Improved imaging of deep brain nuclei with 7 Tesla MRI using comprehensive magnetic field monitoring and compensation

项目摘要/摘要： 中脑和间脑(丘脑、下丘脑、脑干等)的小核团网络。和 它们与大脑皮层的联系对于理解意识和镇静起效至关重要。 麻醉。然而，尽管它们对日常生存很重要，但核和核之间的功能联系 细胞核和皮质之间的关系仍然知之甚少。7特斯拉(7T)或以上的超高场MRI可提供 研究人类大脑深部核团的几个好处，包括改善图像信噪比 (SNR)和改进的对比度(CNR)，用于基于磁化率的结构(SWI)和功能(BOLD)成像，如 以及更大的T1离散度。除了由它们的小尺寸引起的问题外，对7T原子核的研究 受到这些位置的背景磁场(B0)的静态和动态变化的阻碍。 这些B0变化会导致图像伪影，如重影、信号空洞、模糊和几何失真。 ΔB0 订购并且不能补偿动态ΔB0。在当前的项目中，我们提出了一个全面的领域 创新：商用核磁共振扫描仪上的标准B0垫片线圈只能补偿静电 最高排名第二 监测和控制系统，在7T时消除高空间阶静动场变化。系统 将使用集成的RF-垫片线圈元件以实现最大的垫片和RF效率，将核磁共振现场探头用于现场 用于实时垫片更新的监控和反馈控制。我们是第一个将这些结合在一起的 技术在统一的系统中能够在很大程度上克服ΔB0在7T磁共振成像中的障碍。 验证：我们使用建议的系统来(a.)降低B0不均匀性的标准差 基于全脑的切片优化基础；(B)稳定EPI时间序列数据的阶段；(C)缓解 多镜头计划免疫中的重影；(D)成像并识别脑干和大脑之间的已知功能网络 单一受试者的大脑皮质；和(E)根据麻醉剂作用的动物模型检验一个假说 右旋美托咪定在涉及三个特定核团的脑干环路上。临床益处：通过提供一种新的 研究镇静期间脑干核团活动的工具，该项目为未来的努力铺平了道路 提高我们对神经回路的理解，开发更安全的定位麻醉药，并有可能 减少术后精神错乱和认知障碍。 培训：我有幸成为麻省理工学院异常丰富的神经成像环境的一部分 马蒂诺斯中心，世界上开发和验证拟议油田的首要环境之一 控制技术。我的K99/R00计划旨在帮助我从核磁共振物理学家转向 具有足够神经生物学背景的独立调查者，能够提出有临床意义的问题 涉及大脑深层电路，然后开发有针对性的高场磁共振技术来回答这些问题。为此， 我将需要额外的培训，课程作业，和K99阶段的导师，重点是功能磁共振， 神经科学、生理学和药理学。结构化培训将包括课程作业、教程、 研讨会、神经成像研讨会和临床暴露。培训计划包括以下内容： 1.继续由劳伦斯·沃尔德博士指导物理学和硬件先生 2.在Jonathan Polimeni博士和Marta博士的指导下，进行功能磁共振数据采集和分析方面的培训 Bianciardi关于超高场fMRI数据的研究，以及兰迪·巴克纳博士和Vitaly Napadow博士的帮助 功能连通性分析。 3.神经科学和生理学课程以及脑干核团和相关的指导性研究 由埃默里·布朗博士、布莱恩·埃德洛博士和维塔利·纳帕多博士领导的唤醒通路中的电路。 4.布朗博士在设计和实施麻醉研究方面的药理学课程和指导 以及在更广泛的人类生理学背景下了解药物对脑干的作用。 5.出席年度会议，包括ISMRM和HBM。 6.参加BrainMap神经成像系列研讨会和MGH放射学大赛。 7.来自我的主要导师的职业指导，包括关于拨款撰写和教师求职的建议。 我相信这个基金会将使我能够有效地与神经科学家和临床医生在 神经成像研究以前所未有的细节描绘了脑干的解剖和功能。 向独立过渡：我在硬件和核磁共振物理方面的深厚背景，结合我的 培训和指导计划，将使这个项目的成功和我随后过渡到 独立。我将从K99阶段走出来，结合工程学和神经生理学 我的两位导师都不具备的知识，让我能够脱离他们，占据一席之地 桥接技术与脑干神经生理学。使用在AIMS 1、2中开发和验证的技术 和3.2，并利用AIM 3.2的早期临床结果，我将在R00阶段提交R01赠款。 这笔拨款预计将更深入地使用镇静药物与神经成像，以探索深度的作用 支持意识的大脑核团。鉴于迫切需要更好地了解这些原子核，以及 7T MRI在实现这种理解方面的巨大潜力，我预计我将在R00中脱颖而出 在麻省理工学院或其他地方寻找竞争激烈的教职候选人。

Project Summary/Abstract: Networks of small nuclei in the meso and diencephalon (thalamus, hypothalamus, brainstem, etc.) and their connections to the cortex are critical to understanding consciousness and the onset of sedation during anesthesia. Yet despite their importance for daily survival, the functional connections among nuclei and between nuclei and cortex remain poorly understood. Ultra high field MRI at or above 7 Tesla (7T) provides several benefits for studying deep brain nuclei in humans, including improved image Signal to Noise Ratio (SNR) and improved contrast (CNR) for susceptibility based structural (SWI) and functional (BOLD) imaging as well as greater T1-dispersion. In addition to problems stemming from their small size, the study of nuclei at 7T is impeded by both static and dynamic variations in the background magnet field (B0) at these locations. These B0 variations cause image artifacts such as ghosting, signals voids, blurring, and geometric distortion. ΔB0 order and cannot compensate dynamic ΔB0. In the current project, we propose a comprehensive field Innovation: Standard B0 shim coils on commercial MRI scanners can only compensate static up to 2nd monitoring and control system to null high spatial order static and dynamic field variations at 7T. The system will use integrated RF-shim coil elements for maximum shimming and RF efficiency, NMR field probes for field monitoring, and feedback control for real-time shim updating. We are the first to combine these technologies in a unified system capable of largely overcoming the obstacle of ΔB0 in 7T MR imaging. Validation: We use the proposed system to (a.) reduce the standard deviation of B0 inhomogeneity on a slice-optimized basis over the whole brain; (b.) stabilize the phase of