In-vivo optical imaging of neurovascular coupling and cerebral metabolism

神经血管耦合和脑代谢的体内光学成像

基本信息

批准号：
7874281
负责人：
Elizabeth M. C. Hillman
金额：
$ 3.78万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-15 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7874281
关键词：
Acute Address Alzheimer&apos s Disease Animals Astrocytes Blood Vessels Blood capillaries Blood flow Brain Brain imaging Calcium Cell physiology Cells Cerebrum Conflict (Psychology)Contrast Sensitivity Coupling Cytochromes Data Degenerative Disorder Development Disease Disease Progression Diving Dyes Elements Energy Metabolism Energy Supply Fluorescence Functional Magnetic Resonance Imaging Future Goals Heterogeneity Histology Home environment Image Imaging Device Imaging Techniques Imaging technology Impairment In Vitro Interneurons Label Lead Length Life Link Location Maps Measurement Metabolic Metabolism Microscope Microscopy Modality Modeling NADH Neurons Neurosciences Optical Tomography Optics Oxidation-Reduction Oxyhemoglobin Physiology Plasma Process Proteins Rage Regulation Reporting Research Resolution Smooth Muscle Speed Stimulus Structure System Three-Dimensional Imaging Time Transgenic Mice Transgenic Model Validation Work absorption age related neurodegeneration arteriole base capillary constriction deoxyhemoglobin glucose analog glucose uptake hemodynamics imaging modality in vivo insight mind control neuroimaging optical imaging response spatiotemporal submicron tool two-photon voltage

项目摘要

DESCRIPTION (provided by applicant): A local increase in cortical blood flow is widely accepted to report the presence and location of neuronal activity in the brain. This hemodynamic response is the basis of functional brain imaging methods such as functional Magnetic Resonance Imaging (fMRI). Yet the way that the brain controls these blood flow changes, and even the underlying purpose of the hemodynamic response are still unknown. There is growing evidence that impairments in regulation of the hemodynamic response may underlie age-related neurodegeneration, and can be linked to the progression of diseases such as Alzheimer's. A comprehensive model of the mechanisms underlying the coupling between neuronal and hemodynamic responses in the brain is urgently needed. The lack of a conclusive model to date is due, in part, to the difficulties faced in imaging the normal, functioning, intact brain in-vivo. In-vitro studies which investigate potential mechanisms in isolation are uniformly difficult to compare with other in-vitro results, and to reconcile with in-vivo observations. However, it is highly challenging to develop in-vivo imaging paradigms capable of achieving sufficient resolution, sensitivity and contrast to gain a complete picture of the neuronal, metabolic and vascular processes which together generate the hemodynamic response to activation. We have developed a suite of advanced optical imaging and microscopy tools for in-vivo examination of neurovascular coupling. We plan to exploit a wide range of optical contrasts including oxy- and deoxyhemoglobin, calcium sensitive dyes, cell-specific dyes, transgenic mice expressing fluorescent proteins, and intrinsically fluorescent substrates of energy metabolism such as NADH and FAD. We propose to refine and apply our imaging tools to address the following two fundamentally important questions: 'How is the cortical vasculature physically modulated?' and 'Why does the hemodynamic response happen?' Our multi-scale and multi-parametric imaging approaches offer the chance to both fully characterize the physical mechanisms which modulate and control the hemodynamic response, and to investigate the metabolic basis of the response and its relation to energy supply and demand at a cellular level. We believe that these studies will lead to a comprehensive model of neurovascular coupling. We also anticipate that the imaging techniques that we develop, and our careful characterization of the healthy brain, will clear the way for future in-vivo research into the cellular, metabolic and neurovascular underpinnings of disease.

描述（由申请人提供）：广泛接受皮质血流的局部增加，以报告神经元活性在大脑中的存在和位置。这种血液动力学反应是功能性脑成像方法的基础，例如功能磁共振成像（fMRI）。然而，大脑控制这些血流的方式，甚至血液动力学反应的根本目的仍然未知。越来越多的证据表明，调节血液动力学反应的损害可能是与年龄相关的神经变性的基础，并且可以与诸如阿尔茨海默氏症等疾病的进展有关。迫切需要大脑中神经元和血液动力学反应之间耦合的机制的综合模型。迄今为止缺乏结论性模型的部分原因是在成像正常，功能性，完整的大脑体内所面临的困难。在隔离中研究潜在机制的体外研究很难与其他体外结果进行比较，并与体内观察结果和解。但是，开发能够实现足够的分辨率，敏感性和对比度的体内成像范式的挑战是高度挑战，以获得神经元，代谢和血管过程的完整图片，从而共同产生对激活的血液动力学反应。我们开发了一套高级光学成像和显微镜工具，用于对神经血管耦合的体内检查。我们计划利用各种光学对比度，包括氧和脱氧血红蛋白，钙灵敏染料，细胞特异性染料，表达荧光蛋白的转基因小鼠以及诸如NADH和FAD等能量代谢的本质荧光底物。我们建议完善并应用我们的成像工具来解决以下两个重要的问题：“皮质脉管系统如何物理调节？”和“为什么血液动力学反应发生？”我们的多尺度和多参数成像方法为既充分表征调节和控制血液动力学反应的物理机制提供了机会，并研究反应的代谢基础及其与细胞水平的能源供应的关系。我们认为，这些研究将导致神经血管耦合的全面模型。我们还预计，我们开发的成像技术以及对健康大脑的仔细表征将为未来对疾病的细胞，代谢和神经血管内部研究的体内研究扫清道路。