Multimodal mapping of the neurocircuitry of the human prefrontal cortex

人类前额皮质神经回路的多模态映射

• 批准号: 9122980
• 负责人: Anastasia Yendiki
• 金额: $ 57.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9122980
• 关键词: Algorithms; Anatomy; Architecture; Area; Atlases; Autistic Disorder; Axon; Brain; Complex; Corpus Callosum; Custom; Data; Destinations; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Fiber; Gold; Histological Techniques; Human; Image; Image Analysis; Imaging Techniques; Imaging technology; Individual; Injection of therapeutic agent; Macaca; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mental disorders; Methods; Microscopic; Modeling; Monkeys; Myelin; Optical Coherence Tomography; Pathway interactions; Prefrontal Cortex; Probability; Protocols documentation; Research; Research Personnel; Resolution; Scanning; Shapes; Software Tools; Source; Staining method; Stains; Structure; System; Taxonomy; Techniques; Temporal Lobe; Time; Tracer; Uncertainty; Validation; Vertebral column; Work; base; bioimaging; brain circuitry; brain tissue; clinically relevant; connectome; design; improved; in vivo; instrument; instrumentation; interest; model building; neuroimaging; nonhuman primate; novel; optical imaging; public health relevance; reconstruction; tool; water diffusion; white matter

 DESCRIPTION (provided by applicant): The objective of the proposed research is to map the organization of human white matter (WM) with cutting-edge ex vivo imaging technologies. This work will produce microscopic-level information on several long-range WM projections, as well as a more targeted mapping of circuits that serve the prefrontal cortex (PFC). These circuits are of particular interest in psychiatric applications but they have been heretofore mapped extensively only in non-human primates. Specifically, recent work with tracer injection studies in macaque monkeys has established how small fiber bundles that originate in different areas of the PFC reach their destinations by using the large WM pathways, such as the cingulum bundle (CB), corpus callosum (CC) and uncinate fasciculus (UF), as their conduits. For example, the UF is composed of several sub-bundles: some that follow the entire trajectory of the UF and others that join the UF only for part of its trajectory to then jump off and join other large pathways, like the CB, CC, etc. Mapping these distinct components of larger WM pathways in the human brain is challenging both in vivo and ex vivo. Invasive injection studies are not applicable to humans and conventional 2D histological techniques like myelin staining cannot be used to infer the 3D orientation of axon bundles. Diffusion MRI (dMRI) can provide estimates of these orientations indirectly, by measuring the diffusion of water molecules through the WM. However, it is prone to errors in areas of complex WM architecture and requires validation by an independent source of measurements. In this work we will combine high-resolution, high-SNR ex vivo dMRI with polarization-sensitive optical coherence tomography (PS-OCT) in post mortem human brains to extract microscopic information on WM areas that confound conventional dMRI, and to perform a detailed mapping of the projections of the PFC. We will take advantage of the MGH Connectom scanner, a unique instrument that can achieve 8 times stronger diffusion-encoding gradients than routine scanners, and was designed specifically for high-SNR, high-resolution dMRI. We will develop a specialized receive coil array for imaging ex vivo human brains on the Connectom scanner, which will allow us to collect whole-brain dMRI data with unprecedented resolution and SNR. The gold-standard dMRI and PS-OCT data produced by this work will be used to construct a novel atlas of WM anatomy, which will be incorporated in a tool for automated global probabilistic tractography, building on prior work by the PI. This tool will allow both the new, detailed taxonomy of smaller WM bundles, as well as the classical definitions of large WM pathways, to be reconstructed automatically from routine-quality in vivo dMRI data that can be collected on conventional scanners. The proposed work promises to advance our understanding of the organization of human neurocircuitry; to move human dMRI studies from the current view of a WM pathway as a single bundle to one where multiple smaller bundles merge on and off a pathway at different parts along its trajectory; and to provide the tools for studying this detailed WM taxonomy using routine neuroimaging data.

 描述（由申请人提供）：拟议研究的目的是利用尖端的离体成像技术绘制人类白质（WM）的组织图。这项工作将产生有关多个远程 WM 预测的微观信息，以及服务于前额皮质 (PFC) 的电路的更有针对性的映射。这些回路在精神病学应用中特别令人感兴趣，但迄今为止仅在非人类灵长类动物中广泛绘制了它们的图谱。具体来说，最近在猕猴身上进行的示踪剂注射研究已经确定了源自 PFC 不同区域的小纤维束如何通过使用大的 WM 通路（例如扣带束 (CB)、胼胝体 (CC) 和钩束 (UF)）作为管道到达目的地。例如，UF 由几个子束组成：一些子束遵循 UF 的整个轨迹，而另一些子束仅在其轨迹的一部分中加入 UF，然后跳出并加入其他大型通路，如 CB、CC 等。在人脑中绘制更大 WM 通路的这些不同组成部分在体内和体外都具有挑战性。侵入性注射研究不适用于人类，并且髓磷脂染色等传统的 2D 组织学技术不能用于推断轴突束的 3D 方向。扩散 MRI (dMRI) 可以通过测量水分子通过 WM 的扩散来间接估计这些方向。然而，它在复杂的 WM 架构领域很容易出现错误，并且需要由独立的测量源进行验证。在这项工作中，我们将在死后人脑中将高分辨率、高信噪比的离体 dMRI 与偏振敏感光学相干断层扫描 (PS-OCT) 结合起来，提取与传统 dMRI 相混淆的 WM 区域的微观信息，并对 PFC 的投影进行详细的映射。我们将利用 MGH Connectom 扫描仪，这是一种独特的仪器，可以实现比常规扫描仪强 8 倍的扩散编码梯度，并且专为高 SNR、高分辨率 dMRI 设计。我们将开发一种专门的接收线圈阵列，用于在 Connectom 扫描仪上对人脑进行离体成像，这将使我们能够以前所未有的分辨率和信噪比收集全脑 dMRI 数据。这项工作产生的黄金标准 dMRI 和 PS-OCT 数据将用于构建新的 WM 解剖图集，该图集将纳入自动全局概率纤维束成像工具中，以 PI 之前的工作为基础。该工具将允许根据常规扫描仪收集的常规质量体内 dMRI 数据自动重建较小 WM 束的新的详细分类法以及大型 WM 通路的经典定义。拟议的工作有望增进我们对人类神经回路组织的理解；将人类 dMRI 研究从当前将 WM 通路视为单个束的观点转变为多个较小束沿其轨迹在不同部分上下合并的观点；并提供使用常规神经影像数据研究这种详细的 WM 分类的工具。