Neuroimaging of deep brain stimulation patients using safe MRI excitations

使用安全 MRI 激励对深部脑刺激患者进行神经成像

• 批准号: 8961104
• 负责人: Bastien Guerin
• 金额: $ 9.38万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-17 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8961104
• 关键词: 3D Print; Algorithms; Award; Biomedical Engineering; Brain; Brain imaging; Clinical; Collaborations; Data; Data Analyses; Data Quality; Data Set; Deep Brain Stimulation; Development; Devices; Disease; Dystonia; Electrodes; Electromagnetics; Essential Tremor; Ethylene Glycols; Evaluation; FDA approved; Fostering; Freedom; Functional Magnetic Resonance Imaging; Funding; Future; Gel; Goals; Grant; Head; Health; Heating; Human; Image; Implant; Institution; Knowledge; Lead; Location; MRI Scans; Magnetic Resonance Imaging; Major Depressive Disorder; Manufacturer Name; Maps; Measurement; Mental Depression; Mental disorders; Mentors; Modality; Modeling; Monitor; Morphologic artifacts; Motion; Movement Disorders; Muscle; Neurosciences; Obsessive-Compulsive Disorder; Parkinson Disease; Patients; Phase; Physiologic pulse; Pilot Projects; Play; Positioning Attribute; Postoperative Period; Property; Protocols documentation; Psychiatric therapeutic procedure; Psychometrics; Rain; Research; Research Personnel; Research Proposals; Resources; Safety; Scanning; Shadowing (Histology); Technology; Temperature; Thermometry; Time; Training; Training Programs; Work; absorption; base; bioimaging; bone; career; clinical efficacy; clinical practice; cohort; computer cluster; deep brain stimulation array; design; electric field; electrical property; ethylene glycol; human data; human tissue; implantation; in vivo imaging; innovation; interest; models and simulation; motor disorder; neuroimaging; new technology; next generation; preimplantation; programs; public health relevance; radio frequency; radiologist; research study; safety testing; simulation; skills; technology development; technology validation; tool; transmission process

 DESCRIPTION (provided by applicant): In this application, I propose a program of technology development and validation that will allow to safely image the brain of patients with deep brain stimulation (DBS) implants using magnetic resonance imaging (MRI). This new technology, which builds on my previous work on parallel transmit (pTx) pulse design and specific absorption rate (SAR) monitoring, will allow the vast array of MRI anatomical and functional sequences to be deployed for the first time in DBS patients. Although DBS is a common therapy of severe motion disorders such a dystonia and Parkinson disease and has shown promise for the treatment of some psychiatric disorders such as depression, its mechanisms of action are not understood. Moreover, anatomical targets of the DBS electrode are not yet established in the case of psychiatric disorders. MRI is an ideal modality to quantify the changes in the functional networks of the brain that occur during the DBS treatment. The program of technology development and validation proposed in this grant would leverage the unmatched potential of MRI for neuroimaging to DBS patients. To solve the safety problem of MRI in the presence of a DBS implant, I propose to design radio-frequency (RF) pulses using multiple transmit channels as opposed to only one as is done with the ubiquitous birdcage coil. I will study two cases in particular: A birdcage coil driven independently on its two quadrature ports (2 independent transmit channels) and an 8 channels pTx coil. As my preliminary results show (see Research Strategy section), the additional degrees-of-freedom of these two coils allow the pulse designer to "sculpt" the 3D electric field distribution so as to minimize it at the location f the implant. As a result, induced currents and SAR are minimized. There are also tremendous degrees-of-freedom in the RF pulse itself, which needs to be designed while explicitly constraining SAR at the implant location. To apply these tools in humans, I propose a comprehensive safety testing program combining electromagnetic simulations and temperature mapping in realistic 3D-printed head phantoms. I will collaborate closely with the FDA and Medtronics (manufacturer of the only FDA-approved DBS implants) on the safety evaluation of these RF approaches. In my final Aim, I propose to perform a pilot study in a few DBS patients in order to verify that the quality of the data obtained such low- SAR MRI protocols is adequate (image quality metrics detailed in the Research Strategy). This research proposal fits exactly my research background and interests and will allow me to reach my short term goal of becoming an independent investigator. A K99/R00 award would help me jumpstart a bioengineering career focused on solving clinically important problems using innovative imaging approaches. After the R00 phase, I will submit an R01 building on the work performed in this grant. This R01 application will use the technology developed in Aims 1 and 2 and will leverage the preliminary human data obtained in Aim 3. My ultimate goal is to use MRI to explain the mechanisms of action and guide the development of emerging DBS strategies such as close-loop DBS and DBS arrays with multiple electrodes. To facilitate my progression to a position of independence, I have designed with my mentors a training program involving coursework, specialized seminars and clinical shadowing that will provide me with basic knowledge in neuroscience and the clinical practice of DBS as well as skills in neuroimaging data analysis. This training is crucial or me to reach a position of independence. Indeed, it will allow to design and conduct (after the K99/R00 period) my own MRI experiment. Moreover, although I do not intent to become neuroscientist myself, basic training in neuroscience is needed for me to efficiently collaborate with colleagues in this field. During the K99 phase of the award, I will be mentored by world-leading experts in MRI safety (Dr. Wald), DBS design and evaluation (Dr. Bonmassar) and neuroimaging evaluation of DBS patients (Dr. Dougherty) as well as consultants from MGH, the FDA and Medtronics. This research will be performed at the A. A. Martinos Center for Biomedical Imaging, a world-leading institution for functional neuroimaging and the study of brain changes in health and disease. The project will greatly benefit from the unique resources of the Martinos Center, including large computer clusters for electromagnetic simulations and data analysis as well as a 3 T MRI Siemens "Skyra" scanner with parallel transmit capability. I will also use the unique resources of the MGH Division for Neurotherapeutics, including rooms for psychometric evaluation, DBS programming devices and a large DBS patient pool. This project will also take advantage of an MGH-lead $35 Million grant funded by DARPA and aiming at designing the next generation of closed-loop DBS electrodes. The goals of this K99 application and the DARPA grant are different but highly complementary (the DARPA effort focuses on the development of new DBS implant technology and contains no imaging of DBS patients). This collaboration framework will help me foster collaborations with world-class DBS researchers and will likely increase the impact and visibility of my own work.

