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.

项目摘要：使用静止状态功能连通性（FC）分析的自发脑活动的功能映射 fMRI数据最近已成为绘制人脑功能的主要方法，并继续获得动力。但是fMRI是基于相对间接的脑血液动力学耦合到神经元活性和较慢（〜0.3 Hz）。此外，FC的生理基础是相对未解决的，使得FC的机制和含义通常不清楚。为了缺血性中风的示例，众所周知，缺血核周围的半骨发生了变化神经血管耦合（NVC），使FC缺陷的解释变得复杂。作为FC措施进一步扩展到大脑发育，衰老和疾病的研究，理解的重要性 FC的基本基础将增长。我们最近开发了功能的血流动力学映射使用光学固有信号成像（FCOI）的小鼠连通性，发现FCOI对几个敏感神经疾病，包括中风的小鼠模型和阿尔茨海默氏病。但是，与小鼠基因工程技术的出现，有新的机会扩展光学宽场成像到钙活性，该成像快速> 10倍，更直接地与神经活动耦合比血红蛋白。通过结合钙和血流动力学成像，有可能量化整个大脑区域的细胞特异性钙动力学与血液动力学之间的关系。进一步的并发钙和血红蛋白成像可能有助于解决有关影响的问题 NVC在中风等疾病和早期大脑发育中改变了NVC。但是，尚无成像已经开发了系统来检查整个小鼠皮层的这些丰富关系。在这个项目，我们将开发光学成像硬件和软件，以表征钙动态为基因编码的钙指标（GECI）设计的小鼠。对于示例申请功能网络正在迅速变化，我们将在中风恢复和大脑期间量化FC 开发，跟踪功能连通性和神经血管耦合（NVC）的进展。 AIM 1将发展荧光分子断层扫描（FMT）和弥散光学断层扫描（DOT）用于在小鼠中钙和血红蛋白同时映射的仪器。 AIM 2将优化系统高速FMT/小鼠脑功能的性能。 AIM 3将建立FMT/DOT 用GECIS映射小鼠中细胞特异性钙信号的功能网络。并发成像使用血红蛋白可以绘制神经血管耦合。在AIM 4中，确定可行性中风恢复和大脑发育的FMT/DOT。在这两种应用中，我们都将量化钙 FC和NVC改变对血红蛋白-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.