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: 8475981
• 负责人: Ferenc A Jolesz
• 金额: $ 130.07万
• 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/8475981
• 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 Therapy; Future; Grant; Human; Image; Ionizing radiation; Laboratories; 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; improved; innovation; malignant breast neoplasm; neuro-oncology; neurosurgery; novel strategies; novel therapeutic intervention; pre-clinical; preclinical study; programs; sound; tool; treatment planning; tumor

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 年里，我们和其他人开发了经颅 MRI 引导聚焦超声 (TcMRgFUS) 的基础知识，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治疗方法，并实现目前无法实现的治疗方法。它与当前的治疗方法截然不同，涉及广泛学科的专业知识。虽然超声波治疗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计划，以加速和加强新 TcMRgFUS 应用的临床转化，这些应用在本次拨款的有效期内已被证明具有潜力。只有当技术得到充分开发、被证明是安全的、并以最终形式实施以产生重大临床影响的疗法时，这种转化才能发生。我们建议开发一项为期五年的大规模计划，将 TcMRgFUS 疗法推向脑癌的临床应用。我们开发了三个项目，可以改变神经外科（脑肿瘤的非热消融）和神经肿瘤学（将化疗靶向递送至脑转移瘤）。对于药物输送，我们将利用低能量 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，我们将开发并验证新方法来规划、指导和评估这一过程。第二，我们制定了一项计划，推动这项技术的一项应用，即向乳腺癌脑转移瘤输送抗癌药物，使其为安全性和有效性临床试验做好准备。最后，在第三个项目中，我们将结合 FUS 和微泡剂以实现非热消融，这是手术和放射外科的非侵入性替代方案。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，并且对重复治疗没有任何限制。在资助结束时，我们的目标是完成将这些改变游戏规则的 TcMRgFUS 应用转移到患者身上所需的大规模工作，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。