Accessing the Neuronal Scale: Designing the Next Generation of Compact Ultra High Field MRI Technology for Order-of-Magnitude Sensitivity Increase in Non-Invasive Human Brain Mapping

项目摘要 对正常大脑功能和神经系统疾病/精神疾病的全面了解将 需要破译行为和认知背后的复杂大脑网络，无论是在全脑还是全脑， 和微观尺度。在结构和功能上绘制这些大脑网络的难度在于， 人类受试者具有足够的灵敏度和分辨率，以了解正常功能并检测病理性 变革是一项根本性挑战。认识到这些挑战，NIH和其他资金 几十年来，各机构一直在支持脑图谱的新举措，从“脑十年”开始， 接着是大脑的十年后的十年，大脑的新世纪，人类连接体 项目，以及最近的大脑倡议。大多数这些大脑映射计划都以MRI为特色， 研究完整的活人脑的首要工具，非侵入性，高分辨率，高分辨率， 对许多微妙的生理和病理过程敏感。例如，NIH资助的人类 连接组项目（HCP）于2009年启动，旨在全面绘制1，200名健康人的大脑回路。 研究人员使用MRI，并已经对神经科学领域产生了很大的影响。HCP使用扩散 MRI（dMRI）和基于BOLD的功能性MRI（fMRI），以获得全脑结构和功能连接 1.25- 2 mm分辨率（2-8µL体素）下的个体受试者图。这种粗糙的分辨率导致 在105-106个神经元上的单体素响应的空间模糊。美国国立卫生研究院大脑倡议呼吁破坏性的 新的方法来解决大脑电路连接和功能在显着更高的时空和 微观结构分辨率这个为期2年的概念验证BRAIN R 01将专注于生产一个完整的， 经过验证的设计，适用于下一代紧凑型、低成本、高性能超高场（UHF）MRI 系统，能够在104个神经元（~0.2μL）的规模上解析神经连接和电路， 非侵入性地取出整个人脑这将解决BRAIN 2025中确定的特定目标， 这就要求在针对具有体素体积的全脑研究的MR方法学方面取得重大进展 短期内为0.3-0.4微升，长期为0.1微升或更好。我们在这个项目中的具体目标是重新- 设计UHF MRI系统的所有前端硬件组件，从而解决技术和 这些物理挑战严重阻碍了这种人脑成像模式。我们将开发 几项颠覆性技术，旨在协同创造一个大大降低成本，但更高的 执行超高频MRI系统：1）超紧凑超高频磁体技术; 2）超高性能梯度 硬件;以及3）创新的垫片和RF阵列技术，旨在完全校正主磁场和RF 不均匀性问题。我们的工作的实际影响将是使人类大脑得到极大的改善 使用dMRI和fMRI进行映射，同时解决主要的技术和成本限制， 超高频核磁共振。

Project Summary A complete understanding of both normal brain function and neurological disorders / mental illness will require the deciphering of the complex brain networks that underlie behavior and cognition, at both whole-brain and microscopic scales. The difficulty of structurally and functionally mapping these brain networks in living human subjects with sufficient sensitivity and resolution to understand normal function and detect pathological change represents a fundamental challenge. Recognizing these challenges, the NIH and other funding agencies have supported new initiatives in brain mapping for decades, starting with the Decade of the Brain, followed by the Decade after the Decade of the Brain, the New Century of the Brain, the Human Connectome Project, and most recently the BRAIN Initiative. Most of these brain mapping initiatives have featured MRI, the premier tool for studying the intact living human brain, non-invasively, at high resolution, and with high sensitivity to many subtle physiological and pathological processes. For example, the NIH-funded Human Connectome Project (HCP) was launched in 2009 to comprehensively map brain circuitry in 1,200 healthy subjects using MRI, and has already had a large impact on the neuroscience field. The HCP uses diffusion MRI (dMRI) and BOLD-based functional MRI (fMRI) to derive whole-brain structural and functional connectivity maps for individual subjects at 1.25-2mm resolution (2-8µL voxels). Such coarse resolution results in the spatial blurring of single-voxel responses over 105-106 neurons. The NIH BRAIN Initiative calls for disruptive new approaches to resolving brain circuit connections and function at dramatically higher spatiotemporal and microstructure resolution. This 2-year proof-of-concept BRAIN R01 will focus on producing a complete and validated design for a next-generation, compact, low-cost, high-performance ultra-high-field (UHF) MRI system, capable of resolving neural connections and circuitry at the scale of 104 neurons (~0.2µL), throughout the entire living human brain non-invasively. This would address a specific target identified in BRAIN 2025, which calls for significant developments in MR methodology targeting whole brain studies with voxel volumes of 0.3-0.4µL in the short term, and 0.1µL or better in the long term. Our specific goals in this project are to re- engineer all front-end hardware components of the UHF MRI system, thereby resolving the technological and physics challenges that have been severely holding back this human brain imaging modality. We will develop several disruptive technologies, designed synergistically to create a dramatically lower cost but higher performing UHF MRI system: 1) ultra-compact UHF magnet technology; 2) ultra-high-performance gradient hardware; and 3) innovative shim and RF array technologies designed to fully correct both main field and RF inhomogeneity problems. The practical impact of our work will be to enable greatly improved human brain mapping using dMRI and fMRI, while simultaneously solving the major technological and cost limitations of UHF MRI.