Use of Acoustically Active Contrast Agents in Imaging of Inflammation and Atherosclerosis
Inflammation plays an important role in the development of atherosclerosis. The endothelium is an active organ that forms a barrier between the circulation and the arterial wall. In response to pro-atherogenic factors, the endothelium is induced to become an adhesive and pro-thrombotic surface. A range of molecular markers associated with early and late changes in atherogenesis have been identified in the endothelium. Those pathological changes in the endothelium are potential targets for early detection of atherosclerosis and may precede advanced changes that can be detected by conventional imaging modalities, such as coronary angiography. Acoustically active contrast agents have been widely used for clinical applications such as enhancing cardiac chamber definition and measuring myocardial perfusion in diagnostic ultrasound imaging. In the context of molecular imaging, those agents are pure intravascular tracers and are ideally suited for interrogating the expression of molecular markers on the endothelium. Studies have demonstrated how microbubbles can detect inflammation by means of the interactions between their lipid shell components and leukocytes that co-localize on the surface of inflamed endothelium. More sophisticated acoustically active targeting agents, however, involve the incorporation of high-affinity peptides or antibodies into their lipid shell that highlight inflammatory markers, thrombosis, and neovascularization in the arterial wall in atherosclerotic animal models. Before those agents can be widely used in clinical practice, they will require further refinements to reduce immunogenicity of targeting ligands, minimize toxicity of lipid shell components, and improve acoustic stability after intravenous administration. The most challenging aspect of this research is, however, the identification of clinically relevant markers that can accurately predict the presence and progression of atherosclerosis.
KeywordsContrast Agent Intravascular Ultrasound Ultrasound Contrast Agent Acoustic Reflectivity Perfluorocarbon Emulsion
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