 描述（由申请人提供）：在本申请中，我提出了一项技术开发和验证计划，该计划将允许使用磁共振成像（MRI）对植入深部脑刺激（DBS）的患者的大脑进行安全成像。它建立在我之前关于并行传输 (pTx) 脉冲设计和比吸收率 (SAR) 监测的工作的基础上，将首次在 DBS 患者中部署大量 MRI 解剖和功能序列，尽管 DBS 很常见。治疗DBS 电极可用于治疗肌张力障碍和帕金森病等严重运动障碍，并已显示出治疗抑郁症等某些精神疾病的前景，但其作用机制尚不清楚。此外，在精神疾病方面，DBS 电极的解剖目标尚未确定。 MRI 是量化 DBS 治疗期间发生的大脑功能网络变化的理想方式。本次资助中提出的技术开发和验证计划将利用 MRI 对 DBS 患者进行神经影像学的无与伦比的潜力。解决安全问题为了在存在 DBS 植入物的情况下进行 MRI 分析，我建议使用多个传输通道来设计射频 (RF) 脉冲，而不是像无处不在的鸟笼线圈那样仅使用一个传输通道，我将特别研究两种情况： 鸟笼线圈。正如我的初步结果所示（参见研究策略部分），这两个线圈的附加自由度允许脉冲设计者“塑造”3D 电场分布，使其在植入位置最小化。因此，射频脉冲本身也具有巨大的自由度。为了在人体中应用这些工具，我提出了一个综合的安全测试计划，将电磁模拟和温度映射结合在现实的 3D 打印头部模型中，我将与 FDA 和美敦力密切合作。 （唯一获得 FDA 批准的 DBS 植入物的制造商）对这些 RF 方法的安全性评估 在我的最终目标中，我建议对一些 DBS 患者进行试点研究，以验证所获得的数据质量是否如此之低。 - SAR MRI 协议足够了（研究策略中详细介绍了图像质量指标）。这项研究提案完全符合我的研究背景和兴趣，将使我能够实现成为一名独立研究者的短期目标。我跳跃开始专注于使用创新成像方法解决临床重要问题的生物工程职业 在 R00 阶段之后，我将提交基于本次资助中所开展工作的 R01 申请，该 R01 申请将使用目标 1 和 2 中开发的技术，并将利用目标 3 中获得的初步人体数据。我的最终目标是使用 MRI 来解释作用机制并指导新兴 DBS 策略（例如闭环 DBS 和具有多个电极的 DBS 阵列）的开发，以促进我的进展。为了能够独立地工作，我与导师一起设计了一个培训计划，包括课程作业、专业研讨会和临床见习，这将为我提供神经科学和 DBS 临床实践的基础知识以及神经影像数据分析的技能。事实上，它将使我能够设计和进行（在 K99/R00 时期之后）我自己的 MRI 实验。此外，尽管我本人并不打算成为神经科学家，但需要进行神经科学方面的基本培训。为了在该奖项的 K99 阶段，我将得到 MRI 安全性（Wald 博士）、DBS 设计和评估（Bonmassar 博士）以及 DBS 神经影像评估方面的世界领先专家的指导。这项研究将在 A. A. Martinos 生物医学成像中心进行，该中心是世界领先的功能神经成像和研究机构。该项目将极大地受益于马蒂诺斯中心的独特资源，包括用于电磁模拟和数据分析的大型计算机集群以及具有并行传输能力的 3 T MRI 西门子“Skyra”扫描仪。还将利用 MGH 神经治疗部门的独特资源，包括心理评估室、DBS 编程设备和大型 DBS 患者库。该项目还将利用 MGH 牵头的 3500 万美元拨款。由 DARPA 开发，旨在设计下一代闭环 DBS 电极 该 K99 申请和 DARPA 拨款的目标不同，但高度互补（DARPA 的工作重点是开发新的 DBS 植入技术，不包含 DBS 成像。该合作框架将帮助我促进与世界一流的 DBS 研究人员的合作，并可能提高我自己工作的影响力和知名度。