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（由应用程序提供）：拟议的研究的目的是用尖端的离体成像技术绘制人类白质（WM）的组织。这项工作将产生有关几个远程WM投影的微观级别信息，以及为前额叶皮层（PFC）提供更有针对性的电路映射。这些电路在精神科应用中特别感兴趣，但迄今为止，它们仅在非人类隐私中广泛映射。具体而言，在猕猴中使用示踪剂注射研究的最新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途径（例如c骨束（CB），calosum callosum（cc）和fasciculus（uf）（UF），以及他们的conduits。例如，UF由几个子键组成：有些遵循UF的整个轨迹，而另一些则仅用于其轨迹的部分轨迹，然后跳下并加入其他大型途径，例如CB，CC等。映射人类大脑中较大WM途径的这些独特的组成部分都在挑战InVivo和Ex Vivo和Ex Vivo。侵入性注射研究不适用于人类，常规的2D组织学技术（如髓磷脂染色）不能用于推断轴突束的3D方向。扩散MRI（DMRI）可以通过测量通过WM的水分子扩散来间接地提供这些方向的估计。但是，它容易在复杂的WM体系结构领域出现错误，并且需要通过独立的测量来源进行验证。在这项工作中，我们将结合高分辨率的高分子DMRI与极化敏感的光学相干断层扫描术（PS-OCT）（PS-OCT），在验尸后人类大脑中提取有关WM领域的微观信息，以使常规DMRI混淆常规DMRI，我们将利用MGH Connectom scanner，比8次强制启用型号的范围划定的范围，并具有8次强制性范围的范围。高SNR，高分辨率DMRI。我们将开发一个专门的接收线圈阵列，用于在连接扫描仪上进行体内人体大脑成像，这将使我们能够以前所未有的分辨率和SNR收集全脑DMRI数据。这项工作生产的金标准DMRI和PS-OCT数据将用于构建一个新型WM解剖图集，该地图将其纳入PI基于先前工作的自动化全球概率拖拉工具中。该工具将允许较小的WM捆绑包的新的，详细的分类法以及大型WM途径的经典定义，可以自动从常规质量DMRI数据中自动重建，这些数据可以在常规扫描仪上收集。拟议的工作有望促进我们对人类神经循环系统组织的理解。将人类DMRI的研究从WM途径的当前视图转移到一个束中，将多个较小的捆绑包合并在其轨迹沿不同部分的一条途径上融合；并提供使用常规神经影像数据研究此详细的WM分类法的工具。