Connectome 2.0: Developing the next generation human MRI scanner for bridging studies of the micro-, meso- and macro-connectome

Connectome 2.0：开发下一代人体 MRI 扫描仪，用于桥接微观、中观和宏观连接组研究

• 批准号: 9789878
• 负责人: PETER J. BASSER
• 金额: $ 297.47万
• 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: 2018-09-21 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789878
• 关键词: Address; Adult; Anatomy; Axon; Behavior; Biological; Brain; Brain imaging; Brain region; Calibration; Cell Density; Cellular Structures; Cognition; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Electron Microscopy; Elements; Engineering; Generations; Goals; Gold; Heterogeneity; Human; Hybrids; Image; Individual; Length; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Microscope; Microscopic; Morphologic artifacts; Morphology; Neuronal Plasticity; Neurons; Pathology; Performance; Physiologic pulse; Research; Resolution; Sampling; Signal Transduction; Site; Structure; System; Technology; Time; Tissues; Translating; Validation; Variant; Work; biophysical model; brain tissue; connectome; design; experience; functional plasticity; gray matter; human imaging; improved; in vivo; instrument; microCT; microscopic imaging; neural circuit; next generation; relating to nervous system; technology development; technology validation; tool; tractography; validation studies; white matter

SUMMARY We present Connectome 2.0, the next-generation human MRI scanner for imaging structural anatomy and connectivity spanning the microscopic, mesoscopic and macroscopic scales. This work builds upon our expertise in engineering the first human Connectome MRI scanner with 300 mT/m maximum gradient strength (Gmax), the highest ever achieved for a human system, for the Human Connectome Project (HCP). The goal of the HCP was to map the macroscopic structural connections of the in vivo healthy adult human brain using diffusion tractography. While this instrument has made important contributions to our understanding of macroscale connectional topology, our experience with the scanner over the last seven years has taught us that dedicated high-gradient performance scanners can also acquire a rich array of diffusion measurements that provide unparalleled in vivo assessment of neural tissue microstructure, such as the relative size and packing density of cells and axons. However, the current Connectome instrument is limited in its ability to resolve the full range of length scales needed to probe the microscopic and mesoscopic structure of the brain, due to basic design limitations, important technical elements, and biological interactions with the large rapidly switching gradients. Our experience with the first generation Connectome scanner and realization of its limitations motivates our multi-site proposal for the next generation human Connectome MRI scanner (Connectome 2.0) to achieve sensitivity to a broader range of cellular and axonal size scales, morphologies, and interconnections represented throughout the brain. Our goal here is to translate our initial experience into building a one-of-a-kind high-slew rate, ultra- high-gradient strength MRI scanner that is optimized for the study of neural tissue microstructure and neural circuits across multiple length scales. In order to maximize the resolution of this in vivo microscope for studies of the living human brain, we will push the diffusion resolution limit to unprecedented levels by (1) nearly doubling the current Gmax to 500 mT/m and tripling the maximum slew rate to 600 T/m/s; (2) pushing the limits of the RF receive coils and gradient characterization to enable maximum sensitivity with greatly reduced artifacts using real-time eddy current corrected dMRI acquisitions; (3) developing new pulse sequences to achieve the highest diffusion- and spatial-resolution ever achieved in vivo; and (4) calibrating the measurements obtained from this next generation instrument through systematic validation of the diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales. We envision creating the ultimate diffusion MRI machine capable of addressing the BRAIN 2025 mandate to image across scales, from the microscopic scale needed to probe cellular heterogeneity and plasticity, to the mesoscopic scale for enumerating the distinctions in cortical structure and connectivity that define cyto- and myeloarchitechtonic boundaries, to improvements in estimates of macroscopic connectivity.

概括 我们提出Connectome 2.0，这是用于成像结构解剖结构和的下一代人MRI扫描仪 跨越显微镜，介观和宏观尺度的连通性。这项工作以我们的专业知识为基础 在工程中，第一个具有300吨/m最大梯度强度（GMAX）的人连接组MRI扫描仪， 人类系统（HCP）的人类系统有史以来最高的成就。 HCP的目标是 绘制使用扩散的体内健康成人人脑的宏观结构连接 拖拉机。尽管该工具为我们对宏观的理解做出了重要贡献 连接拓扑，我们在过去七年中与扫描仪的经验告诉我们， 高梯度性能扫描仪还可以获取丰富的扩散测量值 神经组织微观结构的体内评估无与伦比，例如相对大小和填料密度 细胞和轴突。但是，当前的Connectome仪器在解决全部范围的能力方面受到限制 由于基本设计，探测大脑的显微镜和介绍性结构所需的长度尺度 局限性，重要的技术要素以及与大型快速切换梯度的生物相互作用。 我们在第一代Connectome扫描仪和实现局限性的经验激发了我们的促进 下一代人Connectome MRI扫描仪（Connectome 2.0）的多站点建议 对代表的细胞和轴突尺寸尺度，形态和互连的敏感性 整个大脑。 我们的目标是将我们的最初经验转化为建立一种独一无二的高级速率，超级 - 高梯度强度MRI扫描仪，可用于研究神经组织微观结构和神经 跨多个长度尺度的电路。为了最大化该体内显微镜的分辨率 在活着的人大脑中，我们将将扩散分辨率限制推向前所未有的水平（1） 将当前的Gmax加倍，达到500 mt/m，并将最大振荡速率提高到600 t/m/s； （2）推动极限 RF接收线圈和梯度表征以极大的降低，以实现最大的灵敏度 使用实时涡流校正的DMRI采集的伪像； （3）将新的脉冲序列开发到 实现在体内实现的最高扩散和空间分辨率； （4）校准 通过系统验证扩散从该下一代工具获得的测量 高保真幻像和离体脑组织的微观结构指标在逐渐更细的尺度上。我们 设想创建最终扩散的MRI机器，能够解决大脑2025的授权以形象 跨量表，从探测细胞异质性和可塑性所需的微观量表到 介质量表，用于列举定义细胞和连通性的区别和连通性的区别 骨髓技术边界，以改善宏观连通性的估计。