BACKGROUND: Intravascular optical coherence tomography (OCT) is a recently developed optical imaging technique that provides high-resolution cross-sectional in situ images from intact tissue based on tissue reflectance of near-infrared or infrared light. OBJECTIVE: To report on the feasibility of neuroendovascular OCT imaging and compare the neuroendovascular OCT findings with histology in nondiseased vessels in an animal, cadaveric, and clinical study. METHODS: Catheter-based in vivo endovascular OCT imaging was performed in the common carotid arteries of 2 pigs and in the intracranial carotid arteries of 3 patients. The endovascular OCT device was delivered to the desired location via groin access and using standard endovascular procedures. Images were obtained via rotational and translational scanning using external motors. In vivo findings were reproduced using ex vivo OCT imaging in corresponding animal and human (cadaveric) harvested tissue segments. These segments underwent histological examination for comparison. RESULTS: The structural compositions of the OCT-imaged segments of the common carotid arteries in pigs as well as the petrous and cavernous intracranial carotid arteries in patients were visualized at high resolution (8 μm). The in vivo images were identical to those obtained ex vivo, demonstrating the imaging capabilities of the endovascular OCT device. The OCT images correlated well with the images obtained after histological sectioning and visualized in vivo the laminar vascular structure. CONCLUSION: Neuroendovascular OCT imaging is feasible for clinical use and can detect with high resolution the structure of arterial segments. Understanding OCT imaging in nondiseased arteries is important in establishing baseline findings necessary for interpreting pathological processes. This allows neuroendovascular optical biopsies of vascular tissue to be obtained without the need for excision and processing. Copyright © 2011 by the Congress of Neurological Surgeons.