title: Miniaturized handheld confocal microscopy for neurosurgery: results in an experimental glioblastoma model.
abstract: BACKGROUND
  Recent developments in optical science and image processing have miniaturized the components required for confocal microscopy. Clinical confocal imaging applications have emerged, including assessment of colonic mucosal dysplasia during colonoscopy. We present our initial experience with handheld, miniaturized confocal imaging in a murine brain tumor model.
  
  
  METHODS
  Twelve C57/BL6 mice were implanted intracranially with 10(5) GL261 glioblastoma cells. The brains of 6 anesthetized mice each at 14 and 21 days after implantation were exposed surgically, and the brain surface was imaged using a handheld confocal probe affixed to a stereotactic frame. The probe was moved systematically over regions of normal and tumor-containing tissue. Intravenous fluorescein and topical acriflavine contrast agents were used. Biopsies were obtained at each imaging site beneath the probe and assessed histologically. Mice were killed after imaging.
  
  
  RESULTS
  Handheld confocal imaging produced exquisite images, well-correlated with corresponding histologic sections, of cellular shape and tissue architecture in murine brain infiltrated by glial neoplasm. Reproducible patterns of cortical vasculature, as well as normal gray and white matter, were identified. Imaging effectively distinguished between tumor and nontumor tissue, including infiltrative tumor margins. Margins were easily identified by observers without prior neuropathology training after minimum experience with the technology.
  
  
  CONCLUSIONS
  Miniaturized handheld confocal imaging may assist neurosurgeons in detecting infiltrative brain tumor margins during surgery. It may help to avoid sampling error during biopsy of heterogeneous glial neoplasms, with the potential to supplement conventional intraoperative frozen section pathology. Clinical trials are warranted on the basis of these promising initial results.
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.
authors.forename: Tejas
authors.initials: T
authors.lastname: Sankar
authors.forename: Peter M
authors.initials: PM
authors.lastname: Delaney
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ryan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eschbacher
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdelwahab
authors.forename: Peter
authors.initials: P
authors.lastname: Nakaji
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Coons
authors.forename: Adrienne C
authors.initials: AC
authors.lastname: Scheck
authors.forename: Kris A
authors.initials: KA
authors.lastname: Smith
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spetzler
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000601:surgery*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006804:Ergonomics; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000601:surgery*; D006225:Hand; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods*; D009493:Neurosurgery / Q000379:methods*; D055100:Optical Fibers