An acquisition and reconstruction framework to enable mesoscale human fMRI on clinical 3 Tesla scanners

项目总结/摘要 功能磁共振成像（fMRI）是最广泛使用的工具，以非侵入性地测量大脑功能，并已产生 我们目前对人脑功能组织的大部分认识。然而，所有的功能磁共振成像方法 通过跟踪血流量、血容量和血流量的相关局部变化来间接测量神经元活动。 氧合，这限制了它们对潜在神经元活动的时空特异性。虽然这往往是 作为fMRI的基本限制，最近在动物模型中的光学成像研究表明， 微血管直径变化和神经活动之间的耦合。这些数据表明，人类功能磁共振成像- 就像今天所做的那样，有着巨大的未开发的潜力，只有我们能够进行测量， 只对这些最小血管的变化敏感。最近的人体研究表明， 基于对微血管直径高度敏感的脑血容量（CBV）变化跟踪的fMRI 与传统的血氧水平相比，这些变化确实提供了改善的神经特异性， 依赖（BOLD）方法。自fMRI出现以来，BOLD一直是最常用的fMRI对比剂，因为它 鲁棒性和高灵敏度，但共识是CBV提供了更忠实的测量， 神经活动由于灵敏度低，这种功能强大的非BOLD fMRI方法一直缺乏采用。 为了解决这个问题，我们将开发新的成像方法，以显着提高基于CBV的功能磁共振成像的灵敏度。 我们的方法的关键是认识到，现在有了先进的采集方法， 我们最近开发了一种方法，将功能磁共振成像中的“对比度编码”与图像编码分开。因为 在fMRI中用EPI进行的标准图像编码固有地引入了T2* 加权（并因此引入了BOLD对比度）， 新兴的非BOLD技术必须低效地为每个测量获取两组数据，以消除 后处理中不必要的BOLD污染。需要采集两组图像，沿着 必要的后处理，加上T2* 信号损失联合收割机，导致高达4倍的SNR效率损失。我们的方法， 基于我们的无失真和无模糊回波平面时间分辨成像（EPTI）技术， 通过消除不需要的BOLD加权来减少SNR损失。我们称我们的新框架为“Mz功能磁共振成像”，因为它提供了 一种纯粹基于纵向磁化（Mz）产生fMRI对比度的方法，适用于各种非磁共振成像， 功能磁共振成像方法。我们将通过将EPTI与 “VASO”创建一个有效的CBV-fMRI没有失真，模糊，或需要BOLD删除。 我们的模拟表明，我们的方法将为亚毫米CBV-fMRI提供足够的灵敏度， 3 T，并且在7 T下比现有的CBV方法性能更好;这些强大的方法在3 T下的可用性将 开放非BOLD功能磁共振成像到整个功能磁共振成像社区，提高神经元特异性，并使广泛的 中尺度fMRI的应用-例如皮质柱和层以及小皮质下核的研究- 从而为绘制全脑回路开辟了新的可能性。

PROJECT SUMMARY/ABSTRACT Functional MRI (fMRI) is the most widely-used tool to noninvasively measure brain function and has produced much of our current knowledge about the functional organization of the human brain. However, all fMRI methods measure neuronal activity indirectly by tracking the associated local changes in blood flow, volume and oxygenation, which limit their spatiotemporal specificity to the underlying neuronal activity. While this is often viewed as the fundamental limitation of fMRI, recent optical imaging studies in animal models have shown a tight coupling between microvascular diameter changes and neural activity. These data indicate that human fMRI— as it is performed today—has vast untapped potential that can only be reaped if our measurements can be made sensitive exclusively to changes in these smallest blood vessels. Recent human studies have demonstrated that fMRI based on tracking changes in cerebral blood volume (CBV) with high sensitivity to microvascular diameter changes indeed provide improved neural specificity compared to the conventional blood-oxygenation-level- dependent (BOLD) method. Since the advent of fMRI, BOLD has been the most used fMRI contrast due to its robustness and high sensitivity, yet consensus is building that CBV provides far more faithful measurements of neural activity. Adoption of this powerful non-BOLD fMRI approach has been lacking due to its low sensitivity. To address this, we will develop new imaging methods to dramatically increase sensitivity of CBV-based fMRI. The key to our approach is the recognition that it is now possible, with advanced acquisition methods that we have recently developed, to separate “contrast encoding” in fMRI from image encoding. Because the standard image encoding with EPI in fMRI inherently introduces T2* weighting (and thus BOLD contrast), emerging non-BOLD techniques must inefficiently acquire two sets of data for every measurement to remove the unwanted BOLD contamination in post-processing. The need to acquire two sets of images, along with the necessary post-processing, plus the T2* signal loss combine to cause up to 4× SNR-efficiency loss. Our method, based on our distortion- and blurring-free Echo-Planar Time-resolved Imaging (EPTI) technology, overcomes this SNR loss by eliminating the unwanted BOLD weighting. We call our new framework “Mz fMRI” as it provides a means to generate fMRI contrast based purely on longitudinal magnetization (Mz), applicable to various non- BOLD fMRI methods. We will provide a proof of concept of this powerful framework by integrating EPTI with “VASO” to create an efficient CBV-fMRI without distortion, blurring, or the need for BOLD removal. Our simulations indicate that our approach will deliver sufficient sensitivity for sub-millimeter CBV-fMRI at 3T, and will perform better than existing CBV methods at 7T; the availability of these powerful methods at 3T will open non-BOLD fMRI up to the entire fMRI community, boosting neuronal specificity and enabling broad application of mesoscale fMRI—such as studies of cortical columns and layers and small subcortical nuclei— and thereby opening new possibilities for mapping whole-brain circuitry.