Ultrasound molecular imaging of endothelial cell activation and damage in atherosclerosis

Atherosclerosis is a gradual process that evolves over decades with variable plaque morphologies that can lead to atherothrombotic complications such as stroke and acute coronary syndromes. The ability to image the structural, cellular, or biochemical signatures of high-risk plaque phenotype has been a major goal for essentially all forms of clinical and preclinical imaging. These efforts have been based on the need to better understand pathobiology, the need to have a biologic readout for the testing of efficacy for new treatment strategies, and for the clinical purposes of potentially selecting patients for more aggressive forms of anti-atherosclerotic treatments that are in development stage. Ultrasoundbased evaluation of plaque severity and plaque composition is already an integral part of the practice of cardiovascular medicine in the form of extracorporeal and intravascular imaging. New ultrasound-based techniques are being developed that may provide incremental information to structure alone. Some of these techniques are based on the ability to detect vascular inflammation by either regional abnormalities in the mechanical properties of the vessel wall or presence of plaque neovessels using contrast ultrasound imaging. Molecular imaging with acoustically active agents targeted to endothelial cell adhesion molecules, platelets, and microthrombosis has also been used to evaluate high-risk phenotype. Although clinical translation is a distant goal, the impact of ultrasound-based molecular imaging is already being felt through its application to better define pathophysiology and evaluate new therapies in atherosclerotic disease.