Ultrasound contrast agent enhances ultarsound assisted thrombolysis in stroke

超声造影剂增强中风超声辅助溶栓

基本信息

批准号：
7286824
负责人：
AZITA SOLTANI
金额：
$ 15.29万
依托单位：
EKOS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-15 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7286824
关键词：
Accounting Acoustics Acute Aftercare Age Alteplase Angiography Area Arteries Autologous Blood Blood - brain barrier anatomy Blood Clot Blood Platelets Blood Vessels Blood coagulation Blood flow Brain Brain Injuries Brain hemorrhage Budgets Canis familiaris Catheters Clinical Coagulation Process Condition Containment Contrast Media Control Groups Cytolysis Data Development Development Plans Devices Diagnostic Imaging Diagnostic Procedure Dose Drug Interactions Drug Transport Drug effect disorder Encapsulated Erythrocytes Feasibility Studies Fibrin Frequencies Gases Goals Grant Hour Human Image In Vitro Infusion procedures Injection of therapeutic agent Intravenous Investigation Ischemic Stroke Localized Location Lytic Measures Methods Microbubbles Modeling Monitor Neurologic Deficit Neuronal Injury Nutrient Outcome Oxygen Patients Penetration Performance Perfusion Personal Satisfaction Pharmaceutical Preparations Phase Physiological reperfusion Plasminogen Activator Procedures Protocols documentation Purpose Radial Range Rate Reperfusion Therapy Research Personnel Rupture Scanning Electron Microscopy Signal Transduction Site Stroke Symptoms System Technology Temperature Testing Therapeutic Thrombus Time Tissues Uca Ultrasonic Therapy Ultrasonics Ultrasonography United States Vascular System Vascular blood supply Visual Whole Blood base basilar artery brain size brain tissue clinically relevant cost effective design desire dosage electric impedance human subject improved in vivo intravenous injection local drug delivery middle cerebral artery neuroprotection novel therapeutics pre-clinical pressure programs restoration size soft tissue stroke therapy therapy outcome thrombolysis

项目摘要

DESCRIPTION (provided by applicant): 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 rt-PA (recombinant tissue plasminogen activator) within 3 hours of symptom onset is the only currently approved stroke therapy. We believe that Intra-arterial delivery of a combination of rt-PA and ultrasonic contrast agents (UCA) at the site of thromboocclusion in presence of ultrasound can shorten time to reperfusion of ischemic tissue. This approach holds the potential to improve clinical outcomes in stroke therapy. EKOS MicroLysUS(R) infusion system is an ultrasound-tipped intravascular catheter well characterized for use in enhancing drug transport into clots. UCAs are gas-filled, encapsulated microbubbles that are routinely used in ultrasound diagnostic imaging. The overall goal of this project is to demonstrate in vivo, feasibility of faster restoration of blood flow through a clot using current EKOS ultrasound catheter to simultaneously infuse a commercially available UCA called OptisonTM (Mallinckrodt Inc., MO) and rt-PA (Genentech, CA). The EKOS catheter will be used to infuse UCA along with drug directly in the immediate clot volume surrounding the catheter and activate the UCA bubbles in the acoustic field emitted from its tip. Our specific aims are: 1. Develop a therapeutic protocol for conducting an in vivo feasibility study: The proposed therapy involves infusion of UCA in the clot. We will investigate the pore size of clinically relevant clots and the penetration of OptisonTM microbubbles through these clots. This information will be pertinent in designing a protocol that facilitates uniform penetration of OptisonTM in a clot to generate consistent lysis enhancement. 2. To determine feasibility of the therapeutic protocol in vivo: An autologous clot will be formed in a canine basilar artery. A combination of rt-PA and UCA will be mixed at the entry point to the catheter and delivered into the clot using EKOS MicroLysUS(R) catheter. At the end of therapy, time to recanalization, angiographic assessment of TIMI flow and declotting grade assessment will be performed to determine efficacy of proposed therapeutic protocol.

描述（由申请人提供）：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RT-PA（重组组织纤溶酶原激活剂）是当前唯一批准的中风疗法。我们认为，在有超声的存在下，在血栓批判位点，RT-PA和超声造影剂（UCA）的动脉内输送可能会缩短缺血组织的再灌注。这种方法具有改善中风疗法临床结果的潜力。 Ekos Microlysus（R）输注系统是一种超声输出的血管内导管，其特征在于将药物运输到凝块中。 UCA是充满气体的，封装的微泡，通常用于超声诊断成像中。该项目的总体目的是证明体内，使用当前的Ekos超声导管通过凝块更快地恢复血液流动的可行性，同时注入称为optisontm（Mallinckrodt Inc.，Mo）和RT-PA（Genentech，Genentech，Genentech，genentech，genentech，genentech，genentech，genentech， CA）。 EKOS导管将用于直接在导管周围的直接凝块体积中注入UCA，并激活从其尖端发出的声场中的UCA气泡。我们的具体目的是：1。开发一种用于进行体内可行性研究的治疗方案：拟议的治疗涉及在凝块中输注UCA。我们将研究临床相关的凝块的孔径以及Optisontm Microbubbles通过这些凝块的渗透。该信息将与设计协议有关，该协议有助于凝块中optisontm均匀穿透以产生一致的裂解增强。 2。确定体内治疗方案的可行性：将在犬基底动脉中形成自体凝块。 RT-PA和UCA的组合将在导管的入口点混合，并使用Ekos Microlysus（R）导管递送到凝块中。在治疗结束时，将进行对TIMI流量的重新定性，血管造影评估和低年级评估的时间，以确定拟议的治疗方案的功效。