Ex Vivo Fluorescein-Assisted Confocal Laser Endomicroscopy (CONVIVO® System) in Patients With Glioblastoma: Results From a Prospective Study

Background: Confocal laser endomicroscopy (CLE) allowing intraoperative near real-time high-resolution cellular visualization is a promising method in neurosurgery. We prospectively tested the accuracy of a new-designed miniatured CLE (CONVIVO (R) system) in giving an intraoperative first-diagnosis during glioblastoma removal. Methods: Between January and May 2018, 15 patients with newly diagnosed glioblastoma underwent fluorescein-guided surgery. Two biopsies from both tumor central core and margins were harvested, dividing each sample into two specimens. Biopsies were firstly intraoperatively ex vivo analyzed by CLE, subsequently processed for frozen and permanent fixation, respectively. Then, a blind comparison was conducted between CLE and standard permanent section analyses, checking for CLE ability to provide diagnosis and categorize morphological patterns intraoperatively. Results: Blindly comparing CONVIVO (R) and frozen sections images we obtained a high rate of concordance in both providing a correct diagnosis and categorizing patterns at tumor central core (80 and 93.3%, respectively) and at tumor margins (80% for both objectives). Comparing CONVIVO (R) and permanent sections, concordance resulted similar at central core (total/partial concordance in 80 and 86.7% for diagnosis and morphological categorization, respectively) and lower at tumor margins (66.6% for both categories). Time from fluorescein injection and time from biopsy sampling to CONVIVO (R) scanning was 134 +/- 31 min (122-214 min) and 9.23 min (1-17min), respectively. Mean time needed for CONVIVO (R) images interpretation was 5.74 min (1-7 min). Conclusions: The high rate of diagnostic/morphological consistency found between CONVIVO (R) and frozen section analyses suggests the possibility to use CLE as a complementary tool for intraoperative diagnosis of ex vivo tissue specimens during glioblastoma surgery.