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.

项目摘要/摘要： 中脑和间脑（丘脑、下丘脑、脑干等）中的小核网络 它们与皮质的联系对于理解意识和镇静作用的发生至关重要 然而，尽管它们对于日常生存很重要，但细胞核和神经元之间的功能联系。 对于 7 特斯拉 (7T) 或以上的超高场 MRI 所提供的细胞核和皮质之间的关系仍知之甚少。 研究人类深部脑核的几个好处，包括提高图像信噪比 基于磁敏度的结构 (SWI) 和功能 (BOLD) 成像的 (SNR) 和改进的对比度 (CNR) 以及更大的 T1 色散 除了尺寸小带来的问题外，对 7T 原子核的研究也存在问题。 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，例如重影、信号空白、模糊和几何失真。 ΔB0 在当前项目中，我们提出了一个综合领域。 创新：商用 MRI 扫描仪上的标准 B0 匀场线圈只能补偿静电 最多第二名 监测和控制系统可消除 7T 的高空间阶静态和动态场变化。 将使用集成射频匀场线圈元件来实现最大匀场和射频效率，核磁共振场探头用于现场 我们是第一个将这些功能结合起来的公司。 统一系统中的技术能够很大程度上克服7T MR成像中ΔB0的障碍。 验证：我们使用所提出的系统来 (a.) 减少 B0 不均匀性的标准偏差 对整个大脑进行切片优化；(b.) 稳定 EPI 时间序列数据的相位；(c.) 减轻 多镜头 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；以及（e.）测试基于动物模型的关于麻醉作用的假设 右美托咪定对脑干回路三个特定核团的临床益处：通过提供新的参与。 作为研究镇静期间脑干核活动的工具，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，开发更安全的特定部位麻醉药物，并有可能 减少术后谵妄和认知障碍。 培训：我很幸运能够成为麻省总医院极其丰富的神经影像环境的一部分 马蒂诺斯中心，世界上开发和验证拟议领域的首要环境之一 我的 K99/R00 提案旨在帮助我从 MRI 物理学家转变为一名 MRI 物理学家。 具有足够神经生物学背景的独立调查员，可以提出临床重要问题 涉及深部脑回路，然后开发有针对性的高场磁共振技术来回答它们。 我将在 K99 阶段需要额外的培训、课程和指导，重点关注 fMRI、 神经科学、生理学和药理学的结构化培训将包括课程作业、教程、 研讨会、神经影像研讨会和临床接触培训计划包括以下内容： 1. Lawrence Wald 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 Marta 博士指导 Bianciardi 的超高场功能磁共振成像数据，以及兰迪·巴克纳 (Randy Buckner) 和维塔利·纳帕多 (Vitaly Napadow) 博士的帮助。 功能连接分析。 3. 神经科学和生理学课程以及脑干核团及其相关的指导研究 唤醒通路中的电路，由 Emery Brown、Brian Edlow 和 Vitaly Napadow 博士领导。 4. 药理学课程以及布朗博士设计和进行麻醉研究的指导 并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ISMRM和HBM等年度会议。 6. 参加 BrainMap 神经影像研讨会系列和 MGH 放射科大查房。 7. 我的主要导师的职业指导，包括有关资助写作和教师求职的建议。 我相信这个基金会将使我能够与神经科学家和反叛者有效合作 神经影像研究以前所未有的细节描述脑干解剖结构和功能。 过渡到独立：我在硬件和 MRI 物理学方面的深厚背景，结合我的经验 培训和指导计划，将使这个项目取得成功，并让我随后过渡到 我将通过工程学和神经生理学的结合从 K99 阶段中脱颖而出。 我的导师都不具备的知识，让我能够与他们分开并占据一席之地 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 R00 阶段提交 R01 资助。 该资助预计将更深入地使用镇静药物与神经影像学来探讨深部神经影像的作用 考虑到更好地理解这些神经核的迫切需要，以及 7T MRI 在实现这种理解方面的巨大潜力，我预计我将出现在 R00 中 为麻省总医院或其他地方的教职职位挑选一位极具竞争力的候选人。