A Novel Ultrasound Phased Array and Sonication Method for Stroke Treatments

描述（由申请人提供）：为了开发聚焦超声治疗的潜力，需要具有大量元件的大功率相控阵换能器。目前的方法有两个主要缺点。首先，单个阵列元件的电阻抗随着尺寸的减小而增大。其次，阵列不能为一些高级应用提供足够的声功率。我们已经发现了一种克服这两个限制的方法，并提出基于这种方法开发新的治疗超声相控阵技术。更具体地说，在本提案中，我们将开发一个基于该技术的中风治疗系统。在过去的十年中，尽管在急性卒中干预试验上花费了数百万美元，但只有在发病后3-6小时内打开阻塞动脉并再灌注缺血半暗带的策略被证明是有效的。临床研究表明，经颅超声和多普勒超声联合组织型纤溶酶原激活剂（tPA）可显著增加闭塞血管再通的患者数量。然而，目前使用多普勒超声暴露仍有大量患者的动脉闭塞不能得到解决。我们的假设是，使用相控阵应用器和来自CT扫描的患者特异性头骨信息的经颅超声可以更好地定位大脑内的超声能量，并且与现有方法相比，这将导致患者反应的进一步改善。超声能量在大脑内的精确定位也可以使超声单独使用而不需要溶栓剂，从而消除这些物质的潜在副作用。在此拨款期间要完成的具体任务是：第一，开发新的阵列技术；第二，开发用于治疗中风的超声系统；第三，测量所需频率范围内的头骨特性

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.