Assessing the oxygen scavenging capacity and myocardial gas embolization risk of ultrasonically activated phase shift perfluorobutane droplets

Abstract

This study investigated oxygen scavenging efficiency and the risk of embolization of the cardiac vasculature using ultrasound-triggered phase-shift perfluorobutane (PFB) droplets in vitro and ex vivo. The emulsion comprised lipid-shelled perfluorobutane core droplets with a modal diameter of 0.98 ± 0.03 µm. The droplets were prepared using a high-pressure microfluidizer. The embolization risk was assessed using a modified ex vivo rat Langendorff preparation to accommodate an EkoSonic™ Endovascular Device. The EkoSonic™ Device was composed of an infusion catheter and an ultrasonic core to generate ultrasound at 2.35 MHz and nucleate acoustic droplet vaporization of the droplets. The oxygen scavenging efficiency was studied in isolated beating heart and an in vitro flow phantom setup with target concentrations ranging from 0.05 × 10−4 to 5.0 × 10−4 mL/mL. Gas embolization from the acoustic droplet vaporization-(ADV)-nucleated microbubbles was assessed based on cardiac perfusion and cardiac functional parameters. No change in cardiac perfusion was observed when using droplets with the target concentrations below 1.5 × 10−4 mL/mL, either with orwithout ultrasound insonation of the droplets. Oxygen scavenging increased with increasing droplet target concentration. The ADV transition efficiency increased with increasing droplet concentration between 0.05 × 10−4 and 0.5 × 10−4 mL/mL and decreased for higher concentrations. The conclusion of this study was that ultrasound-triggered phase-shift perfluorobutane droplets effectively scavenge oxygen without causing significant embolization at concentrations below 1.5 × 10⁻⁴ mL/mL. Oxygen scavenging increased with higher droplet concentrations, whereas the transition efficiency of ADV reached the largest value at 0.5 × 10⁻⁴ mL/mL, indicating an optimal performance balancing safety and efficacy exists.