EPI time-series data; (c.) mitigate ghosting in multi-shot EPI; (d.) image and identify known functional networks between the brainstem and cortex in single subjects; and (e.) test a hypothesis based on animal models about the action of the anesthetic dexmedotomidine on a brainstem circuit involving three specific nuclei. Clinical benefit: By providing a new tool for studying the activity of brainstem nuclei during sedation, this project paves the way for future efforts to improve our understanding of neural circuits, develop safer site-specific anesthetic drugs, and potentially reduce post-operative delirium and cognitive impairment. Training: I am fortunate to be a part of the exceptionally rich neuroimaging environment at the MGH Martinos Center, one of the premier environments in the world for developing and validating the proposed field control technology. My K99/R00 proposal is designed to help me pivot from a MRI physicist into an independent investigator with enough background in neurobiology to ask clinically significant questions involving deep brain circuits and then develop targeted high-field MRI technology to answer them. To this end, I will require additional training, coursework, and mentorship in the K99 phase focusing on fMRI, neuroscience, physiology, and pharmacology. Structured training will include coursework, tutorials, workshops, neuroimaging seminars, and clinical exposure. The training plan includes the following: 1. Continued MR physics and hardware mentorship from Dr. Lawrence Wald 2. Training in functional MRI data acquisition and analysis, guidance by Drs. Jonathan Polimeni and Marta Bianciardi on ultra-high field fMRI data, and help from Drs. Randy Buckner and Vitaly Napadow in functional connectivity analysis. 3. Courses on neuroscience and physiology as well as guided study of brainstem nuclei and associated circuits in the arousal pathway, led by Drs. Emery Brown, Brian Edlow, and Vitaly Napadow. 4. Coursework in pharmacology and mentorship by Dr. Brown in designing and conducting anesthesia studies and understanding drug action on the brainstem in the broader context of human physiology. 5. Annual conference attendance including ISMRM and HBM. 6. Participation in the BrainMap neuroimaging seminar series and MGH Radiology Grand Rounds. 7. Career guidance from my primary mentors, including advice on grant-writing and the faculty job search. I am confident that this foundation will enable me to collaborate effectively with neuroscientists and clinicians in neuroimaging studies that depict brainstem anatomy and function in unprecedented detail. Transition to independence: My strong background in hardware and MRI physics, combined with my training and mentorship plan, will enable the success of this project and my subsequent transition to independence. I will emerge from the K99 phase with a combination of engineering and neurophysiology knowledge that neither of my mentors possesses, allowing me to separate from them and occupy a niche bridging technology and brainstem neurophysiology. Using technology developed and validated in Aims 1, 2 and 3.2, and leveraging early clinical findings of Aim 3.2, I will submit an R01 grant during the R00 phase. The grant is expected to be a more in-depth use of sedative drugs with neuroimaging to probe the role of deep brain nuclei in supporting consciousness. Given the compelling need to better understand these nuclei, and the enormous potential of 7T MRI for enabling this understanding, I anticipate that I will emerge in the R00 phase a highly competitive candidate for faculty positions either at MGH or elsewhere.