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.Conclusion: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.

Intraoperative Robotic-Assisted Large-Area High-Speed Microscopic Imaging and Intervention

“…These high resolution microscopy images can be acquired at video rates by relaying light to and from the tissue using fibre-optic imaging bundles and a micro-lens, allowing a compact probe design without complex mechanical components [4]. Preliminary studies have shown potential applications in neurosurgery [5] for optimising resection, in head and neck surgery [6] for early detection and resection of squamous cell carcinomas, in breast surgery [7], [8] for distinguishing neoplastic from non-neoplastic cells, and for diagnostic purposes in gastrointestinal, colorectal, gastric, urinary tract, ovarian and lung cancer [9].…”

Optical technologies for intraoperative neurosurgical guidance

“…27,34,88,91,120,122,123,126,172 Schlosser et al provided the first report on confocal microscopy in neurosurgery. They examined intraoperatively ex vivo samples from 9 patients with GBM immediately following excision and reported the ability of this technology to identify features such as cell density, mitotic figures, necrosis, and microvascular proliferation.…”

The Art of Intraoperative Glioma Identification

“…This is also referred to as optical sectioning and allows visualization of the tumor in one plane. This technology reduces fluorescent light scatter, thus, resulting in higher resolution and contrast images, with in vivo magnification up to 1000× ( 47 ). Intraoperative visualization of brain tumors is greatly enhanced by new technologies of 5-ALA with confocal microscopy that is of importance not only for resection of high-grade gliomas but also for intraoperative visualization of anaplastic foci in a tumor initially suspected of being low grade ( 48 ).…”