title: Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities.
abstract: BACKGROUND
  The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed.
  
  
  METHODS
  A COMPREHENSIVE LITERATURE SEARCH WAS PERFORMED UTILIZING PUBMED AND KEY WORDS: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics.
  
  
  RESULTS
  Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications.
  
  
  CONCLUSIONS
  In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery.
authors.affiliation: Neurosurgery Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Aqib H
authors.initials: AH
authors.lastname: Zehri
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Ramey
authors.affiliation: Neurosurgery Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA ; School of Life Sciences, Arizona State University, Tempe, Arizona, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Georges
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mooney
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA ; Division of Neurosurgery, Department of Surgery, The University of Arizona, Tucson, AZ, Arizona, USA.
authors.forename: Nikolay L
authors.initials: NL
authors.lastname: Martirosyan
authors.affiliation: Neurosurgery Research Laboratory, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Preul
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Nakaji
keywords: Brain neoplasm; confocal endomicroscopy; fluorescent dyes; intraoperative imaging; neuronavigation; optical imaging