Contrast microbubble clustering and coalescence
Résumé
Forced translation of contrast microbubbles has been associated with novel drug delivery methods. Secondary radiation forces, resulting from oscillating microbubbles under ultrasound insonification, may cause the mutual attraction and subsequent coalescence of contrast microbubbles. Microbubbles with a negligible shell can be forced to translate towards each other at moderate acoustic amplitudes. Thick-shelled microbubbles would require a higher acoustic pressure to be moved. However, in this regime, microbubble disruption is expected. We investigated under what conditions contrast agent microbubbles can be forced to cluster and coalesce. Several contrast agents were inserted through a cellulose capillary and subjected to 3 MHz, pulsed ultrasound from a commercial ultrasound machine, and synchronously captured through a high numerical aperture microscope. Moreover, we simulated the microbubble translation behavior. Apart from disruptive effects at high acoustic amplitudes, the agents showed the ultrasound-induced formation of bubble clusters, and the translation thereof towards the capillary boundary. Forced translation and clustering of thick-shelled contrast microbubbles is feasible. Coalescence, however, has only been observed with thin-shelled agents. The phase difference between the excursion of the oscillating bubble and the incident sound field was computed for free and encapsulated bubbles. There is a transition in phase difference for encapsulated bubbles, owing to the friction of the shell. Therefore, the approach velocities of encapsulated bubbles are not comparable to those of free gas bubbles.