A Novel Ultrasound Phased Array and Sonication Method for Stroke Treatments

用于中风治疗的新型超声相控阵和超声处理方法

基本信息

批准号：
8319219
负责人：
Kullervo Hynynen
金额：
$ 39.21万
依托单位：
SUNNYBROOK & WOMEN'S COLL HLTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319219
关键词：
Acoustics Adverse effects Alteplase Animal Model Arteries Beryllium Blood Vessels Bone Density Brain Caring Clinical Research Clinical Treatment Clinical Trials Coagulation Process Development Doppler Ultrasound Elements Fibrinolytic Agents Focused Ultrasound Therapy Frequencies Grant Hour Human Image Individual Intervention Trial Ischemic Penumbra Link Magnetic Resonance Imaging Measurement Methods Microbubbles Modeling Motion Patient Care Patients Phase Positioning Attribute Preclinical Testing Property Radiation Research Role Shapes Simulate Sonication Speed Stroke System Technology Testing Therapeutic Tissues Toxic effect Transducers Tubular formation Ultrasonic Therapy Ultrasonography X-Ray Computed Tomography absorption acute stroke artery occlusion base bone cranium density electric impedance in vivo in vivo Model new technology novel prototype public health relevance research study response thrombolysis treatment planning vasoconstriction

项目摘要

DESCRIPTION (provided by applicant): In order to exploit the potential of focused ultrasound therapy, high-power phased array transducers with large number of elements are required. Current methods have two major drawbacks. First, the electrical impedance of individual array elements becomes large as their size is reduced. Second, arrays are not able to deliver adequate acoustic power for some advanced applications. We have discovered a method to overcome both of these limitations and propose to develop new phased array technology for therapeutic ultrasound based on this approach. More specifically in this proposal we will develop a system based on this technology for the treatment of stroke. Despite millions of dollars spent on acute stroke intervention trials over the last decade, only strategies that open blocked arteries and reperfuse ischemic penumbra within 3-6 hours of onset have proven to be effective. Clinical studies have shown that transcranial ultrasound and Doppler ultrasound can significantly increase the number of patients that will have recanalization of the occluded vessel when administrated together with tissue plasminogen activator (tPA). However, there are still a large number of patients whose arterial occlusion is not resolved with the current use of Doppler ultrasound exposure. It is our hypothesis that transcranial sonication using phased array applicators and patient-specific skull information derived from CT scans can better localize ultrasound energy within the brain, and that this will result in further improvements in patient response as compared with existing approaches. Precise localization of ultrasound energy within the brain could also enable the use of ultrasound alone without a thrombolytic agent thus eliminating the potential side effects of these substances. The specific tasks to be completed during this grant period are: First, development of the new array technology, second, development of an ultrasound system for the treatment of stroke, third, measurements of skull properties at the required frequency range, and fourth, tests of the complete system with ex vivo human skulls. In addition we will determine the optimal ultrasound exposures for the stroke treatments with and without tPA using ex vivo and in vivo models. Finally, we will test the short and long term impact of the treatments in two different animal models. At the end of this research we will have developed a phased array technology that can overcome the remaining barriers in applying this technology optimally for ultrasound therapy. In addition we will have completed a prototype system and will have conducted pre-requisite preclinical testing to be in a position for subsequent clinical trials for the treatment of acute stroke. Public Health Relevance Statement (provided by applicant): Despite millions of dollars spent on acute stroke intervention trials over the last decade, only strategies that open blocked arteries and reperfuse ischemic penumbra within 3-6 hours of onset have proven to be effective. Only a few percent of all stroke patients receive clot-busting treatments, however, due to the system requirements to deliver appropriate care. It is our hypothesis that a larger number of patients could benefit from these treatments if advanced phased array systems are used to accelerate thrombolysis. The phased arrays would allow predictable ultrasound exposures and minimize impact on the surrounding tissues. During this research we plan to develop such a system and perform all of the experiments needed prior to starting clinical trials. This research may have a major impact on patient care.

描述（由申请人提供）：为了利用聚焦超声治疗的潜力，需要大量元素的高功率阶数换能器。当前方法有两个主要缺点。首先，随着尺寸降低，单个阵列元件的电阻抗变得很大。其次，阵列无法为某些高级应用提供足够的声学能力。我们发现了一种克服这两种局限性的方法，并建议根据这种方法为治疗性超声开发新的分阶段阵列技术。更具体地说，在此提案中，我们将开发一种基于该技术治疗中风的系统。尽管在过去十年中花费了数百万美元用于急性中风干预试验，但仅在发作后3-6小时内，只有开放式动脉和reperfuse缺血性阴茎的策略已被证明是有效的。临床研究表明，当与组织纤溶酶原激活剂（TPA）一起管理时，经颅超声和多普勒超声可以显着增加闭塞血管的患者数量。但是，仍然有大量患者的动脉阻塞并未通过目前使用多普勒超声暴露而解决。我们的假设是，使用分阶段阵列涂抹器和从CT扫描得出的患者特异性颅骨信息进行经颅超声处理可以更好地将超声波能量定位在大脑中，并且与现有方法相比，这将导致患者反应的进一步改善。超声在大脑中的精确定位也可以仅用溶栓剂就可以单独使用超声波，从而消除了这些物质的潜在副作用。在此赠款期间要完成的特定任务是：首先，开发新阵列技术，其次，开发了中风治疗的超声系统，第三，在所需频率范围内的颅骨特性测量以及第四，与体内颅骨的完整系统测试。此外，我们将使用离体和体内模型确定有或没有TPA的中风处理的最佳超声暴露。最后，我们将测试两种不同动物模型中治疗的短期和长期影响。在这项研究结束时，我们将开发出一个分阶段的阵列技术，该技术可以克服最佳地应用该技术进行超声治疗的剩余障碍。此外，我们将完成一个原型系统，并将进行先决条件的临床前测试，以便随后进行临床试验以治疗急性中风。公共卫生相关声明（由申请人提供）：尽管在过去十年中花费了数百万美元在急性中风干预试验上，但仅在发病后3-6小时内开放的动脉和替代性缺血性阴茎才能有效。但是，由于系统要求提供适当的护理，只有几个中风患者接受了凝块破坏治疗。我们的假设是，如果使用先进的阶段阵列系统来加速溶栓，则大量患者可以从这些治疗中受益。分阶段阵列将允许可预测的超声曝光，并最大程度地减少对周围组织的影响。在这项研究中，我们计划开发这样的系统，并在开始临床试验之前执行所需的所有实验。这项研究可能会对患者护理产生重大影响。