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Microbubble-enhanced sonothrombolysis is a promising approach to increasing the tolerability 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 effect 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 (0.75 µg/mL), magnetic microbubbles (∼107 microbubbles/mL) and ultrasound (0.5 MHz, 630-kPa peak rarefactional pressure, 0.2-Hz pulse repetition frequency, 2% duty cycle). Magnetic targeting was achieved using a single permanent magnet (0.08-0.38 T and 12-140 T/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 threefold average increase in lysis rates, and linear correlation was observed between lysis rate and total energy of acoustic emissions.

Original publication

DOI

10.1016/j.ultrasmedbio.2018.12.014

Type

Journal article

Journal

Ultrasound med biol

Publication Date

05/2019

Volume

45

Pages

1151 - 1163

Keywords

Clot, Drug delivery, Magnetic targeting, Microbubbles, Passive cavitation detection, Thrombolysis, Ultrasound, Animals, Disease Models, Animal, Fibrinolytic Agents, In Vitro Techniques, Microbubbles, Swine, Thrombolytic Therapy, Thrombosis, Tissue Plasminogen Activator, Ultrasonic Therapy