Unlocking whole brain, layer-specific functional connectivity with 3D VAPER fMRI

摘要 超高场扫描仪可用性的提高为在亚毫米范围内进行功能磁共振成像提供了机会 空间尺度，并能够在体内探测人脑的层流功能。在这个新的调查 神经科学中的介观空间尺度不仅促进了我们对大脑皮质微循环的理解 活体在健康和疾病中的作用，但也有助于弥合宏观(如常规功能磁共振成像、行为)之间的差距 以及大脑功能的微观(例如，细胞外记录)测量。然而，尽管有希望， 尽管有潜力，但在这一规模上实现足够的敏感性、特异性、准确性和覆盖面仍然存在关键障碍。 直到最近，大多数层-功能磁共振研究都局限于使用任务设计的初级皮质之一。 脑部覆盖率较小且大血管污染的序列对比 根据失真不匹配的解剖参考粗略地测量和定义皮质层。 在这个项目提案中，我们将开发一个全脑层特定的人类成像序列工具，用于 实现高分辨率(GB 800微米各向同性)、高特异性(与非特异性无空间偏差)的功能磁共振成像 静脉信号(粗体)、高灵敏度(在层级分辨率下的稳健测量)、高空间精度 (在原生fMRI空间进行分层fMRI分析，以避免配准造成的模糊和错误)，全脑 覆盖范围，并最终将层功能磁共振扩展到更灵活的基于连接的实验设计。我们会 采用两种序贯方法，一种是血容量和灌注量综合(VAPER)造影法 提高层fMRI的特异性，另一个是磁化转移(MT)加权解剖EPI成像 便于在自然功能磁共振成像空间中确定皮质深度的技术。我们将改进脉冲设计 VAPER/MT准备，并将其与跳过的CAIPI 3D-EPI(分段采集，带 Caipirinha采样)采集，作为一种新的采集方法，我们称之为VAPER/MT-3D-EPI。我们将开发 全脑0.8 mm各向同性成像序列及优化设计 通过测量依赖于层的活性来提高特异性。我们将使用这个新的序列来收集完整的- 人类在静息状态和看电影期间的亚毫米脑功能图像数据集， 建立特定于层的功能连通性分析管道，并调查不同 大脑皮层在维持大脑网络中的作用。我们将公开分享数据和分析代码给 促进Layer fMRI方法的开发，并将VAPER/MT-3D-EPI演示为用户友好的Layer FMRI 网络神经科学的工具。

ABSTRACT The increased availability of ultra-high field scanners provides an opportunity to perform fMRI at sub-millimeter spatial scales and enables in vivo probing of laminar function in the human brain. Investigations at this new mesoscopic spatial scale in neuroscience not only advance our understanding of the cortical micro-circuitry in vivo in health and disease, but also help bridge the gap between macroscopic (e.g., conventional fMRI, behavior) and microscopic (e.g., extracellular recordings) measures of brain function. However, despite promising potentials, critical barriers remain in achieving adequate sensitivity, specificity, accuracy, coverage at this scale. Until recently, most layer-fMRI studies have been confined to one of the primary cortices using a task design with a small brain coverage together with macro-vascular-contaminated sequence contrasts for functional measurement and defining cortical layers roughly based on distortion mis-matched anatomical reference. In this project proposal, we will develop a whole-brain layer-specific imaging sequence tool in humans, for achieving fMRI at high resolution (£800 µm isotropic), high specificity (not being spatially biased with unspecific vein signals as in BOLD), high sensitivity (robust measurement at layer-level resolution), high spatial accuracy (layer fMRI analysis in native fMRI space to avoid blurring and errors arising from registration), whole brain coverage, and eventually extending layer fMRI to more flexible connectivity-based experiment designs. We will adapt two sequence methods, one is an integrated blood volume and perfusion (VAPER) contrast method to improve layer fMRI specificity, and the other is a magnetization transfer (MT) weighted anatomical EPI imaging technique to facilitate determination of cortical depth in native fMRI space. We will improve the pulse design of the VAPER/MT preparation and incorporate them with a skipped-CAIPI 3D-EPI (segmented acquisition with CAIPIRINHA sampling) acquisition, as a new method we will call VAPER/MT-3D-EPI. We will develop the sequence and optimize its design for a whole-brain 0.8-mm isotropic imaging, and demonstrate its sensitivity and specificity through measuring layer-dependent activity. We will use this new sequence to collect a whole- brain submillimeter functional image dataset in humans at both resting state and during movie-watching, establish the layer-specific functional connectivity analysis pipeline, and investigate the involvement of different cortical layers in the maintenance of the brain networks. We will publicly share the data and analysis code to facilitate development of layer fMRI methods and demonstrate VAPER/MT-3D-EPI as a user-friendly layer fMRI tool for network neuroscience.