Contrast-enhanced ultrasound (CEU) relies on the acoustic detection of microbubble or gas-containing nano-scale contrast agents. It is possible to target ultrasound microbubble contrast agents to disease-related cellular and molecular processes that are amenable to pure-intravascular tracers. Targeting relies on conjugating specific ligands to the surface of the microbubbles. This talk will focus on some of the recent advances in molecular imaging with targeted ultrasound contrast agents in angiogenesis and how they can be paired with perfusion and vascular anatomic information available on CEU.
A popular strategy for molecular imaging of adaptive or pathologic angiogenesis has been to target endothelial integrins that participate in vasculogenesis or remodeling. Molecular imaging probes have been targeted to matrix-binding integrins that signal endothelial cell migration, proliferation and survival such as av- and a5-integrins. These agents have been used to examine temporal development of tumor angiogenesis, and endogenous and therapeutic angiogenesis in models of chronic limb ischemia. CEU molecular imaging has also been able to detect key growth factor receptors, such as VEGFR-2, that play a key role in tumor and ischemia-mediated vascular remodeling. The immune response plays a critical role in angiogenesis and arteriogenesis, in part by providing a source for pro-angiogenic growth factors, cytokines, and proteases. Targeted contrast ultrasound imaging of monocyte recruitment and endothelial cell adhesion molecule expression has recently been shown to herald vasculogenesis and vascular remodeling in limb ischemia prior to any significant flow recovery. This strategy also has been used to detect immune response dysfunction associated with impaired arteriogenesis, such as in diabetes mellitus.