washington, Seattle, Washington, USA.
Mark C. Preul, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address: Neuropub@barrowneuro.org.

Document Type

Article

Abstract

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)

Publication Date

5-1-2018

Publication Title

World neurosurgery

E-ISSN

1878-8769

Volume

113

First Page

e51

Last Page

e69

PubMed ID

29408716

Digital Object Identifier (DOI)

10.1016/j.wneu.2018.01.151

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