Application of acoustic droplet vaporization in ultrasound therapy.

Microbubbles have been used widely both in the ultrasonic diagnosis to enhance the contrast of vasculature and in ultrasound therapy to increase the bioeffects induced by bubble cavitation. However, due to their large size, the lifetime of microbubbles in the circulation system is on the order of minutes, and they cannot penetrate through the endothelial gap to enter the tumor. In an acoustic field, liquefied gas nanoparticles may be able to change the state and become the gas form in a few cycles of exposure without significant heating effects. Such a phenomenon is called as acoustic droplet vaporization (ADV). This review is intended to introduce the emerging application of ADV. The physics and the theoretical model behind it are introduced for further understanding of the mechanisms. Current manufacturing approaches are provided, and their differences are compared. Based on the characteristic of phase shift, a variety of therapeutic applications have been carried out both in vitro and in vivo. The latest progress and interesting results of vessel occlusion, thermal ablation using high-intensity focused ultrasound (HIFU), localized drug delivery to the tumor and cerebral tissue through the blood-brain barrier, localized tissue erosion by histotripsy are summarized. ADV may be able to overcome some limitations of microbubble-mediated ultrasound therapy and provide a novel drug and molecular targeting carrier. More investigation will help progress this technology forward for clinical translation.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review and introduce the emerging applications, underlying physics, manufacturing approaches, and therapeutic uses of acoustic droplet vaporization (ADV) to inform its clinical translation.

Cargo name and characteristics Liquefied gas nanoparticles (phase-change nanoparticles/droplets that undergo acoustic droplet vaporization under ultrasound; nanoparticle-based carriers for localized drug/molecular targeting and therapeutic effects)

Outcomes and Safety

Summary of Outcomes Acoustic droplet vaporization (ADV) produces controlled phase-change bubbles that enable vessel occlusion, enhance HIFU thermal ablation, enable localized drug delivery including across the BBB, and cause localized tissue erosion (histotripsy) while prolonging circulation and favoring stable over inertial cavitation; reported effective ultrasound conditions include bursts from commercial echosonographic systems, high‑intensity focused ultrasound (HIFU) pulses, and generally higher acoustic pressures (with outcomes dependent on frequency, amplitude and pulse length) required to vaporize submicron droplets.

Duration of biological effect 12–24 h

Safety-related matter Authors report that ADV generally has acceptable toxicity comparable to conventional perfluorocarbon contrast agents, with injections of fluorocarbon emulsions causing short- and long-term effects that spontaneously resolve within 12–24 h; an adverse effect of "pulmonary hyperinflation" was observed in some animals but is considered less likely in humans, and toxicity of stabilizing surfactants must be considered. Compared with microbubble cavitation, vaporized droplets show more stable and less inertial cavitation suggesting minimal surrounding tissue damage for localized delivery, though safety parameters and acoustic thresholds require further investigation.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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