Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Abstract

Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and 5 were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5 MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 minutes per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intra renal artery or IV administered droplets, with a tissue path up to 5.5 cm.

Phase-transition Perfluorocarbon Nanoparticles for Ultrasound Molecular Imaging and Therapy

“…From then award, ADV has been profoundly investigated in the group works of Michigan University with albumin coated perfluoropentane (PFP) nanoparticles, which illustrated substantially applications PFC nanoparticles with ADV in terms of drug delivery, thrombolysis, and gas embolism, etc. [33][34][35][36][37][38][39][40][41][42][43]. Table 1 lists some parameters of candidate perfluorocarbons.…”

“…Currently, PFC nanoparticles show promise for effectively targeted tissue occlusion [38,134]. In Zhang et al's study, substantial localized tissue occlusion was achieved in canine kidneys by gas bubbles in the renal arteries or segmental arteries, which were generated by phase-transition PFC droplets encapsulated in lipid shells or albumin in the blood [38].…”

“…Currently, PFC nanoparticles show promise for effectively targeted tissue occlusion [38,134]. In Zhang et al's study, substantial localized tissue occlusion was achieved in canine kidneys by gas bubbles in the renal arteries or segmental arteries, which were generated by phase-transition PFC droplets encapsulated in lipid shells or albumin in the blood [38]. Another study by the same group results that 125 μm arterioles (average diameter) and the 4-7 μm capillary beds in Sprague-Dawley rats can be occluded with ultrasonically activated gas bubbles converted by albumin-encapsulated PFC nanoparticles (Samuel et al) [135].…”

High-intensity focused ultrasound-triggered nanoscale bubble-generating liposomes for efficient and safe tumor ablation under photoacoustic imaging monitoring

“…If these huge microbubbles circulate in the blood, there is an increase in the risk of vascular and pulmonary embolism. 25,26 Microbubbles used clinically are no more than 10 µm to avoid the risk of embolism. Due to these issues, the safety of HIFU synergists requires further study.…”

Monodisperse bubbles and droplets for medical applications

“…In addition, vaporized droplets form highly echogenic vapor bubbles resonant to standard diagnostic ultrasound frequencies which allows for monitored drug delivery and tumor imaging. 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.…”