Dissolution of Thrombotic Arterial Occlusion by High Intensity, Low Frequency Ultrasound and Dodecafluoropentane Emulsion: An In Vitro and In Vivo Study

Objectives. We examined the effectiveness of the microbubbles of an echo contrast agent, dodecafluoropentane (DDFP) emulsion, to enhance low frequency ultrasound clot disruption in vitro and in vivo. Background. Ultrasound is reported to facilitate clot dissolution, and microbubbles could theoretically enhance ultrasound clot dissolution by augmenting cavitational effects. Methods. In vitro studies: The disruption rate of fresh human clots by ultrasound (24 kHz, 2.9 W/cm2) was examined in saline and DDFP emulsion. In vivo studies: Using rabbit iliofemoral thrombotic occlusion model, recanalization rate and histopathologic findings were compared among groups treated with DDFP emulsion alone, transcutaneous ultrasound (20 kHz, 1.5 W/cm2) alone and with DDFP emulsion and ultrasound combined. Results. The ultrasound clot disruption rate was significantly (p < 0.01) increased, from 72 ± 18% (mean ± SD) in saline to 98 ± 4% in DDFP emulsion in 3 min in vitro. No vessel was recanalized by DDFP emulsion alone (0%), and only single artery was patent after ultrasound treatment alone (9%). In contrast, 82% of iliofemoral arteries were angiographically recanalized after ultrasound treatment with DDFP emulsion. Histologically, the patent arteries had only minimal focal mural thrombus, with no evidence of vessel wall damage. However, substantial damage was observed in rabbit dermis and subcutaneous tissue. Conclusions. 1) DDFP emulsion, an echo contrast agent, significantly enhances the clot-disrupting effect of low frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion model. 2) This simple combination therapy has potential for clinical application in patients with thrombotic arterial occlusions.