Understanding evoked and resting-state fMRI through multi scale imaging

通过多尺度成像了解诱发和静息态 fMRI

• 批准号: 9763653
• 负责人: R Todd Constable
• 金额: $ 103.31万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9763653
• 关键词: Animal Experiments; Animal Model; Animals; Area; Bioinformatics; Biological; Biomedical Engineering; Blood flow; Brain; Brain imaging; Cells; Communication; Complement; Data; Data Analyses; Data Set; Development; Dimensions; Disease; Disease model; Ensure; Equilibrium; Fingers; Fluorescence; Functional Magnetic Resonance Imaging; Gold; Human; Image; Imaging Device; Imaging Techniques; Interruption; Knock-out; Label; Lesion; Link; Measures; Mental Depression; Metabolic; Methodology; Methods; Microscopic; Modality; Modeling; Molecular Biology; Motor; Mus; Names; Nature; Neuroglia; Neurological Models; Neurons; Pharmacology; Physiological; Population; Post-Traumatic Stress Disorders; Property; Resolution; Rest; Rodent; Role; Scientist; Sensory; Signal Transduction; Source; System; Techniques; Testing; Therapeutic Intervention; Time; Transgenic Mice; Vibrissae; Work; animal data; autism spectrum disorder; base; blood oxygen level dependent; calcium indicator; cell type; cellular imaging; cognitive task; control theory; data modeling; design; designer receptors exclusively activated by designer drugs; excitatory neuron; experimental study; genetic manipulation; graph theory; human data; human imaging; human model; human subject; improved; inhibitory neuron; insight; mouse model; multidisciplinary; network models; neurophysiology; novel; novel strategies; optogenetics; predictive modeling; predictive test; relating to nervous system; response; spatiotemporal; temporal measurement; theories; two-photon

Project Summary This RFA is aimed at bringing together interdisciplinary teams to focus on novel, transformative and integrative efforts that will revolutionize our understanding of the biological and bioinformatics content of the data collected from non-invasive human functional brain imaging techniques. Our proposal does exactly this. We are a multidisciplinary team of scientists with combined expertise in optogenetics, two photon Ca2+ imaging, biomedical engineering, molecular biology, animal and human fMRI, network theory, data analysis and modeling. In this work, we will use a novel imaging device that combines mesoscopic imaging of genetically encoded Ca2+ indicators with very high (50m) spatial and high temporal (25ms) resolution across the entire cortex and simultaneous fMRI in transgenic mouse models. These animal experiments are designed to complement similar experiments in healthy human subjects. The results from the animal experiments will answer several long-standing questions about the source of the fMRI signal. Specifically, using imaging, we will quantify the contributions of different cell populations (excitatory neurons, inhibitory neurons, and glial cells) to the fMRI signal observed. We will be able to test and validate, for the first time, the application of graph theory approaches to the analysis of human fMRI data, and we will develop and test a new approach based on control theory for extracting more information from the fMRI signal. A powerful set of carefully controlled imaging experiments in mice will inform several aspects of analysis of human data. The human data will contain a test/retest component to ensure replication of the results and to allow predictive models to be built in one data set and tested in another. This work truly bridges scale and modalities and the simultaneous nature of the animal experiments will allow unprecedented clarity on the underlying source of the signal changes observed in fMRI. These animal studies are essential for providing new insights into the basis of human fMRI signals and data of this nature has not previously been available. The work in this proposal is novel in that it will directly inform measures of both evoked and spontaneous activity in terms of the underlying cell signal sources revealing the relative contributions of excitatory, inhibitory and glial cells to the fMRI signal. The implications of the work are multifaceted. This work will provide a platform for evaluating neurological models of disease. For example, mouse models of disease can be used to link to human data in diseases such as PTSD, depression, and autism, to name a few. It will also provide a firmer biological basis for understanding the node and network measures used in assessing the functional organization of the brain and will have important implications for the design of therapeutic interventions across a range of diseases.

项目摘要 该RFA旨在将跨学科团队汇集在一起​​，以专注于新颖，变革性和综合性 将彻底改变我们对收集数据的生物学和生物信息学内容的理解的努力 来自非侵入性人类功能性脑成像技术。我们的建议确实做到了。我们是一个 具有光遗传学专业知识的科学家的多学科团队，两个光子CA2+成像， 生物医学工程，分子生物学，动物和人fMRI，网络理论，数据分析和 造型。在这项工作中，我们将使用一种新颖的成像装置，将介镜成像结合在一起 整个空间的编码CA2+指示器具有很高的空间和高临时（25ms）的分辨率 转基因小鼠模型中的皮质和同时fMRI。这些动物实验被设计为 补充健康人类受试者的类似实验。动物实验的结果将 回答有关fMRI信号来源的几个长期问题。具体来说，使用成像，我们 将量化不同细胞群（兴奋性神经元，抑制性神经元和神经胶质细胞）的贡献 观察到的fMRI信号。我们将能够首次测试和验证图的应用 理论方法来分析人类fMRI数据，我们将基于 控制理论，用于从fMRI信号中提取更多信息。一套有力的精心控制的 小鼠的成像实验将为人类数据分析的几个方面提供信息。人类数据将 包含测试/重新测试组件，以确保结果复制并允许内置预测模型 一个数据集并在另一个数据集中进行了测试。这项工作真正桥接了规模和方式以及简单的性质 动物实验将使信号变化的潜在来源前所未有 在fMRI中观察到。这些动物研究对于提供人类fMRI基础的新见解至关重要 以前尚未获得这种性质的信号和数据。该提议中的工作是新颖的 将直接根据基础细胞信号来直接告知诱发活动和赞助活动的措施 来源揭示了兴奋性，抑制性和神经胶质细胞对fMRI信号的相对贡献。这 工作的含义是多方面的。这项工作将为评估神经系统模型提供一个平台 疾病。例如，疾病的小鼠模型可用于与疾病中的人类数据联系 PTSD，抑郁和自闭症，仅举几例。它还将为理解固件生物学基础 用于评估大脑功能组织的节点和网络措施，并将具有 对各种疾病的治疗干预措施设计的重要意义。