Examining the Influence of Low-Dose Tissue Plasminogen Activator on Microbubble-Mediated Forward-Viewing Intravascular Sonothrombolysis.

Previous work revealed that a forward-viewing intravascular (FVI) transducer can be used for microbubble (MB)-mediated sonothrombolysis and that the clot lysis was dependent on MB concentration. This study examined the effects of combining tissue plasminogen activator (tPA) with MB-mediated FVI sonothrombolysis. In vitro clot lysis and passive cavitation experiments were conducted to study the effect of low-dose tPA in FVI sonothrombolysis with varying MB concentrations. Enhanced FVI sonothrombolysis was observed in cases in which ultrasound (US) was combined with tPA or MBs compared with control, tPA alone or US alone. The lysis rate of US + tPA + MBs was improved by up to 130%, 31% and 8% for MB concentrations of 106, 107 and 108 MBs/mL, respectively, compared with MBs + US alone. Changes in stable and inertial cavitation doses were observed, corresponding to changes in clot lysis in MB-mediated FVI sonothrombolysis with and without tPA.