Acoustic Radiation Force Enhances Ultrasound Contrast Agent Retention to P-selectin In Vivo

摘要

Recent studies have shown that targeted ultrasoundcontrast agents known as microbubbles (MB) can achieve specific adhesion to intravascular pathology. This may enable noninvasive diagnosis of disease at the molecular level using contrastenhanced ultrasound (CEU). However, several investigations have suggested that the ability of injected contrast agents to contact the blood vessel surface, where the molecular markers of disease are located, may to be weak, especially in large or high-flow vessels. This deficiency may limit the usefulness of targeted CEU using these agents. It has been hypothesized that the efficacy of this technique may be improved by increasing the number of circulating MB that contact and adhere to the intended endothelial target site. Low-intensity acoustic radiation has been used to cause the directional migration of targeted MB toward the vessel wall in several in vitro systems. In the current study we present evidence that this technique enhances adhesion of MB targeted to the pro-inflammatory endothelial protein Pselectin in vivo. We assessed the retention of MB bearing the anti-P-selectin antibody Rb40.34 in mouse models of inflammation of the cremaster microcirculation and the femoral vessels. Low-intensity acoustic force was applied for several minutes immediately after MB injection, and MB retention was assessed using intravital microscopy in 10-20 microscopic fields of view. Targeted MB exhibited a 5-fold greater retention following application of acoustic radiation in the cremaster microcirculation, a 2.5-fold increase in the femoral vein, and a 20-fold increase in the femoral artery. These results suggest that low-intensity radiation force is a viable mechanism for enhancing MB retention for imaging inflammation.