Enhanced targeting of ultrasound contrast agents using acoustic radiation force

Contrast-enhanced ultrasound has shown significant promise as a molecular imaging modality. However, one potential drawback is the difficulty that ultrasound contrast agents (UCA) may have in achieving adhesion to target molecules on the vascular endothelium. Microbubble UCA exhibit a lateral migration toward the vessel axis in laminar flow, preventing UCA contact with the endothelium. In the current study, we have investigated low-amplitude acoustic radiation as a mechanism to move circulating UCA toward targeted endothelium. Intravital microscopy was used to assess the retention of microbubble UCA targeted to P-selectin in the mouse cremaster microcirculation and femoral vessels. Acoustic treatment enhanced UCA retention to P-selectin four-fold in cremaster venules and in the femoral vein and 20-fold in the femoral artery. These results suggest acoustic treatment as a mechanism for enabling ultrasound-based molecular imaging in blood vessels with hemodynamic and anatomical conditions otherwise adversarial for UCA retention.