Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas

Clinical article

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Object

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.

Methods

Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.

Results

Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.

Conclusions

Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.

Abbreviations used in this paper: 5-ALA = 5-aminolevulinic acid; BALANCE = Barrow ALA Intraoperative Confocal Evaluation; BNI = Barrow Neurological Institute; EOR = extent of resection; GTR = gross-total resection; HGG = high-grade glioma; LGG = low-grade glioma; NIHSS = National Institutes of Health Stroke Scale; ROI = region of interest.
Article Information

Contributor Notes

Address correspondence to: Nader Sanai, M.D., Division of Neurosurgical Oncology, Barrow Brain Tumor Research Center, Barrow Neurological Institute, 2910 North Third Avenue, Phoenix, Arizona 85013. email: nader.sanai@bnaneuro.net.Please include this information when citing this paper: published online July 15, 2011; DOI: 10.3171/2011.6.JNS11252.
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