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

MRI 引导聚焦超声用于药物输送和脑肿瘤消融

• 批准号: 9102026
• 负责人: Nathan J. McDannold
• 金额: $ 121.73万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-05 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9102026
• 关键词: Ablation; Acoustics; Adverse effects; Antineoplastic Agents; Area; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Diseases; Brain Neoplasms; Cellular Structures; Central Nervous System Diseases; Cessation of life; Clinical; Clinical Trials; Development; Devices; Discipline; Disease; Drug Delivery Systems; Drug usage; ERBB2 gene; Evaluation; Focused Ultrasound; Focused Ultrasound Therapy; Future; Grant; Human; Ionizing radiation; Location; Magnetic Resonance Imaging; Malignant neoplasm of brain; Mediating; Medicine; Metastatic malignant neoplasm to brain; Methods; Microbubbles; Modification; Monitor; Neuraxis; Neurosciences; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Procedures; Process; Publishing; Radiosurgery; Risk; Safety; Skull Base Neoplasms; Staging; Techniques; Technology; Testing; Thermal Ablation Therapy; Tissues; Translating; Translations; Ultrasonic Therapy; Ultrasonography; Work; chemotherapy; clinical efficacy; cranium; efficacy testing; efficacy trial; focus ultra; image guided; improved; innovation; laboratory equipment; malignant breast neoplasm; neuro-oncology; neurosurgery; novel strategies; novel therapeutic intervention; novel therapeutics; pre-clinical; preclinical study; programs; sound; tool; treatment planning; tumor ablation

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.

描述（由申请人提供）：在过去的20年中，我们和其他人开发了经颅MRI引导重点超声（TCMRGFUS）的基础，这是一种无创技术，将对临床神经科学的各个方面产生深远的影响。 TCMRGFUS是一种破坏性的技术，可以改善或取代现有治疗方法并实现今天无法使用的治疗方法。这是与当前治疗方法的根本性不同，涉及广泛学科的专业知识。尽管超声对中枢神经系统疾病的全部潜力尚不广泛，但转化过程已经开始。我们的目的是建立这样的计划，以加速和加强新的TCMRGFUS应用程序的临床翻译，并在这笔赠款的一生中具有可靠的潜力。这种翻译只有在技术完全开发，证明是安全的，并以最终的临床影响疗法的最终形式实施，才能发生这种翻译。我们建议开发一项大规模的五年计划，该计划将用于用于脑癌临床使用的TCMRGFUS疗法。我们已经开发了三个可以改变神经外科（脑肿瘤的非热消融）和神经科学（将化学疗法递送至脑转移的药物）的项目。对于药物输送，我们将利用低能的FUS爆发来暂时破坏血脑屏障，这克服了使用大脑中大多数药物的主要奇异限制。在一个项目中，我们将开发并验证新方法来计划，指导和评估此过程。在第二个方面，我们制定了一项计划，将这项技术的一种应用，将抗癌剂传递到乳腺癌脑转移酶中，以便为安全性和有效性临床试验做好准备。最后，在第三个Projet中，我们将结合FUS和微泡剂，以实现非热消融，这是一种无创手术和放射外科手术的无创替代品。使用这种方法，我们可以在不使用电离辐射的情况下消除大脑中任何地方的组织体积，而无需重复治疗而没有任何限制。在赠款结束时，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中所需的大规模工作，为未来在治疗中枢神经系统中的脑肿瘤和其他疾病方面铺平了道路。