Intravascular Sonothrombolysis, in vitro, Using a Small Aperture, Forward-Viewing, Sub-Megahertz Transducer to Enhance tPA Treatment

Abstract

Catheter-based thrombolytic treatments with tissue plasminogen activator (tPA) have long treatment times (>15 hrs) and high risk of intracranial hemorrhage. Sonothrombolysis may improve patient outcomes while reducing the dose of tPA needed for treatment. We recently demonstrated a custom, forward-viewing intravascular (FVI) transducer with microbubbles (MBs) for in vitro sonothrombolysis. For clinical translation, we want to utilize this transducer to enhance tPA treatment. Therefore, the purpose of this study was to examine the thrombolytic outcomes of a forward-looking, IV transducer with tPA in vitro. Blood clots were treated for 30 minutes with either phosphate buffer saline (PBS), ultrasound (US) alone, tPA alone (1µg/ml), tPA + US, or MB + US (108 MB/ml). The percent clot lysis for the control group was 29 ± 4%, tPA alone was 29 ± 9%, and US alone was 25 ± 4%, with no statistically significant differences amongst these conditions. The percent clot lysis was 58 ± 10%, 59 ± 3% and 63 ± 5% for tPA + US and MB + US conditions respectively and both had statistically significantly more clot lysis than the control, US alone, or tPA alone groups. We have demonstrated that a forward-viewing intravascular transducer can be used to enhance tPA mediated sonothrombolysis and is comparable to microbubble mediated sonothrombolysis.