title: Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas.
abstract: OBJECTIVE
  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.
authors.affiliation: Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, Arizona 85013, USA. nader.sanai@bnaneuro.net
authors.forename: Nader
authors.initials: N
authors.lastname: Sanai
authors.forename: Laura A
authors.initials: LA
authors.lastname: Snyder
authors.forename: Norissa J
authors.initials: NJ
authors.lastname: Honea
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Coons
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Eschbacher
authors.forename: Kris A
authors.initials: KA
authors.lastname: Smith
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spetzler
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid; D001921:Brain / Q000601:surgery*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D038361:Neuronavigation; D017319:Photosensitizing Agents
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid