Ultrasound-Targeted Therapy for Acute Myocardial Infarction

描述(申请人提供)：急性心肌梗塞是发达国家的主要死亡原因之一，甚至在发展中国家也正在迅速成为主要的死亡原因。如果患者可以在24小时全天候与干预者一起前往医院，则在胸痛发作后90-120分钟内打开梗塞相关动脉(IRA)的可能性为85%。即使在美国，大多数患者也无法使用这样的设施，如果他们到达地区医院，很可能会接受溶栓治疗，其打开梗塞相关动脉的成功率为60%。如果其他一些非侵入性且易于应用的治疗方法能够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所能达到的85%，那么它可能会对公众健康产生重大影响。该提案的总体目标是开发新的超声设备技术，用于微泡超声介导的急性心肌梗死治疗。这项建议的具体目的是开发一种一体化的体内治疗-成像系统，以：1.利用狒狒的血管分流模型，确定能够在体内成功溶解血栓的最佳超声参数。2.研制治疗探头(S)，能将适量的超声能量传递给血栓，以溶解血栓，减少再通后的微血栓栓塞。3.将治疗探头(S)与4D超声成像系统集成在一起，该系统可以对体内的微泡进行成像，并选通超声脉冲来自动溶解血栓。4.探讨急性冠脉闭塞时心肌微循环的变化机制，并通过超声治疗预防再灌注后微血栓的形成。这项提议是为了建立一个生物医学研究伙伴关系，让该国特定领域的领导人参与进来。史蒂夫·汉森博士(OHSU)是血栓形成方面的专家，他曾使用创新的狒狒模型来研究血栓溶解。托马斯·波特医学博士(内布拉斯加州大学)是使用微泡和超声波溶解动脉血栓的先驱。加州大学洛杉矶分校Cedars-Sinai医学博士Robert Siegel描述了超声在急性冠状动脉闭塞期间直接心肌保护的新发现，该发现独立于其对血栓的影响。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，包括测量无复流、量化局部心肌灌注和分子成像。Pierre Khuri-Yakub(斯坦福)是换能器技术的领导者，GE是超声波系统的世界领导者。宋旭波(OHSU)是确定性跟踪算法方面的权威，该算法可以帮助将超声波传递到心脏跳动中的正确目标。 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亡原因之一，甚至在发展中国家也正在迅速成为主要的死亡原因。这项提议的目的是开发一种超声系统，该系统可以无创地、容易地溶解导致梗塞的冠状动脉内的血栓，并治疗因血栓而无法接受血液的组织。在这项提议中，我们召集了各自领域的世界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.