Acoustic droplet vaporization is initiated by superharmonic focusing

Abstract

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.

Monodisperse bubbles and droplets for medical applications

“…7). This is an entirely different mechanism from the recently proposed focusing effect 175 . Good agreement was found between the modeled size-dependent pressure amplification within the droplet and the measured size dependent vaporization probability.…”

“…From the pressure profile of the resonant droplet it can also be observed that the amplitude of the pressure at the droplet center exceeds the incident pressure by a factor 2.2. The higher pressure amplification in the center of the droplet results in the largest probability of finding nucleation sites in the center of the droplet, in contrast to the previously developed superharmonic focusing theory 175 .…”

“…Several groups have reported the decrease in the acoustic pressure threshold for increasing driving frequencies 161,171,173,174 . Recently, Shpak et al 175 have revealed that droplet vaporization is initiated by focusing of the nonlinear acoustic wave by the spherical droplet due to a mismatch in acoustic impedance between the PFC droplet and the surrounding water. The multiple superharmonics generated during the non-linear propagation of the acoustic wave reach wavelengths on the order of the size of the droplet allowing for a superharmonic focusing effect to occur.…”

“…Moreover, the vaporization of microdroplets is of interest for embolotherapy applications 171,190 . Recently, Shpak et al 175 showed that the vaporization of droplets with ultrasound frequencies in the MHz range is induced by the focusing of superharmonic waves, generated by nonlinear propagation of the ultrasound, with wavelengths of the order of the droplet size. The peak negative pressure in the focal region is droplet size and frequency dependent, in other words the vaporization efficiency is governed by a strong coupling between droplet size and the pressure and frequency of the ultrasound wave.…”

“…Het resonante verdampingsmechanisme is nieuw en verschilt van het eerder gevonden verdampingsmechanisme waarbij geluidsgolven focusseren in de druppel 175 . We vonden een goede overeenkomst tussen de gemodelleerde en de gemeten druppelgrootte-afhankelijke verdampingsefficiëntie.…”