Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy, or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold; its frequency dependence does not comply with homogeneous nucleation theory and localized nucleation spots have been observed. Here we show that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths of the order of the droplet size. These superharmonics strongly contribute to the focusing effect; therefore, the proposed mechanism also explains the observed pressure thresholding effect. Our interpretation is validated with experimental data captured with an ultrahigh-speed camera on the positions of the nucleation spots, where we find excellent agreement with the theoretical prediction. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency. The physical insight allows for the optimization of acoustic droplet vaporization for therapeutic applications, in particular with respect to the acoustic pressures required for activation, thereby minimizing the negative bioeffects associated with the use of high-intensity ultrasound.

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In this paper we study both experimentally and theoretically the dynamics of an ultrasound-driven vapor bubble of perfluoropentane (PFP) inside a droplet of the same liquid, immersed in a water medium superheated with respect to the PFP boiling point. We determine the temporal evolution of the bubble radius with ultra-high speed imaging at 20 million frames per second. In addition, we model the vapor-gas bubble dynamics, based on a Rayleigh-Plesset-type equation, including thermal and gas diffusion inside the liquid. We compare the numerical results with the experimental data and find good agreement. We underline the fundamental role of gas diffusion in order to prevent total recondensation of the bubble at collapse.

Acoustically sensitive emulsions are a promising tool for medical applications such as localized drug delivery. The physical mechanisms underlying the ultrasound-triggered nucleation and subsequent vaporization of these phase-change emulsions are largely unexplored. Here, the acoustic vaporization of individual micron-sized perfluoropentane (PFP) droplets is studied at a nanoseconds timescale. Highly diluted emulsions of PFP-in-water and oil-in-PFP-in-water droplets, ranging from 3.5 to 11 μm in radius, were prepared and the nucleation and growth of the vapor bubbles was imaged at frame rates of up to 20 Mfps. The droplet vaporization dynamics was observed to have three distinct regimes: (1) prior to nucleation, a regime of droplet deformation and oscillatory translations within the surrounding fluid along the propagation direction of the applied ultrasound; (2) a regime characterized by the rapid growth of a vapor bubble enhanced by ultrasound-driven rectified heat transfer; and (3) a final phase characterized by a relatively slow expansion, after ultrasound stops, that is fully dominated by heat transfer. A method to measure the moment of inception of the nucleation event with respect to the phase of the ultrasound wave is proposed. A simple physical model captures quantitatively all of the features of the subsequent vapor bubble growth.

The interaction of droplets and bubbles with ultrasound has been studied extensively in the last 25 years. Microbubbles are broadly used in diagnostic and therapeutic medical applications, for instance, as ultrasound contrast agents. They have a similar size as red blood cells, and thus are able to circulate within blood vessels. Perfluorocarbon liquid droplets can be a potential new generation of microbubble agents as ultrasound can trigger their conversion into gas bubbles. Prior to activation, they are at least five times smaller in diameter than the resulting bubbles. Together with the violent nature of the phase-transition, the droplets can be used for local drug delivery, embolotherapy, HIFU enhancement and tumor imaging. Here we explain the basics of bubble dynamics, described by the Rayleigh-Plesset equation, bubble resonance frequency, damping and quality factor. We show the elegant calculation of the above characteristics for the case of small amplitude oscillations by linearizing the equations. The effect and importance of a bubble coating and effective surface tension are also discussed. We give the main characteristics of the power spectrum of bubble oscillations. Preceding bubble dynamics, ultrasound propagation is introduced. We explain the speed of sound, nonlinearity and attenuation terms. We examine bubble ultrasound scattering and how it depends on the wave-shape of the incident wave. Finally, we introduce droplet interaction with ultrasound. We elucidate the ultrasound-focusing concept within a droplets sphere, droplet shaking due to media compressibility and droplet phase-conversion dynamics.