Sonothrombolysis with magnetically targeted microbubbles

Microbubble-enhanced sonothrombolysis is a promising approach to increase the safety and efficacy of current pharmacological treatments for ischemic stroke. Maintaining therapeutic concentrations of microbubbles and drugs at the clot site however poses a challenge. The objective of this study was to investigate the efficacy of magnetic microbubble targeting upon clot lysis rates in vitro. Retracted whole porcine blood clots were placed in a flow phantom of a partially occluded middle cerebral artery. The clots were treated with a combination of tissue plasminogen activator (0.75µg/mL), magnetic microbubbles (~107 microbubbles/mL), and ultrasound (0.5MHz, 630kPa peak rarefactional pressure, 0.2Hz pulse repetition frequency, 2% duty cycle). Magnetic targeting was achieved using a single permanent magnet element (0.08-0.38T and 12-140T/m in the region of the clot). The change in clot diameter was measured optically over the course of the experiment. Magnetic targeting produced a three-fold average increase in lysis rates and linear correlation was observed between lysis rate and total energy of acoustic emissions.