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

使用综合磁场监测，通过 7 特斯拉 MRI 改进深部脑核的成像

• 批准号: 9981738
• 负责人: Jason P Stockmann
• 金额: $ 24.89万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9981738
• 关键词: Adrenergic Receptor; Air; Anatomy; Anesthesia procedures; Anesthetics; Animal Model; Arousal; Binding; Blood; Brain; Brain Stem; Brain imaging; Brain region; Breathing; Cell Nucleus; Chest wall structure; Clinical; Conscious; Cortical Column; Data; Data Analyses; Dexmedetomidine; Echo-Planar Imaging; Educational workshop; Electrodes; Electroencephalography; Elements; Engineering; Environment; Faculty; Feedback; Financial compensation; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Grant; Heterogeneity; Human; Hypothalamic structure; Image; Impaired cognition; Incidence; Individual; Intralaminar Nuclear Group; Knowledge; Lateral; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Mentors; Mentorship; Methods; Modality; Monitor; Morphologic artifacts; Motion; Neurobiology; Neurons; Neurosciences; Noise; Occupations; Oral cavity; Output; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Phase; Physics; Physiology; Play; Pontine structure; Positioning Attribute; Positron-Emission Tomography; Predisposition; Preoptic Areas; Radiology Specialty; Recording of previous events; Recovery; Research Personnel; Resolution; Respiration; Rest; Role; Scanning; Sedation procedure; Series; Signal Transduction; Sinus; Site; Slice; Structure; System; Technology; Testing; Thalamic structure; Time; Tissues; Training; Update; Validation; Variant; Visual Cortex; Vocational Guidance; Writing; anatomic imaging; basal forebrain; base; clinically significant; data acquisition; design; diencephalon; drug action; improved; innovation; locus ceruleus structure; lung volume; magnetic field; nervous system disorder; neural circuit; neuroimaging; neurophysiology; postoperative delirium; preservation; real time monitoring; respiratory; sedative; stem; success; symposium; tool

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.

项目概要/摘要： 中脑和间脑（丘脑、下丘脑、脑干等）小核团网络和 它们与大脑皮层的连接对于理解意识和镇静作用的发生至关重要。 麻醉然而，尽管它们对日常生存很重要，但细胞核之间的功能联系， 核与皮层之间的联系仍然知之甚少。7特斯拉（7 T）或以上的超高场MRI提供 研究人类脑深部核团的几个好处，包括改善图像信噪比 (SNR)和基于磁化率的结构（SWI）和功能（BOLD）成像的对比度（CNR）提高， 以及更大的T1分散。除了因其小尺寸而产生的问题外，在7 T下对原子核的研究 受到这些位置处背景磁场（B 0）的静态和动态变化的阻碍。 这些B 0变化导致图像伪影，例如重影、信号空洞、模糊和几何失真。 ΔB0 命令，不能补偿动态Δ B 0。在目前的项目中，我们提出了一个全面的领域， 创新：商用MRI扫描仪上的标准B 0匀场线圈只能补偿静电 到第二个 监测和控制系统，以消除7 T下的高空间阶静态和动态场变化。系统 将使用集成的RF匀场线圈元件，以实现最大匀场和RF效率， 监控和反馈控制，用于实时填隙更新。我们是第一个将这些联合收割机 在一个统一的系统中的技术，能够在很大程度上克服7 T MR成像中的Δ B 0的障碍。 验证：我们使用所提出的系统（a.）降低B 0不均匀性的标准差， 全脑上的切片优化基础;（B.）稳定EPI时间序列数据的相位;（c.）减轻 多激发EPI中的重影;（d.）成像并识别脑干和脑干之间的已知功能网络， 单个受试者的皮质;和（e.）基于动物模型检验关于麻醉剂作用的假设 右美托咪定在涉及三个特定核团的脑干回路上的作用。临床益处：通过提供新的 作为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，开发更安全的部位特异性麻醉药物， 减少术后谵妄和认知障碍。 培训：我很幸运能成为MGH异常丰富的神经成像环境的一部分 Martinos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/R 00提案旨在帮助我从MRI物理学家转变为 独立研究者，具有足够的神经生物学背景，可提出临床重要问题 涉及大脑深部回路，然后开发有针对性的高场MRI技术来回答这些问题。为此目的， 我将需要额外的培训，课程，并在K99阶段的指导，重点是功能磁共振成像， 神经科学、生理学和药理学。结构化培训将包括课程作业，辅导， 研讨会、神经影像学研讨会和临床暴露。培训计划包括以下内容： 1.劳伦斯·沃尔德博士继续提供MR物理和硬件指导 2.功能性MRI数据采集和分析培训，由Jonathan Polimeni和玛尔塔博士指导 Bianciardi对超高场fMRI数据的研究，以及Randy Buckner和Vitaly Napadow博士的帮助。 功能连接性分析 3.神经科学和生理学课程以及脑干核团和相关的指导研究 埃默里·布朗、布莱恩·埃德洛和维塔利·纳帕多博士领导的唤醒通路中的回路。 4.布朗博士在设计和进行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理解药物对脑干的作用。 5.参加ISMRM和HBM的年会。 6.参加BrainMap神经影像系列研讨会和MGH放射学大圆桌会议。 7.来自我的主要导师的职业指导，包括关于赠款写作和教师求职的建议。 我相信，这个基础将使我能够有效地与神经科学家和临床医生合作， 神经影像学研究以前所未有的细节描绘脑干解剖和功能。 过渡到独立：我在硬件和MRI物理学方面的强大背景，加上我的 培训和指导计划，将使这个项目的成功和我随后的过渡， 独立我将从K99阶段走出来，将工程学和神经生理学结合在一起， 我的两位导师都不具备的知识，让我能够与他们分开，占据一席之地。 桥接技术和脑干神经生理学。使用目标1、2中开发和验证的技术 和3.2，并利用目标3.2的早期临床发现，我将在R 00阶段提交R 01资助。 该补助金预计将是一个更深入的使用镇静药物与神经影像学，以探讨作用的深 支持意识的脑核团。鉴于迫切需要更好地了解这些核， 7 T MRI在实现这种理解方面的巨大潜力，我预计我将在R 00中出现 阶段一个非常有竞争力的候选人在MGH或其他地方的教师职位。