MRI-guided focused ultrasound for drug delivery and ablation of brain tumors

描述(申请人提供)：在过去的20年里，我们和其他人开发了经颅MRI引导的聚焦超声(TcMRgFUS)的基础，这是一项将对临床神经科学的方方面面产生深远影响的非侵入性技术。TcMRgFUS是一种颠覆性技术，可以改进或取代现有的治疗方法，并实现今天不可能的治疗方法。它从根本上背离了目前的治疗方法，涉及到广泛学科的专业知识。虽然超声波对中枢神经系统疾病的全部潜力还不是很清楚，但转变的过程已经开始了。我们的目标是建立这样一个计划，在这笔赠款的有效期内，加速和加强具有已证实潜力的新TcMRgFUS应用的临床翻译。只有在技术充分发展、被证明是安全的、并以最终形式实施具有重大临床影响的疗法的情况下，这种转换才能发生。我们建议开发一个大规模的五年计划，引导TcMRgFUS疗法用于脑癌的临床应用。我们已经开发了三个项目，可以进行转化神经外科(脑肿瘤的非热消融)和神经肿瘤学(针对脑转移瘤的靶向化疗药物输送)。在药物输送方面，我们将利用低能量的FUS脉冲暂时破坏血脑屏障，这克服了在大脑中使用大多数药物的主要单一限制。在一个项目中，我们将开发和验证新的方法来计划、指导和评估这一过程。在第二项计划中，我们已经制定了一项计划，将这项技术的一个应用--将抗癌药物输送到乳腺癌脑转移瘤中，达到准备进行安全性和有效性临床试验的程度。最后，在第三个项目中，我们将结合FUS和微气泡剂来实现非热消融，这是手术和放射外科的一种非侵入性替代方案。使用这种方法，我们可以在不使用电离辐射的情况下，几乎在大脑的任何地方消融组织体积，也不需要任何重复治疗的限制。在拨款结束时，我们的目标是完成将这些改变游戏规则的TcMRgFUS应用程序转移到患者身上所需的大规模工作，为未来在治疗脑瘤和其他中枢神经系统疾病方面的广泛应用铺平道路。

DESCRIPTION (provided by applicant): Over the past 20 years, we and others developed the fundamentals of transcranial MRI-guided focused ultrasound (TcMRgFUS), a noninvasive technology that will have a profound impact on all aspects of clinical neuroscience. TcMRgFUS is a disruptive technology that can improve upon or replace existing treatments and enable therapies that are not possible today. It is a radical departure from current treatment methods and involves expertise from a broad range of disciplines. While the full potential that ultrasound can have for disorders of the central nervous system is not widely known, the transformational process already begun. Our aim is to establish such a program to accelerate and intensify the clinical translation of new TcMRgFUS applications with a proven potential during the lifetime of this grant. Such translation can only happen if the technology is fully-developed, demonstrated to be safe, and implemented in a final form for therapies with major clinical impact. We propose to develop a large-scale, five-year program that will shepherd TcMRgFUS therapies to clinical use for brain cancer. We have developed three projects that can have transform neurosurgery (non-thermal ablation of brain tumors) and neurooncology (targeted drug delivery of chemotherapy to brain metastases). For drug delivery, we will utilize low-energy FUS bursts to temporarily disrupt the blood-brain barrier, which overcomes the major singular limitation of using most drugs in the brain. In one project, we will develop and validate new methods to plan, guide, and evaluate this procedure. In the second, we have developed a plan to move one application of this technology, delivery of anti-cancer agents to breast cancer brain metastases, to the point where it is ready for safety and efficacy clinical trials. Finally, in the third projet, we will combine FUS and a microbubble agent to enable non-thermal ablation, a noninvasive alternative to surgery and radiosurgery. With this method, we can ablate tissue volumes practically anywhere in the brain without using ionizing radiation and without any limits on repeated treatments. At the end of the grant, we aim to have completed the large-scale work needed to move these game-changing TcMRgFUS applications to patients, paving the way to future broad application in treating brain tumors and other disorders in the central nervous system.