With a lipid shell containing biotin, micron-sized bubbles bound to avidin on a porous and flexible cellulose boundary were insonified by ultrasound. The oscillation of these targeted microbubbles was observed by high-speed photography and compared to the oscillation of free-floating microbubbles. Adherent microbubbles were observed to oscillate asymmetrically in the plane normal to the boundary, and nearly symmetrically in the plane parallel to the boundary, with a significantly smaller maximum expansion in each dimension for bound than free bubbles. With sufficient transmitted pressure, a jet was produced traveling toward the boundary.There is a great interest in developing molecularly targeted ultrasound contrast agents due to the potential medical applications. [1][2][3][4] The agents are gas bubbles with a diameter on the order of a few microns and a shell of albumin, lipid, or polymer. After intravenous injection, peptides or antibodies attached to the shells link the agents to a receptor on endothelial cells. Because of their high echogencity, these targeted agents can be detected by an ultrasound system with high sensitivity, and therefore can provide important information such as the spatial distribution and extent of tumor angiogenesis, 5,6 inflammatory response, 7,8 or thrombus. 9 Current contrast imaging schemes are not yet optimized for imaging these targeted agents because the microbubbles retained in tissue are limited in number, 5,9 and the signal from adherent microbubbles can be masked by the signal from freely circulating microbubbles. Strategies for imaging these agents currently require waiting for clearance of free-floating microbubbles or employing image averaging and subtraction techniques. Neither of these techniques is optimal since they require either a time delay, or multiple frames, which impede real-time imaging. Hence, there is a need for the development of a new selective and sensitive method for detecting adherent microbubbles, which will depend on our understanding of the acoustic behavior of a targeted microbubble after it binds to a targeting site.Mathematical simulations have been developed for modeling microbubble radial oscillation with different assumptions and simplifications. [10][11][12] High-speed micrography has been used to study microbubble radial oscillation, 13 translation, 14 and fragmentation. 15 In these studies, a microbubble is assumed to remain spherical and in an infinite medium. Asymmetrical oscillation of a cavitation bubble and formation of a jet have been studied both theoretically and experimentally by a number of research groups, [16][17][18] although previous experimental studies have involved unencapsulated bubbles of a diameter larger than micron-sized contrast agents, and have not used ultrasound as an excitation source. The behavior of a targeted microbubble after it binds to a vessel wall and is insonified by an ultrasound pulse has not been reported previously.
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