Ultrasound contrast agent enhances ultarsound assisted thrombolysis in stroke

描述（由申请人提供）： 急性缺血性中风的发生是由于血液凝块阻塞了大脑中的动脉。在缺血性中风中，更快地恢复营养血流大大提高了患者的生存机会，脑损伤最小，神经功能缺损的负担减轻。在症状发作后3小时内静脉注射rt-PA（重组组织纤溶酶原激活剂）是目前唯一获批的卒中治疗方法。我们认为，在存在超声的情况下，在血栓闭塞部位动脉内输送rt-PA和超声造影剂（UCA）的组合可以缩短缺血组织的再灌注时间。这种方法具有改善卒中治疗临床结局的潜力。EKOS MicroLysUS（R）输注系统是一种超声尖端血管内导管，其特征在于用于增强药物转运到血栓中。UCA是通常用于超声诊断成像的充气封装微泡。该项目的总体目标是在体内证明使用当前的EKOS超声导管同时输注市售的称为OptisonTM的UCA（Mallinckrodt Inc.，MO）和rt-PA（Genentech，CA）。EKOS导管将用于将UCA沿着药物直接输注到导管周围的直接血凝块体积中，并在其头端发出的声场中激活UCA气泡。我们的具体目标是：1.制定治疗方案以进行体内可行性研究：拟定的治疗包括在凝块中输注UCA。我们将研究临床相关凝块的孔径和OptisonTM微泡通过这些凝块的渗透性。这些信息将有助于设计一个方案，促进OptisonTM均匀渗透到凝块中，以产生一致的溶解增强。2.确定体内治疗方案的可行性：在犬基底动脉中形成自体血凝块。rt-PA和UCA的组合将在导管的入口点混合，并使用EKOS MicroLysUS（R）导管输送到凝块中。在治疗结束时，将进行再通时间、TIMI血流的血管造影评估和去凝分级评估，以确定拟定治疗方案的疗效。

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.