Detection of inflamed plaques with contrast ultrasound

Inflammatory cell infiltration is an important factor in the progression and instability of atherosclerotic plaques. There has been great interest in the development of noninvasive methods that can assess these inflammatory processes to detect vulnerable plaques or patients, and to assess novel therapies. This review focuses on some recent advances in contrast-enhanced ultrasound (CEU), which can potentially be used for imaging plaque inflammation. These methods rely on ultrasound detection of microbubble contrast agents that are targeted to inflamed tissue. For this purpose, novel microbubbles have been formulated that are targeted either to activated leukocytes adherent to inflamed endothelium, or to endothelial cell adhesion molecules (p-selectin, intercellular adhesion molecule-1, αvβ3) expressed on the plaque surface or within plaque neovessels. Microbubble targeting has been achieved by modifications of shell components or conjugation of specific ligands to the shell surface. Although application of targeted CEU for imaging inflamed plaques is at the early stages of development, it is potentially easily translatable to routine clinical practice because the technique is relatively inexpensive, portable, and uses technology that already is used widely to evaluate vascular disease.