Application of acoustic cavitation for thrombolysis in stroke

声空化在脑卒中溶栓中的应用

• 批准号: 7532851
• 负责人: AZITA SOLTANI
• 金额: $ 15.31万
• 依托单位: EKOS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7532851
• 关键词: Accounting; Acoustics; Activase; Acute; Acute myocardial infarction; Alteplase; Animals; Area; Arteries; Autologous; Blood; Blood Clot; Blood Vessels; Blood coagulation; Blood flow; Brain; Brain Injuries; Brain hemorrhage; Caliber; Canis familiaris; Cardiopulmonary; Catheters; Cell Nucleus; Clinical; Coagulation Process; Congestive Heart Failure; Contrast Media; Cytolysis; Devices; Diagnostic; Drug Transport; Drug effect disorder; Enzymes; Feasibility Studies; Fibrinolytic Agents; Frequencies; Gases; Generations; Goals; Hour; In Vitro; Infusion procedures; Intravenous; Investigation; Ischemic Stroke; Lasers; Learning; Liquid substance; Location; Lytic; Measures; Mechanics; Mediating; Microbubbles; Modality; Modeling; Neurologic Deficit; Neuronal Injury; Nutrient; Outcome; Output; Oxygen; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physiological reperfusion; Plasma; Plasminogen Activator; Population; Preparation; Protocols documentation; Purpose; Rate; Reperfusion Therapy; Respiratory Failure; Rupture; Site; Source; Stroke; Surface; Symptoms; System; Technology; Test Result; Testing; Therapeutic; Therapeutic Effect; Therapeutic procedure; Time; Tissues; Uca; Ultrasonic Therapy; Ultrasonography; United States; Unstable angina; Vascular blood supply; Water; basilar artery; brain size; brain tissue; concept; cost; design; dosage; improved; in vivo; intravenous administration; local drug delivery; neuroprotection; pre-clinical research; pressure; prototype; research study; restoration; size; stroke therapy; thrombolysis

DESCRIPTION (provided by applicant): EKOS Micro-infusion(r) system is an ultrasound-tipped microcatheter well characterized for use in enhancing drug transport into clots. We propose to modify the EKOS microcatheter by incorporating a Cavitation Promoting Surface (CPS). The overall goal of this project is to demonstrate feasibility of incorporating CPS in the microcatheter and obtaining significant enhancement in bioefficacy, in-vitro and in-vivo. The acoustic field emitted from the catheter tip will be used for active induction of cavitation from a CPS on the catheter tip while infusing the drug (t-PA, Activase(r)) directly in the immediate clot volume surrounding the catheter. Our specific aims are: 1. Investigate and incorporate CPS into the microcatheter device: We will identify and characterize the surface of materials that promote cavitation. These materials will then be exposed to ultrasound to learn acoustic parameters that consistently induce cavitation in blood. The CPS will be incorporated in the current microcatheter design and evaluated for thrombogenecity in vivo. 2. Determine bioefficacy in-vitro and in-vivo using CPS-incorporated microcatheter for t-PA delivery: The CPS-incorporated microcatheter will be tested for bioefficacy in-vitro and in-vivo. In-vitro testing will include well-established dynamic clot model that measures thrombolysis. Following demonstration of significant enhancement of thrombolysis by in-vitro tests, in-vivo bioefficacy tests will be conducted. An autologous clot will be formed in a canine basilar artery. t-PA will be delivered into the clot using current and CPS-incorporated microcatheters and exposed to ultrasound. At the end of therapy, time to recanalization determined angiographically will be used to determine bioefficacy. 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 t-PA (tissue plasminogen activator) within 3 hours of symptom onset is the only currently approved stroke therapy. We believe in combination with Intravenous administration, intra-arterial delivery of t-PA at the site of thromboocclusion in presence of ultrasound intensities sufficient to generate intrinsic cavitation can enhance the transport of drug into clots and shorten time to reperfusion of ischemic tissue. This approach holds the potential to improve clinical outcomes in stroke therapy.

描述（由申请人提供）：EKOS微输注(r)系统是一种超声尖端微导管，其特点是用于增强药物进入血栓的转运。我们建议通过加入空化促进表面（CPS）来改进EKOS微导管。该项目的总体目标是证明将CPS纳入微导管的可行性，并在体外和体内获得显著的生物功效增强。导管尖端发出的声场将用于主动诱导导管尖端CPS的空化，同时将药物（t-PA, Activase(r)）直接注入导管周围的直接凝块体积中。我们的具体目标是：1。研究并将CPS纳入微导管装置：我们将识别和表征促进空化的材料表面。然后，这些材料将暴露在超声波中，以了解持续引起血液空化的声学参数。CPS将被纳入目前的微导管设计，并评估体内血栓形成性。2. 测定体外和体内使用cps微导管给t-PA的生物功效：cps微导管将进行体外和体内生物功效测试。体外测试将包括完善的动态凝块模型来测量溶栓。在通过体外试验证明显著增强溶栓后，将进行体内生物功效试验。自体凝块会在犬基底动脉形成。t-PA将通过电流和cps结合的微导管输送到血栓中，并暴露在超声下。在治疗结束时，血管造影确定的再通时间将用于确定生物疗效。