Mutual Attraction of Oscillating Microbubbles

Abstract

The driving of contrast microbubbles towards a boundary by means of primary radiation 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. The thick-shelled contrast agent M1639, inserted through a cellulose capillary, was subjected to 3 MHz, high-MI pulsed ultrasound from a commercial ultrasound machine, and synchronously captured through a high numerical aperture microscope. The agent showed the ultrasound-induced formation of bubble clusters, and the translation thereof towards the capillary boundary. Hence, forced translation and clustering of thick-shelled contrast microbubbles is feasible. 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, approach velocities of encapsulated bubbles may not be comparable to those of free gas bubbles.