The first phase of the Human Connectome Project pioneered advances in MRI technology for mapping the macroscopic structural connections of the living human brain through the engineering of a whole-body human MRI scanner equipped with maximum gradient strength of 300 mT/m, the highest ever achieved for human imaging. While this instrument has made important contributions to the understanding of macroscale connectional topology, it has also demonstrated the potential of dedicated high-gradient performance scanners to provide unparalleled in vivo assessment of neural tissue microstructure. Building on the initial groundwork laid by the original Connectome scanner, we have now embarked on an international, multi-site effort to build the next-generation human 3T Connectome scanner (Connectome 2.0) optimized for the study of neural tissue microstructure and connectional anatomy 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 maximum gradient strength from 300 mT/m to 500 mT/m and tripling the maximum slew rate from 200 T/m/s to 600 T/m/s through the design of a one-of-a-kind head gradient coil optimized to minimize peripheral nerve stimulation; (2) developing high-sensitivity multi-channel radiofrequency receive coils for in vivo and ex vivo human brain imaging; (3) incorporating dynamic field monitoring to minimize image distortions and artifacts; (4) developing new pulse sequences to integrate the strongest diffusion-encoding and highest spatial-resolution ever achieved in the living human brain; and (5) calibrating the measurements obtained from this next-generation instrument through systematic validation of diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales with accompanying diffusion simulations in histology-based micro-geometries. We envision creating the ultimate diffusion MRI instrument capable of capturing the complex multi-scale organization of the living human brain – from the microscopic scale needed to probe cellular geometry, heterogeneity and plasticity, to the mesoscopic scale for quantifying the distinctions in cortical structure and connectivity that define cyto- and myeloarchitectonic boundaries, to improvements in estimates of macroscopic connectivity.

人类连接组项目的第一阶段开创了 MRI 技术的进步，通过配备最大梯度强度 300 mT/m（有史以来最高的梯度强度）的全身人体 MRI 扫描仪来绘制活人大脑的宏观结构连接图用于人体成像。虽然该仪器为理解宏观连接拓扑做出了重要贡献，但它也证明了专用高梯度性能扫描仪在提供无与伦比的神经组织微观结构体内评估方面的潜力。在最初的 Connectome 扫描仪奠定的初步基础上，我们现已开始开展一项国际性、多站点的工作，以构建下一代人体 3T Connectome 扫描仪 (Connectome 2.0)，该扫描仪针对神经组织微观结构和连接解剖学的研究进行了优化多个长度尺度。 为了最大限度地提高用于活人大脑研究的活体显微镜的分辨率，我们将通过以下方式将扩散分辨率极限推向前所未有的水平：(1) 将当前最大梯度强度从 300 mT/m 提高到 500 mT/m 近一倍通过设计一种独一无二的头部梯度线圈，将最大转换速率从 200 T/m/s 提高到 600 T/m/s，该线圈经过优化以最大限度地减少周围神经刺激； （2）开发用于体内和离体人脑成像的高灵敏度多通道射频接收线圈； (3) 结合动态场监测以最大限度地减少图像失真和伪影； (4) 开发新的脉冲序列，以整合人类大脑中有史以来最强的扩散编码和最高的空间分辨率； (5) 通过系统验证高保真模型和离体脑组织中的扩散微观结构指标，以逐渐更精细的尺度，并伴随基于组织学的微观几何形状的扩散模拟，校准从下一代仪器获得的测量结果。我们设想创建终极扩散 MRI 仪器，能够捕获活人大脑复杂的多尺度组织——从探测细胞几何形状、异质性和可塑性所需的微观尺度，到量化皮质结构和连接性差异所需的介观尺度定义细胞和骨髓结构边界，以改善宏观连接的估计。