Ultrasound-Targeted Therapy for Acute Myocardial Infarction

描述（由申请人提供）：急性心肌梗死是发达国家的主要死因之一，甚至在发展中国家也正在迅速成为主要死因。如果患者可以进入一家有24小时介入医生的医院，则在胸痛发作后90-120分钟内打开梗死相关动脉（伊拉）的机会为85%。即使在美国，大多数患者也无法使用这些设施，如果他们到达地区医院，可能会接受溶栓治疗，其成功率为60%。如果其他一些非侵入性和易于应用的治疗方法可以提高单独使用溶栓剂的成功率，并使其接近经皮冠状动脉介入治疗的85%，那么它可能会对公共卫生产生重大影响。本提案的总体目标是开发新型超声器械技术，用于微泡超声介导治疗急性心肌梗死。 本提案的具体目标是开发一种集成的体内治疗成像系统，以：1。使用狒狒的血管分流模型确定导致体内成功溶栓的最佳超声参数。 2.开发可向血栓输送适当超声能量的治疗探头，以溶解血栓并减少再灌注后的微血栓栓塞。 3.将治疗探头与4D超声成像系统集成，该系统可以对体内微泡进行成像，并门控超声脉冲以自动溶解血栓。 4.探讨急性冠状动脉闭塞时心肌微循环的机制，并通过超声治疗心肌预防再灌注后的微血栓栓塞。 该提案是关于生物医学研究伙伴关系的，涉及该国在其特定领域的领导人。Steve Hanson博士（OHSU）是血栓形成方面的专家，他使用创新的狒狒模型来研究血栓溶解。托马斯波特博士（内布拉斯加大学）是使用微泡和超声溶解动脉血栓的先驱。Robert Siegel，MD（Cedars-Sinai，UCLA）描述了在急性冠状动脉闭塞期间超声直接心肌保护的新发现，该发现与其对血栓的影响无关。Sanjiv Kaul，MD（OHSU）是MCE领域的先驱，并开发了评估微循环的复杂技术，包括无复流测量、定量局部心肌灌注和分子成像。Pierre Khuri-Yakub（斯坦福大学）是传感器技术的领导者，GE是超声系统的世界领导者。Xubo Song（OHSU）是确定性跟踪算法的权威，该算法可以帮助将超声输送到跳动心脏中的正确目标。 公共卫生相关性：急性心肌梗死（心脏病发作）是发达国家的主要死因之一，甚至在发展中国家也正在迅速成为主要死因。该提案的目的是开发一种超声系统，该系统可以非侵入性地并且容易地溶解导致梗塞的冠状动脉内的凝块，并且治疗由于凝块而不接收血液的组织。在这一建议中，我们召集了世界各国在各自领域的专家来开发这样一个系统。

DESCRIPTION (provided by applicant): Acute myocardial infarction is one of the leading causes of death in the developed world and is fast becoming a leading cause of death even in the developing world. If a patient has access to a hospital with interventionalists on 24 hr a day call, the chances of opening an infarct-related artery (IRA) within 90-120 minutes of the onset of chest pain is 85%. Most patients, even in the US, do not have access to such facilities and if they arrive at a regional hospital are likely to receive thrombolytic therapy that has a success rate of 60% in opening the infarct-related artery. If some other non-invasive and easily applied treatment could enhance the success of thrombolytics alone and bring it closer to the 85% that can be achieved with percutaneous coronary interventions, it could have a major public health impact. The overall aim of this proposal is to develop novel ultrasound device technologies for microbubble-ultrasound mediated treatment of acute myocardial infarction. The specific aims of this proposal are to develop an integrated in vivo therapy-imaging system to: 1. Determine the optimal ultrasound parameters that cause successful thrombolysis in vivo using a vascular shunt model in baboons. 2. Develop therapy probe(s) that can deliver appropriate ultrasound energy to the thrombus in order to dissolve it and reduce microthromboembolism after reperfusion. 3. Integrate the therapy probe(s) with a 4D ultrasound imaging system that can image microbubbles in vivo and gate ultrasound pulses to automatically dissolve the thrombus. 4. Determine the mechanisms of myocardial microcirculation during acute coronary occlusion and prevent microthromboembolism after reperfusion by treating the myocardium with ultrasound. This proposal is for a Biomedical Research Parternership that involves the leaders in the country in their specific fields. Steve Hanson, PhD (OHSU) is an expert on thrombosis and has used innovative baboon models to study thrombolysis. Thomas Porter, MD (University of Nebraska) is a pioneer in the use of microbubbles and ultrasound for arterial thrombus dissolution. Robert Siegel, MD (Cedars-Sinai, UCLA) has described the novel findings of direct myocardial protection by ultrasound during acute coronary occlusion that is independent of its effect on the thrombus. Sanjiv Kaul, MD, (OHSU) has pioneered the field of MCE and has developed sophisticated techniques to assess the microcirculation, including measurement of no reflow, quantifying regional myocardial perfusion, and molecular imaging. Pierre Khuri-Yakub (Stanford) is a leader in transducer technology, and GE is a world leader in ultrasound systems. Xubo Song (OHSU) is an authority on deterministic tracking algorithms that can assist in delivery of ultrasound to the correct target in a beating heart. PUBLIC HEALTH RELEVANCE: Acute myocardial infarction (heart attack) is one of the leading causes of death in the developed world and is fast becoming a leading cause of death even in the developing world. The aim of this proposal is to develop an ultrasound system that can non-invasively and easily dissolve the clots within a coronary artery responsible for an infarction and treat the tissue that is not receiving blood because of the clot. In this proposal we have brought together world experts in their respective fields to develop such a system.