Effects of acoustic parameters on sonothrombolysis with contrast microbubbles

This work aims at understanding some of the mechanisms involved in the combined effects of microbubbles, ultrasound exposure and recombinant tissue plasminogen activator (rtPA) on sonothrombolysis. It is based on a combination of experimental observations and a simple model to represent bubble destruction and lysis efficacy. Using an in vitro clot model and a single focused ultrasound beam, complex lysis patterns were observed following static exposure. It was hypothesized that these patterns reflect the role of the beam pressure profile in the presence of a flow of microbubbles subject to destruction/dissolution; separate parametric models for bubble destruction, clot lysis and flow profile were thus combined to represent the observed lysis profiles. Using parameter optimization, a reasonable agreement was found with the observed profiles during exposure, yielding at the same time estimates of bubble destruction parameters, lysis efficacy vs. pressure and bubble displacement during exposure. It is hoped that insight gained in this work may provide useful indications for optimizing schemes to achieve successful sonothrombolysis in vivo.