Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases

Abstract

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging–matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3–73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas.</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.</jats:p></jats:sec>

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

“…Sixty-four studies describe the clinical use of fluorescent agents [1, 3, 5, 6, 9, 11, 13–16, 22–26, 28–31, 33–35, 37, 38, 40–42, 44, 49, 52–54, 58, 64–66, 69, 71, 74, 75, 78, 80–82, 84–87, 89, 92, 94, 97–101, 105–107, 109, 110, 113, 115, 118]. Three ways of labeling tumor cells were identified in the literature: (1) passive, (2) metabolic, and (3) molecular labeling.…”

“…Eleven papers described the use of fluorescein as a fluorescent agent in glioma surgery [1, 11, 23, 38, 52, 54, 64, 65, 71, 86, 92]. All were observational studies including patients with HGG.…”

“…All were observational studies including patients with HGG. Only three studies included patients with LGG [11, 64, 86]. Fluorescein is a passive targeting agent commonly used for ophthalmic examinations of the retina [67].…”

“…It is excited at a wavelength of 460–500 nm and has an emission spectral range of 540–690 nm. As this is within the spectrum of visible light, fluorescein is used with [1, 23, 27, 38, 54, 71, 86, 120] or without a filter on the surgical microscope [11, 52, 64, 65, 92]. …”

Real‐Time Imaging of Brain Tumor for Image‐Guided Surgery

“…[66] Fluorescent and nonfluorescent areas correlated with tumor–normal brain distinction was confirmed histologically with the sensitivity of 82–94% and the specificity of 90–95%. [67–69] …”