Ultrasound-Targeted Therapy for Acute Myocardial Infarction

急性心肌梗死的超声靶向治疗

• 批准号: 8126485
• 负责人: SANJIV KAUL
• 金额: $ 80.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8126485
• 关键词: Acute; Acute myocardial infarction; Algorithms; Arteries; Biomedical Research; Blood; Blood Circulation; Blood Vessels; Blood flow; Cardiac; Cause of Death; Cell Nucleus; Chest Pain; China; Coagulation Process; Communicable Diseases; Congestive Heart Failure; Coronary; Coronary Occlusions; Coronary Thrombosis; Coronary artery; Country; Devices; Diagnosis; Dilatation - action; Doctor of Philosophy; Dose; Edema; Endothelial Cells; Fibrinolytic Agents; Frequencies; Heart; Hospitals; Image; In Situ; In Vitro; India; Infarction; Inferior; Intervention; Ischemia; Left; Limb structure; Liquid substance; Location; Measurement; Mediating; Microbubbles; Microcirculation; Modeling; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial perfusion; Myocardium; Nebraska; Necrosis; Nitric Oxide; Outcome; Papio; Patients; Peripheral; Physiologic pulse; Platelet aggregation; Play; Public Health; Recurrence; Reperfusion Therapy; Reporting; Role; Shunt Device; Site; Spasm; Surface; System; Techniques; Technology; Therapeutic; Thrombolytic Therapy; Thrombosis; Thrombus; Time; Tissues; Transducers; Ultrasonic Therapy; Ultrasonography; Universities; Ventricular; authority; cerebral artery; improved; in vivo; innovation; interest; men; molecular imaging; mortality; novel; percutaneous coronary intervention; prevent; public health relevance; respiratory; sound; success; therapy development; thrombolysis; trend

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.

描述（由申请人提供）：急性心肌梗塞是发达国家的主要原因之一，甚至在发展中国家也迅速成为主要的死亡原因。如果患者可以每天 24 小时前往有介入医生的医院，则在胸痛发作后 90-120 分钟内打开梗塞相关动脉 (IRA) 的几率为 85%。即使在美国，大多数患者也无法使用此类设施，如果他们到达地区医院，很可能会接受溶栓治疗，这种治疗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溶栓治疗的成功率，并使之接近经皮冠状动脉介入治疗所能达到的 85%，那么它可能会对公共健康产生重大影响。该提案的总体目标是开发新型超声设备技术，用于微泡超声介导的急性心肌梗死治疗。 该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. 开发能够向血栓提供适当超声能量以溶解血栓并减少再灌注后微血栓栓塞的治疗探头。 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.通过超声处理心肌，确定急性冠状动脉闭塞时心肌微循环的机制，预防再灌注后的微血栓栓塞。 该提案是针对生物医学研究合作伙伴关系，涉及该国特定领域的领导者。 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。 Thomas Porter 医学博士（内布拉斯加大学）是使用微泡和超声波溶解动脉血栓的先驱。 Robert Siegel 医学博士（加州大学洛杉矶分校雪松西奈分校）描述了在急性冠状动脉闭塞期间超声直接保护心肌的新发现，该保护与其对血栓的影响无关。 Sanjiv Kaul 医学博士 (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（斯坦福大学）是换能器技术的领导者，而 GE 是超声系统的世界领导者。 Xubo Song (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送到跳动心脏中的正确目标。 公共卫生相关性：急性心肌梗塞（心脏病发作）是发达国家的主要原因之一，甚至在发展中国家也迅速成为主要的死亡原因。该提案的目的是开发一种超声系统，能够无创且轻松地溶解导致梗塞的冠状动脉内的凝块，并治疗因凝块而无法接受血液的组织。在这个提案中，我们聚集了各自领域的世界专家来开发这样一个系统。