P2A-6 Contrast Microbubble Clustering at High MI

The driving of contrast microbubbles towards a boundary by means of primary radiation (Bjerknes) forces has been of interest for ultrasound-assisted drug delivery. Secondary radiation forces, resulting from oscillating microbubbles under ultrasound insonification, may cause the mutual attraction and subsequent coalescence of contrast microbubbles. This phenomenon has been less studied. Microbubbles with a negligible shell can be forced to translate towards each other at relatively low mechanical indices (MI). Thick-shelled microbubbles would require a higher MI to be moved. However, at high MI, microbubble disruption is expected. We investigated if thick-shelled contrast agent microbubbles can be forced to cluster at high-MI. Two thick-shelled contrast agents, inserted through a cellulose capillary, were subjected to 3 MHz, high-MI pulsed ultrasound from a commercial ultrasound machine, and synchronously captured through a high numerical aperture microscope. The agent Quantisontrade did not translate, but showed a small percentage of disrupted bubbles. The agent M1639 showed the ultrasound-induced formation of bubble clusters, and the translation thereof towards the capillary boundary. It is concluded, that forced translation and clustering of thick-shelled contrast microbubbles is feasible