Microbubbles and ultrasound-mediated thrombolysis: a review of recent in vitro studies

Current treatment of acute ischemic stroke with recombinant tissue plasminogen activator (rtPA) is limited to a small percentage of patients due to exclusion criteria and side effects. Sonothrombolysis (ultrasound-mediated thrombolysis) is a new treatment strategy shown to be effective for clot lysis, particularly when combined with ultrasound contrast agents (UCAs). The present review surveys recent in vitro studies of sonothrombolysis (STL). Different UCAs and STL approaches are presented and, in particular, the involved mechanisms are discussed. Acoustic cavitations generate microstreaming and microjets at the clot surface leading to direct (clot damage) and/or indirect (enhancement of thrombolytic drug effect) clot destruction. Microbubble-based UCAs have been shown to greatly potentiate cavitation effects and reduce the required acoustic pressure. However, STL remains a complex process with multiple interactions between blood clots, ultrasound, UCAs and thrombolytic drugs. All these parameters have to he optimized with regard to efficacy and safety.