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 Micro-infusion(r) 系统是一种超声头微导管，其特点是用于增强药物输送到血栓中。我们建议通过合并空化促进表面 (CPS) 来修改 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生物功效的显着增强。从导管尖端发出的声场将用于主动诱导导管尖端上的 CPS 产生空化，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 CPS 并将其纳入微导管装置中：我们将识别并表征促进空化的材料表面。然后，这些材料将暴露在超声波下，以了解持续诱发血液中空化现象的声学参数。 CPS 将纳入当前的微导管设计并评估体内血栓形成性。 2. 使用包含 CPS 的微导管进行 t-PA 输送，确定体外和体内的生物功效：将测试包含 CPS 的微导管的体外和体内生物功效。体外测试将包括用于测量血栓溶解的完善的动态血栓模型。通过体外试验证明溶栓效果显着增强后，将进行体内生物功效试验。自体血块将在犬基底动脉中形成。 t-PA 将使用现有的 CPS 微导管输送到凝块中，并暴露在超声波下。在治疗结束时，通过血管造影确定的再通时间将用于确定生物功效。 急性缺血性中风是由于脑部动脉被血凝块堵塞而发生的。在缺血性中风中，营养血流的更快恢复大大提高了患者的生存机会，同时最大限度地减少了脑损伤并减轻了神经功能缺损的负担。在症状出现后 3 小时内静脉注射 t-PA（组织纤溶酶原激活剂）是目前唯一批准的中风治疗方法。我们相信，与静脉给药相结合，在超声强度足以产生内在空化的情况下，在血栓闭塞部位动脉内输送 t-PA 可以增强药物向凝块的转运，并缩短缺血组织的再灌注时间。这种方法有可能改善中风治疗的临床结果。