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

描述（由申请人提供）：在过去的20年里，我们和其他人开发了经颅mri引导聚焦超声（TcMRgFUS）的基础，这是一种非侵入性技术，将对临床神经科学的各个方面产生深远的影响。TcMRgFUS是一项颠覆性技术，可以改进或取代现有的治疗方法，并使目前无法实现的治疗成为可能。这是对当前治疗方法的彻底背离，涉及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尚未广为人知，但转变过程已经开始。我们的目标是建立这样一个项目，以加速和加强具有已证实潜力的新TcMRgFUS应用的临床转化。只有当技术得到充分发展，证明是安全的，并以具有重大临床影响的最终形式实施治疗时，这种转化才能发生。我们建议开发一个大规模的、为期五年的项目，将TcMRgFUS疗法应用于脑癌的临床治疗。我们已经开发了三个项目，可以转化神经外科（脑肿瘤的非热消融）和神经肿瘤学（靶向药物输送化疗到脑转移）。对于药物输送，我们将利用低能量的FUS爆发来暂时破坏血脑屏障，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，我们将开发并验证计划、指导和评估该过程的新方法。其次，我们制定了一项计划，将这项技术的一项应用，即向乳腺癌脑转移灶输送抗癌药物，推向安全性和有效性临床试验的阶段。最后，在第三个项目中，我们将结合FUS和微泡剂来实现非热消融，这是一种非侵入性的替代手术和放射手术的方法。通过这种方法，我们可以在不使用电离辐射的情况下消融大脑中几乎任何地方的组织体积，也没有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应用于患者所需的大规模工作，为未来在治疗脑肿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.