Imaging targeted microbubble interactions with microvessels

High-speed imaging was used to directly observe the dynamics of targeted microbubbles in microvessels of ex vivo rat mesentery. Targeted microbubbles were prepared by attaching biotinylated CD31 antibody to microbubbles that were coated by straptavidin. Specific microbubbles were identified to be adherent to the vessel wall. An ultrasound pulse of about 2 μs long with peak negative pressure 0.8 MPa or 1.5 MPa interrogated the tissue sample as high-speed photomicrographic images were acquired with 50-ns shutter speeds. Asymmetrical oscillation of adherent microbubbles was observed. At 0.8 MPa, the microbubble remained attached to the vessel wall after exposure of a single ultrasound pulse. However, at 1.5 MPa, microbubble oscillation induced obvious vessel wall distention and invagination, which was accompanied by microbubble detachment and translation away from the vessel wall. The formation of liquid jets was also observed at 1.5 MPa. The adherence of targeted microbubbles to the vessel wall resulted in relatively strong interactions with the vessel walls at the higher ultrasound pressure level. Lower pressure levels are needed to prolong the attachment of the microbubbles.