Science meets aesthetics in the Hossack Lab

 

Congratulations to Adam Dixon (PhD '16) whose work on using microfluidic technology to produce microbubbles for sonothrombolysis-based treatment of acute ischemic stroke will be featured on the April 2019 cover of Annals of Biomedical Engineering.

Hossack Lab Research on the Cover of April 2019 Annals of BME Journal

This figure illustrates the rat model used to evaluate the technology, in which stroke was simulated by injecting a blood clot into the rat brain to arrest blood flow, followed by treatment using ultrasound, microbubbles, and tissue plasminogen activator.

Efficacy of Sonothrombolysis Using Microbubbles Produced by a Catheter-Based Microfluidic Device in a Rat Model of Ischemic Stroke. Dixon AJ, Li J, Rickel JR, Klibanov AL, Zuo Z, Hossack JA. Ann Biomed Eng. 2019 Apr;47(4):1012-1022.

Abstract

Limitations of existing thrombolytic therapies for acute ischemic stroke have motivated the development of catheter-based approaches that utilize no or low doses of thrombolytic drugs combined with a mechanical action to either dissolve or extract the thrombus. Sonothrombolysis accelerates thrombus dissolution via the application of ultrasound combined with microbubble contrast agents and low doses of thrombolytics to mechanically disrupt the fibrin mesh. In this work, we studied the efficacy of catheter-directed sonothrombolysis in a rat model of ischemic stroke. Microbubbles of 10-20 µm diameter with a nitrogen gas core and a non-crosslinked albumin shell were produced by a flow-focusing microfluidic device in real time. The microbubbles were dispensed from a catheter located in the internal carotid artery for direct delivery to the thrombus-occluded middle cerebral artery, while ultrasound was administered through the skull and recombinant tissue plasminogen activator (rtPA) was infused via a tail vein catheter. The results of this study demonstrate that flow focusing microfluidic devices can be miniaturized to dimensions compatible with human catheterization and that large-diameter microbubbles comprised of high solubility gases can be safely administered intraarterially to deliver a sonothrombolytic therapy. Further, sonothrombolysis using intraarterial delivery of large microbubbles reduced cerebral infarct volumes by approximately 50% vs. no therapy, significantly improved functional neurological outcomes at 24 h, and permitted rtPA dose reduction of 3.3 (95% CI 1.8-3.8) fold when compared to therapy with intravenous rtPA alone.

About Adam Dixon

Adam Dixon (PhD BME 2016) is the Director of Clinical R&D at Rivanna Medical, a privately held medical device company located in Charlottesville, Virginia, and a Postdoc in John Hossack's Lab in the Department of Biomedical Engineering at the University of Virginia.