Multispectral molecular imaging of capillary endothelium to facilitate preoperative endovascular brain mapping

Abstract

Brain mapping aims to localize neurological function to specific regions of the human brain. Preoperative endovascular brain mapping (PEBM) is a novel approach that allows clear visualization of nonfunctional (silent) brain parenchyma in real time during a resection. It has potential to improve neurosurgical guidance because brain shift does not alter the maps, and the map is visualized directly on the brain in situ rather than on a nearby image. Therefore, the risk of a new neurological deficit should be reduced. The authors report the first PEBM approach that combines selective molecular targeting of brain endothelium with multispectral (optical) imaging in preclinical animal models. Sprague-Dawley rats and New Zealand white rabbits were selectively catheterized, and a fluorescein isothiocyanate–derivatized tomato lectin–based imaging probe was administered into the carotid artery or posterior cerebral artery, measuring < 500 μm in diameter. After binding/uptake of the imaging probe, and removal of unbound probe, a craniotomy was performed to directly visualize the “brain map.” Selective localization of the imaging probe to the right hemisphere in rats or right posterior cerebral artery in rabbits was clearly visualized after craniotomy. Cross-sections of stained capillaries demonstrated that the imaging probe did not cause vascular occlusion. Gross regional selectivity of the imaging probe was documented by multispectral molecular imaging of intact brains, with discrete localization and endothelium-directed targeting validated by histological examination. The authors have demonstrated the first molecular endothelium-targeted approach to PEBM that does not require manipulation of the intact blood-brain barrier or result in vascular occlusion. Furthermore, the presented multispectral molecular imaging technique appears to be a suitable methodology for the generation of region-selective brain maps of vascularized brain parenchyma. Further refinement of the PEBM approach, as well as the development of improved imaging probes, may result in clinical advancement of PEBM where direct visual discrimination of nonfunctional silent brain parenchyma at the time of resection could significantly improve neurosurgical outcomes.