Direct MRI of Neuroelectric Activity for Animal Neuroimaging

动物神经影像神经电活动的直接 MRI

• 批准号: 8213739
• 负责人: Trong-Kha Truong
• 金额: $ 31.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213739
• 关键词: Action Potentials; Address; Animal Experimentation; Animal Model; Animals; Area; Brain; Brain region; Caliber; Cell Death; Complex; Coupling; Diagnosis; Electronics; Experimental Designs; Fiber Optics; Frequencies; Functional Magnetic Resonance Imaging; Genetic; Goals; Human; Image; Ion Channel; Light; Magnetic Resonance Imaging; Maps; Mental disorders; Methods; Molecular Genetics; Motor Cortex; Nervous System Physiology; Neural Conduction; Neurons; Neurosciences; Neurosciences Research; Noise; Physiological; Play; Prevention; Resolution; Role; Solutions; Specificity; Surface; Techniques; Time; Transgenic Mice; Validation; Visible Radiation; Water; afferent nerve; base; blood oxygen level dependent; cell injury; data acquisition; density; design; hemodynamics; improved; in vivo; magnetic field; median nerve; meetings; millisecond; mouse model; nervous system disorder; neural circuit; neuroimaging; novel; olfactory bulb; public health relevance; relating to nervous system

DESCRIPTION (provided by applicant): Neuroscience research on animal models plays a fundamental role in improving the diagnosis and treatment of human neurological disorders, because of the capacity for genetic and pharmacological manipulations. Among the most widely used methods to investigate brain function, electrophysiological recordings benefit from a high temporal resolution, but are invasive and have a limited spatial coverage. Conversely, blood oxygenation level-dependent functional MRI is noninvasive and provides full brain coverage, but cannot quantitatively and accurately localize neural activity in space and time because of the complex neurovascular coupling. A novel MRI technique, termed Lorentz effect imaging (LEI), which detects the ionic currents and surrounding water molecules induced by neural activity, was proposed to address these limitations. This technique has been applied to image ionic currents in solution with current densities similar to those induced by neural activity as well as sensory nerve action potentials in the human median nerve in vivo with a millisecond temporal specificity. Given these promising results, it is hypothesized that LEI can be further developed to image neural activity in the brain with a high spatial and temporal specificity across functional networks. The goal of this project is to develop such a noninvasive and specific functional neuroimaging technique for animal research, which would have a significant impact in neuroscience. Because of potential confounding factors such as physiological noise, the application of LEI to the brain requires a further increase in sensitivity. In addition, its validation requires a robust stimulation paradigm that can be accurately controlled in space and time. These two requirements can be met by using a 7 T animal MRI scanner with a significantly higher field strength and gradient amplitude as compared to the human scanner used previously, as well as a novel transgenic mouse model expressing the light-activated ion channel Channelrhodopsin-2 (ChR2) in selected neurons throughout the brain, which can be activated in vivo by photostimulation with visible light. Three specific aims are proposed. Aim 1 is to demonstrate the feasibility of LEI to image neural activity in the brain in vivo by photostimulating the cortical surface of anesthetized ChR2 transgenic mice and by using a careful experimental design to remove any confounding hemodynamic modulations. Aim 2 is to demonstrate the ability of LEI to accurately localize neural activity in space and time by varying the spatial extent or timing of the photostimulation. Aim 3 is to demonstrate the ability of LEI to track and map neural activity across functional networks by photostimulating the olfactory bulb and by using different activation paradigms designed to selectively track neural activity in different regions of the olfactory neural circuit or to simultaneously map all functionally connected areas. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop a novel MRI technique for animal functional neuroimaging combining the high temporal specificity of electrophysiological recordings with the noninvasiveness and high spatial coverage inherent in MRI. Such a technique has the potential to noninvasively track and map neural activity in vivo with a high spatial and temporal specificity across the whole brain, which would significantly enhance our ability to investigate the function of the nervous system and hence improve the understanding, prevention, diagnosis, and treatment of many neurological and psychiatric disorders.

描述（由申请人提供）：动物模型的神经科学研究在改善人类神经系统疾病的诊断和治疗方面起着重要作用，因为它具有遗传和药理操作的能力。在研究脑功能的最广泛使用的方法中，电生理记录得益于高时间分辨率，但具有侵入性并且空间覆盖有限。相反，依赖于血氧水平的功能性MRI是无创的，可以提供全脑覆盖，但由于复杂的神经血管耦合，无法定量和准确地定位空间和时间上的神经活动。提出了一种新的MRI技术，称为洛伦兹效应成像（LEI），它可以检测由神经活动引起的离子电流和周围水分子，以解决这些限制。该技术已被应用于成像溶液中的离子电流，其电流密度类似于神经活动引起的电流密度，以及人体正中神经的感觉神经动作电位，具有毫秒级的时间特异性。鉴于这些有希望的结果，我们假设LEI可以进一步发展，以在功能网络中具有高空间和时间特异性的大脑神经活动成像。该项目的目标是开发一种用于动物研究的非侵入性和特异性功能神经成像技术，这将对神经科学产生重大影响。由于生理噪声等潜在的混杂因素，将LEI应用于大脑需要进一步提高灵敏度。此外，它的验证需要一个强大的刺激模式，可以在空间和时间上精确控制。与之前使用的人类扫描仪相比，使用具有更高场强和梯度振幅的7 T动物MRI扫描仪，以及在整个大脑中选定的神经元中表达光激活离子通道Channelrhodopsin-2 （ChR2）的新型转基因小鼠模型，可以满足这两个要求，该通道可以通过可见光光刺激激活。提出了三个具体目标。目的1是通过光刺激被麻醉的ChR2转基因小鼠的皮质表面，并使用仔细的实验设计来去除任何混淆的血流动力学调节，来证明LEI在体内大脑中成像神经活动的可行性。目的2是通过改变光刺激的空间范围或时间来证明LEI在空间和时间上精确定位神经活动的能力。目的3是证明LEI通过光刺激嗅球和使用不同的激活范式来选择性地跟踪嗅神经回路不同区域的神经活动或同时绘制所有功能连接区域的神经活动，从而跟踪和绘制跨功能网络的神经活动的能力。