Acoustic Droplet Vaporization: Strategies for Control of Bubble Generation and its Application in Minimally Invasive Surgery.

Abstract

As a minimally invasive alternative to current cancer treatment, the use of encapsulated, superheated liquid perfluorocarbon droplets has been proposed to treat cancer by occlusion therapy. In response to an acoustic field, these droplets, which are small enough to pass through capillaries, vaporize into large gas bubbles that subsequently lodge in the vasculature. This research investigates strategies to reduce the pressures necessary to achieve acoustic droplet vaporization (ADV), what implications they may have on efficiency, and how the resulting location of bubbles may alter the acoustic field.

Two methods to lower the ADV threshold were explored. The first investigated the role of pulse duration on ADV. The second investigated the role of inertial cavitation (IC) external to a droplet by adding ultrasound contrast agent (CA), which has a low IC threshold. At 1.44 MHz, the threshold was found to be 5.5-5.9 MPa peak rarefactional pressure (Pr) for short microsecond pulses and decreased for millisecond pulses to 3.8-4.6 MPa Pr. When CAs were added and long millisecond pulses were used, the ADV threshold decreased to values as low as 0.41 MPa Pr.

With the help of CA, the same amount of power was necessary to achieve ADV through an attenuating tissue mimicking (TM) phantom as it was without attenuation and with only droplets. When comparing ADV pressure thresholds, where in situ pressures were used when a TM phantom was present, rarefactional pressure appeared to be the salient determinant. However, careful consideration must be taken when choosing pulse repetition frequencies and amplitude as inertial collapse of both ADV and IC bubbles appears to affect efficient droplet conversion.

During in vivo application, treatment planning may be important as backscattering properties of microbubbles created by ADV can augment or obstruct the sound field in the affected area. With strategic targeting and subsequent conversion of droplets into microbubbles, constructive interference due to these effects reduces the transmitted pressures required for proximal ADV, and the attenuation from these bubbles can create a protective boundary for distal areas. The potential result can be a confined area for further ADV where lower pressures are required to cause vaporization.