Ultrasound contrast agent enhances ultarsound assisted thrombolysis in stroke

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DESCRIPTION (provided by applicant): Acute Ischemic Strokes occur due to blockage of an artery in the brain by a blood clot. In ischemic stroke faster restoration of nutrient blood flow greatly improves patient's chances of survival with minimum brain damage and reduced burden of neurologic deficits. Intravenously administered rt-PA (recombinant tissue plasminogen activator) within 3 hours of symptom onset is the only currently approved stroke therapy. We believe that Intra-arterial delivery of a combination of rt-PA and ultrasonic contrast agents (UCA) at the site of thromboocclusion in presence of ultrasound can shorten time to reperfusion of ischemic tissue. This approach holds the potential to improve clinical outcomes in stroke therapy. EKOS MicroLysUS(R) infusion system is an ultrasound-tipped intravascular catheter well characterized for use in enhancing drug transport into clots. UCAs are gas-filled, encapsulated microbubbles that are routinely used in ultrasound diagnostic imaging. The overall goal of this project is to demonstrate in vivo, feasibility of faster restoration of blood flow through a clot using current EKOS ultrasound catheter to simultaneously infuse a commercially available UCA called OptisonTM (Mallinckrodt Inc., MO) and rt-PA (Genentech, CA). The EKOS catheter will be used to infuse UCA along with drug directly in the immediate clot volume surrounding the catheter and activate the UCA bubbles in the acoustic field emitted from its tip. Our specific aims are: 1. Develop a therapeutic protocol for conducting an in vivo feasibility study: The proposed therapy involves infusion of UCA in the clot. We will investigate the pore size of clinically relevant clots and the penetration of OptisonTM microbubbles through these clots. This information will be pertinent in designing a protocol that facilitates uniform penetration of OptisonTM in a clot to generate consistent lysis enhancement. 2. To determine feasibility of the therapeutic protocol in vivo: An autologous clot will be formed in a canine basilar artery. A combination of rt-PA and UCA will be mixed at the entry point to the catheter and delivered into the clot using EKOS MicroLysUS(R) catheter. At the end of therapy, time to recanalization, angiographic assessment of TIMI flow and declotting grade assessment will be performed to determine efficacy of proposed therapeutic protocol.