In vivo droplet vaporization for occlusion therapy and phase aberration correction

Abstract

The objective was to determine whether a transpulmonary droplet emulsion (90%, <6 m diameter) could be used to form large gas bubbles (>30 m) temporarily in vivo. Such bubbles could occlude a targeted capillary bed when used in a large number density. Alternatively, for a very sparse population of droplets, the resulting gas bubbles could serve as point beacons for phase aberration corrections in ultrasonic imaging. Gas bubbles can be made in vivo by acoustic droplet vaporization (ADV) of injected, superheated, dodecafluoropentane droplets. Droplets vaporize in an acoustic field whose peak rarefactional pressure exceeds a well-defined threshold [1], [2]. In this new work, it has been found that intraarterial and intravenous injections can be used to introduce the emulsion into the blood stream for subsequent ADV (Band M-mode on a clinical scanner) in situ.Intravenous administration results in a lower gas bubble yield, possibly because of filtering in the lung, dilution in the blood volume, or other circulatory effects. Results show that for occlusion purposes, a reduction in regional blood flow of 34% can be achieved. Individual point beacons with a +24 dB backscatter amplitude relative to white matter were created by intravenous injection and ADV.

Towards Aberration Correction of Transcranial Ultrasound Using Acoustic Droplet Vaporization

“…No effort was placed in determining the minimum pulse-lengths or pressure amplitude needed to cause ADV. It has been seen that there are multiple regimes for inducing ADV when using different values for variables such as frequency, pulse-length, pressure amplitude, and UCA (Kripfgans et al, 2002;Giesecke and Hynynen, 2003;Lo et al, 2007). Further study of these mechanisms and their corresponding thresholds should be performed to see which ones will be most amenable to achieving transcranial ADV with conditions that would be acceptable for in vivo studies.…”

“…While there may be some circumstances where transient point-targets are suitable and/or desirable, stable bubbles could be advantageous in several ways. In particular, stable bubbles should allow for more robust and time-consuming point-target aberration correction algorithms, and they may also be used for subsequent therapy when produced in appropriate concentrations (Kripfgans et al, 2002;Psychoudakis et al, 2004).…”

“…This will require a trade-off between minimizing aberration and minimizing the vaporization threshold and spot size. It has also been found that acoustic pressure amplitudes from some diagnostic ultrasound systems are sufficient to vaporize an ADV bubble (Kripfgans et al, 2002).…”

“…Preliminary animal studies have shown the in vivo applicability of ADV (Kripfgans et al, 2002(Kripfgans et al, , 2005. Specifically, DDFP droplets have been vaporized at particular locations in the canine brain after a standard bilateral craniotomy.…”

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.…”