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微灌注（R）系统是一种超声波的微导管，旨在将药物运输到凝块中。我们建议通过结合促进表面（CPS）来改变EKOS微型导管。该项目的总体目标是证明将CP纳入微量导管并获得生物效能，体外和体内的可行性。从导管尖端发出的声场将用于从导管尖端上的CPS积极诱导，同时将药物（T-PA，Activans（r））直接在导管周围的凝块量中直接注入。我们的具体目的是：1。调查并将CPS纳入微导管设备：我们将识别并表征促进空化的材料表面。然后，这些材料将暴露于超声波中，以学习一贯诱导血液中气蚀的声参数。 CPS将纳入当前的微型导管设计中，并在体内评估血栓基因。 2。使用CPS合并的微型导管进行T-PA递送确定体外和体内的生物效能：将测试与CPS的微型导管进行测试，以实现生物效能感中的生物效能体内和体内。体外测试将包括测量溶栓的良好动态凝块模型。在证明通过体外测试对溶栓的显着增强后，将进行体内生物效能测试。自体凝块将在犬基底动脉中形成。 T-PA将使用电流和包含CPS的微心理器将T-PA传递到凝块中，并暴露于超声。在治疗结束时，在血管造影上确定重新定性的时间将用于确定生物效能。 急性缺血性中风是由于血块在大脑中阻塞的动脉阻塞而发生的。在缺血性中风中，养分血流的更快恢复可大大提高患者的生存机会，并减少脑损伤和神经系统缺陷的负担减轻。症状发作3小时内静脉内给药的T-PA（组织纤溶酶原激活剂）是当前唯一批准的中风治疗。我们相信，与静脉内给药相结合，在存在足以产生固有空化的超声强度的情况下，动脉内T-PA在血栓结咬的部位上递送T-PA，可以增强药物的运输，并缩短缺血性组织的再灌注时间。这种方法具有改善中风疗法临床结果的潜力。