Authors: Evgenii Belykh; Xiaochun Zhao, MD; Claudio Cavallo, MD; Arpan Patel, MD; Leandro Borba Moreira; Sirin Gandhi, MD; Michael Lawton; Peter Nakaji; Mark Preul (Irkutsk, Russian Federation)


Intraoperative techniques for blood flow assessment are essential for cerebrovascular surgery. Fluorescence-based angiography using indocyanine green (ICG) or fluorescein sodium (FNa) and operating microscope with special optical filters has become a useful intraoperative adjunct. These techniques are limited in need for resolution and ability to visualize flow changes over a more prolonged time as relevant information is generally obtained intraoperatively during the first 20 seconds after fluorescent contrast injection. We report the first study to assess intraoperative hand-held confocal laser endomicroscopy (CLE) for cerebral vascular imaging with FNa in a large animal model and experimental brain tumors.


After craniotomy and IV/IA FNa administration we imaged blood flow in cortical vessels of 5 swine and murine experimental invasive gliomas using CLE. Wide field operating microscope angiography with ICG and FNa were performed for comparison. Blood flow was assessed in cortical arteries, veins and brain capillaries in normal conditions, after vessel occlusion, trauma and blood flow arrest and in tumor-associated blood vessels and surrounding brain. Confocal images were acquired in video-like format and as 3D volumetric imaging.


We observed erythrocyte movements in cortical vessels smaller than 1mm diameter. Vessel tortuosity and flow pattern differentiated arteries and veins. Visualization of Normal: vessel thrombosis, flow arrest and redistribution, speed changes, agglutination, cells rolling; Tumor: microvasculature cell invasion, sinusoids, shape irregularity, fluorophore leakage, margin-region transitions. CLE provided longer flow visualization (40min after 2mg/ml FNa) compared to ~6 min with operating microscope. ICG co-administration did not interfere with CLE quality. FNa reinjection was feasible for continuous flow visualization over 5hrs surgery.


CLE imaging allows exquisite assessment of cerebral and tumor vasculature and blood flow alterations with subcellular resolution on-the-fly intraoperatively. CLE offers extended imaging time compared with fluorescence angiography with operating microscope and shows unique precise details of intravascular cell movements.