Current and Emerging Preclinical Approaches for Imaging-Based Characterization of Atherosclerosis

Atherosclerotic plaques can remain quiescent for years, but become life threatening upon rupture or disruption, initiating clot formation in the vessel lumen and causing acute myocardial infarction and ischemic stroke. Whether and how a plaque ruptures is determined by its macroscopic structure and microscopic composition. Rupture-prone plaques usually consist of a thin fibrous cap with few smooth muscle cells, a large lipid core, a dense infiltrate of inflammatory cells, and neovessels. Such lesions, termed high-risk plaques, can remain asymptomatic until the thrombotic event. Various imaging technologies currently allow visualization of morphological and biological characteristics of high-risk atherosclerotic plaques. Conventional protocols are often complex and lack specificity for high-risk plaque. Conversely, new imaging approaches are emerging which may overcome these limitations. Validation of these novel imaging techniques in preclinical models of atherosclerosis is essential for effective translational to clinical practice. Imaging the vessel wall, as well as its biological milieu in small animal models, is challenging because the vessel wall is a small structure that undergoes continuous movements imposed by the cardiac cycle as it is adjacent to circulating blood. The focus of this paper is to provide a state-of-the-art review on techniques currently available for preclinical imaging of atherosclerosis in small animal models and to discuss the advantages and limitations of each approach.