MAPPING FUNCTIONAL CONNECTIVITY WITH FLUORESCENCE MOLECULAR TOMOGRAPHY

使用荧光分子断层扫描绘制功能连接图

基本信息

批准号：
10160971
负责人：
JOSEPH P CULVER
金额：
$ 56.7万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10160971
关键词：
ARHGEF5 gene Aging Alzheimer&apos s Disease Anatomy Astrocytes Biological Assay Blood Blood Vessels Brain Brain region Calcium Calcium Signaling Cells Computer software Coupled Coupling Data Development Disease Evolution Formulation Functional Magnetic Resonance Imaging Gene Expression Genetic Engineering Genetically Engineered Mouse Glial Fibrillary Acidic Protein Grant Head Hemoglobin Histology Human Image Ischemic Stroke Light Lighting Maps Measures Methods Modeling Molecular Monte Carlo Method Mus Nature Neurons Noise Optical Tomography Optics Pattern Performance Physiological Physiology Reproducibility Rest Sampling Signal Transduction Specificity Speed Stroke Structure System Techniques Technology Uncertainty Validation base calcium indicator cell type cerebral hemodynamics contrast imaging data analysis pipeline data modeling design detector diffuse optical tomography flexibility fluorescence molecular tomography hemodynamics imaging system improved in vivo evaluation instrumentation mouse model nervous system disorder neuroimaging neurovascular coupling non-invasive imaging optical imaging postnatal relating to nervous system stroke model stroke recovery tomography

项目摘要

Project Summary: Functional mapping of spontaneous brain activity with resting-state functional connectivity (FC) analysis of fMRI data has recently become a dominant approach to mapping human brain function and continues to gain momentum. However fMRI is based on cerebral hemodynamics that is relatively indirectly coupled to neuronal activity and much slower (~0.3 Hz). Further the physiological underpinnings of FC are relatively un-resolved, such that the mechanisms and implications altered FC are often unclear. For example in ischemic stroke, it is well known that the penumbra surrounding the ischemic core has altered neurovascular coupling (NVC), complicating the interpretation of the FC deficits. As FC measures are extended further into studies of brain development, aging and disease, the importance of understanding the fundamental basis for FC will grow. We recently developed hemodynamic mapping of functional connectivity in mice using optical intrinsic signal imaging (fcOIS), and found fcOIS sensitive to several neurological diseases, including mouse models of stroke and Alzheimer's disease. However, with the advent of genetic engineering techniques for mice, there are new opportunities for extending optical wide-field imaging to calcium activity, which is >10x faster and more directly coupled to neural activity than hemoglobin. By combining calcium and hemodynamic imaging, there is the potential to quantify the relationship between cell-specific calcium dynamics and hemodynamics throughout brain regions. Further concurrent calcium and hemoglobin imaging could help resolve questions about the impact of altered NVC in diseases such as stroke, and in early brain development. However, as yet, no imaging system has been developed to examine these rich relationships throughout the mouse cortex. In this project, we will develop optical imaging hardware and software for characterizing calcium dynamics in mice engineered for genetically encoded calcium indicators (GECI's). For exemplar applications where the functional networks are changing quickly, we will quantify FC during stroke recovery and brain development, tracking the progression of both functional connectivity and neurovascular coupling (NVC). Aim 1 will develop fluorescence molecular tomography (FMT) and diffuse optical tomography (DOT) instrumentation for concurrent mapping of calcium and hemoglobin in mice. Aim 2 will optimize system performance for high speed FMT/DOT of mouse brain function. Aim 3 will establish FMT/DOT for mapping the functional networks of cell-specific calcium signals in mice with GECIs. Concurrent imaging with hemoglobin will enable mapping of neurovascular coupling. In aim 4, with establish feasibility of FMT/DOT in both stroke recovery and brain developmental. In both applications we will quantify calcium- FC and the influence of altered NVC on hemoglobin-FC.

项目概要：通过静息态功能连接 (FC) 分析绘制自发大脑活动的功能图最近，功能磁共振成像数据已成为绘制人类大脑功能图谱的主要方法，并且仍在继续获得动力。然而，功能磁共振成像基于脑血流动力学，相对间接与神经元活动耦合并且速度慢得多（~0.3 Hz）。进一步了解 FC 的生理基础相对而言尚未解决，因此改变 FC 的机制和影响通常不清楚。为了以缺血性中风为例，众所周知，缺血性核心周围的半影已经改变神经血管耦合（NVC），使 FC 缺陷的解释变得复杂。由于 FC 措施是进一步扩展到大脑发育、衰老和疾病的研究中，理解的重要性 FC的基本基础将会增长。我们最近开发了功能性血流动力学图使用光学内在信号成像 (fcOIS) 检测小鼠的连接性，并发现 fcOIS 对多种信号敏感神经系统疾病，包括中风和阿尔茨海默病的小鼠模型。然而，随着小鼠基因工程技术的出现，为扩展光学提供了新的机会对钙活动进行广域成像，速度快 10 倍以上，并且与神经活动更直接耦合比血红蛋白。通过结合钙和血流动力学成像，有可能量化整个大脑区域细胞特异性钙动力学和血流动力学之间的关系。进一步并发的钙和血红蛋白成像可以帮助解决有关影响的问题 NVC 在中风等疾病和早期大脑发育中发生改变。但目前还没有成像已经开发出系统来检查整个小鼠皮层的这些丰富的关系。在这个项目，我们将开发光学成像硬件和软件，用于表征钙动力学基因编码钙指示剂（GECI）的小鼠。对于示例应用程序，其中功能网络正在快速变化，我们将量化中风恢复期间的 FC 和大脑开发，跟踪功能连接和神经血管耦合（NVC）的进展。目标1将开发荧光分子断层扫描（FMT）和扩散光学断层扫描（DOT）用于同时绘制小鼠钙和血红蛋白图谱的仪器。目标2将优化系统小鼠大脑功能的高速 FMT/DOT 性能。目标 3 将建立 FMT/DOT 用 GECI 绘制小鼠细胞特异性钙信号的功能网络。并发成像与血红蛋白的结合将能够绘制神经血管耦合图。在目标 4 中，建立可行性 FMT/DOT 在中风恢复和大脑发育中的作用。在这两种应用中，我们都会量化钙- FC 和改变的 NVC 对血红蛋白-FC 的影响。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

DOI：
10.1093/cercor/bhx298
发表时间：
2018-01-01
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
0
作者：
Bauer AQ;Kraft AW;Baxter GA;Wright PW;Reisman MD;Bice AR;Park JJ;Bruchas MR;Snyder AZ;Lee JM;Culver JP
通讯作者：
Culver JP

Separability of calcium slow waves and functional connectivity during wake, sleep, and anesthesia.