Scintillating Balloon-Enabled Fiber-Optic System for Radionuclide Imaging of Atherosclerotic Plaques

According to the National Center for Health Statistics 2011 report, coronary artery disease (CAD) remains the leading cause of mortality in the United States in men and women of every major ethnic group. CAD claims more lives each year than the next 4 leading causes of death combined—cancer, chronic lower respiratory diseases, accidents, and diabetes mellitus (1). Disappointingly, CAD has recently become the world’s leading killer, overtaking even infectious diseases in the developing world. Over the last several decades, basic cardiovascular research has significantly enhanced our understanding of pathobiologic processes leading to the formation, progression, and complications of atherosclerotic plaques (2). By harnessing these advances in cardiovascular biology, imaging has advanced beyond its traditional anatomic domains to a tool that permits probing of particular molecular structures to image cellular behavior and metabolic pathways involved in atherosclerosis (2). However, the current clinical paradigm for detecting CAD is angiography, which evaluates only the luminal encroachment of the disease, without providing information about plaque extent and content (3). Also, it has been shown that most plaques that cause acute coronary events are not hemodynamically significant (4). Although a wide range of molecular imaging modalities has been developed for detection and characterization of atherosclerosis in large vessels, detecting high-risk (i.e., vulnerable) plaques in the small, mobile coronary arteries remains a challenge (5–9). Macrophage infiltration in atherosclerotic plaques plays an important role in the progression of atherosclerosis (10). Macrophage-rich inflammation is particularly intense in the high-risk plaques associated with acute coronary events and symptomatic carotid vascular disease (11–14). As a result, macrophages have become widely recognized as a key target for atherosclerosis imaging (15). Several studies have shown that 18F-FDG can be a marker of metabolically active high-risk plaques because of its uptake by inflammatory macrophages in the carotids and aorta (16–18). 18F-FDG PET imaging is based on the higher metabolic glucose demand of macrophages than their surrounding cells in the plaque; upregulated hexokinase increases radiolabeled glucose accumulation through glucose transporters (19). However, PET 18F-FDG detection in coronary plaque is still challenging because of the small size of such plaques, signal blurring due to motion, and obscuring 18F-FDG uptake by adjacent myocardium (20). Therefore, the advent of an intravascular molecular imaging approach has the potential to overcome these limitations by minimizing the distance and maximizing the sensitivity to coronary plaque signal. Previously, we demonstrated the feasibility of a novel dual-modality fiber-optic system with an off-the-shelf scintillating screen (not attached to the system) (21) for plaque 18F-FDG detection. In this current study, we have fabricated and integrated a novel scintillating balloon for our fiber-optic imaging system to detect 18F-FDG–enriched atherosclerotic plaques, which may have the ability to image a 360° degree view of an artery. Therefore, the aims of this study were to develop this fiber-optic imaging system with a scintillating balloon to detect 18F-FDG glucose probe, characterize the system for spatial resolution from multiple scintillating materials, and validate the system on ex vivo macrophage-rich murine plaques with confirmatory external optical imaging and autoradiography.