Dissolved Oxygen Scavenging by Acoustic Droplet Vaporization using Intravascular Ultrasound

Abstract

Modification of dissolved gas content by acoustic droplet vaporization (ADV) has been proposed for several therapeutic applications. Reducing dissolved oxygen (DO) during reperfusion of ischemic tissue during coronary interventions could inhibit reactive oxygen species production and rescue myocardium. The objective of this study was to determine whether intravascular ultrasound (IVUS) can trigger ADV and reduce DO. Perfluoropentane emulsions were created using high-speed shaking and microfluidic manufacturing. High-speed shaking resulted in a polydisperse droplet distribution ranging from less than 1 micron to greater than 16 microns in diameter. Microfluidic manufacturing produced a narrower size range of droplets with diameters between 8.0 microns and 9.6 microns. The DO content of the fluids was measured before and after ADV triggered by IVUS exposure. Duplex B-mode and passive cavitation imaging was performed to assess nucleation of ADV. An increase in echogenicity indicative of ADV was observed after exposure with a clinical IVUS system. In a flow phantom, a 20% decrease in DO was measured distal to the IVUS transducer when droplets, formed via high-speed shaking, were infused. In a static fluid system, the DO content was reduced by 11% when droplets manufactured with a microfluidic chip were exposed to IVUS. These results demonstrate that a reduction of DO by ADV is feasible using a clinical IVUS system. Future studies will assess the potential therapeutic efficacy of IVUS-nucleated ADV and methods to increase the magnitude of DO scavenging.

Keywords: acoustic droplet vaporization; dissolved gas; intravascular ultrasound; microfluidics; oxygen; phase-shift emulsion.

Fig. 1

Schematic of the flow phantom used to assess the ability of an intravascular ultrasound device operating at 40 MHz to nucleate acoustic droplet vaporization and dissolved gas scavenging.

Fig. 2

Normalized (A) number-weighted and (B) volume-weighted size distribution of the droplets manufactured via high speed shaking (black), high-speed shaking with size-isolation via centrifugation (blue), and microfluidic manufacturing (green).

Fig. 3

Duplex B-mode and passive cavitation image of the flow phantom tube with the IVUS catheter inserted. (A) Distal to the IVUS catheter is relatively hypoechoic without IVUS exposure. (B) With IVUS exposure, the lateral location of the element can be identified from the passive cavitation image. Hyperechoic ADV microbubbles are observed distally.

Fig. 4

The average DO content measured by the proximal (light blue and dark blue) DO sensor and the distal (red and orange) DO sensor with and without IVUS exposure. A decrease in DO is measured only distal to the IVUS transducer when droplets are present. Error bars represent the standard deviation of the measurements.