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Capabilities of MRI-Based Neural Current Imaging for Human Brain Mapping

基于 MRI 的神经电流成像用于人脑绘图的能力

基本信息

批准号：
9145675
负责人：
YOUNG R KIM
金额：
$ 26.08万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9145675
关键词：
Affect Animal Experiments Animal Model Attention Brain Mapping Breathing Bypass Carbogen Carbon Dioxide Characteristics Clinical Research Complex Control Animal Coupling Detection Development Dose Electroencephalography Electrophysiology (science)Environmental air flow Frequencies Functional Magnetic Resonance Imaging Genes Head Health Human Hypercapnia Hyperoxia Image Imaging Techniques Investigation Location Magnetic Resonance Imaging Magnetoencephalography Maps Measures Methods Modality Modeling Nature Nervous system structure Neurons Neurosciences Optics Output Preparation Pyramidal Cells Rattus Research Project Grants Resolution Retinal blind spot Signal Transduction Somatosensory Cortex Source Stimulus Surface Synapses Technology Testing base blood oxygen level dependent electric field hemodynamics imaging modality magnetic field millisecond neurotransmission non-invasive imaging novel optogenetics relating to nervous system research study response success tool

项目摘要

DESCRIPTION (provided by applicant): In this proposal we leverage our recent developments in MRI acquisition methods and new animal models to attempt direct detection of neuronal currents with Magnetic Resonance Imaging (MRI). If successful, this project will have a high impact for scientific investigations of the nervous system, forming a powerful new tool for human neuroscience by supplementing the commonly applied hemodynamic based MR blood oxygenation level dependent (BOLD) functional MRI (fMRI) technique. Although fMRI is a primary tool for human neuroscience, it has severe shortcomings primarily arising from the complex coupling between neuronal activity (electrophysiology) and the hemodynamic response. Although the two are correlated, it is clear that information is lost when viewed through the "hemodynamic filter." In short, we seek a true MR based "non-invasive electrophysiology." Other non-invasive imaging modalities such as Magnetoencephalography (MEG) and Electroencephalography (EEG) do directly measure the neuronal activity in the form of the electric and magnetic fields produced by post-synaptic currents. While proven clinical and research tools, they also have limitations. Because they detect the field outside the head, they are sensitive only to large groups of neurons firing coherently with certain total post-synaptic current distributions. For example MEG is not sensitive to currents oriented radially with respect to the spherical head. The currents derive from pyramidal cells oriented normal to the cortical surface and the non-radial constraint causes multiple "blind spots" where the cortex folds in such a way that the pyramidal cells are oriented radially. EEG shares a similar problem. Finally, both modalities share limited spatial resolution complicated by an "ill posed inverse problem" which makes it impossible to determine the source locations without assumptions about their nature and distribution. The net effect is a modality with direct access to the temporal dynamics, but limited imaging ability compared to MRI. In this proposal, we outline a research project that pursues a novel MRI technique for the direct detection of neuronal currents. Its successful development would bypass many of the problems of MEG and EEG by probing the neuronal magnetic fields locally within each MRI voxel thus providing the high spatial resolution without the complications of the hemodynamic filter. Many attempts using MRI have been pursued over the last 15 years without clear success. We propose a new MR method based on the ability of a spin- lock MRI sequence (stimulus-induced rotary saturation: SIRS) to interact resonantly with magnetic fields oscillating at 10-100Hz. The sensitivity to oscillating fields is a significant improvement over other MR detection methods which require un-realistic DC fields. While we have shown that the sequence's minimum detection threshold is as low as the previous methods, it is nevertheless an exploratory proposal that will benefit from a concerted effort and a strong, readily controllable stimulus. Thus, we plan to test our method using an optogenetic rat model we have previously used for fMRI. In this preparation, neurons in somatosensory cortex are transfected to express ChannelRhodopsin-2 (ChR2) channels that excite neurons when illuminated. We show that optical stimulation produces extremely strong electrophysiological neural signals in synchrony with controlled optical stimuli. The optogenetic model is MR compatible allows millisecond control of the activation and elicits strong coherence of the neuronal firing compared to other stimuli. We propose a focused investigation using carefully controlled animal experiments to avoid contamination with the standard hemodynamic signal. For example, using both electrophysiology and fMRI, we demonstrated that the complete elimination of concomitant BOLD activation can be achieved via carbogen inhalation (CO2/O2) in rat models. As a central focus of this proposal, SIRS will be implemented and used to detect neuroelectric signals in the rat models transfected with ChR2 genes. Particular attention will be paid to remove confounders such as hemodynamic MRI signals in conjunction with independent electrophysiology to verify the characteristics of neural activities induced by optogenetics. The output of this 2 year project will be a validated MRI method that can then be used to quantify and spatially map the electrophysiological activity. Aim 1: Optimize carbogen (5% CO2/ 95% O2) dose in optogenetically modified rats to eliminate BOLD activation while maintaining the neuroelectric activity in response to optogenetic stimuli. We hypothesize that: Inhalation of carbogen removes the BOLD activation induced by optogenetic stimuli; Inhalation of carbogen does not affect the electrophysiological activity induced by optogenetic stimuli. Aim 2: Application of the Stimulus Induced Rotary Saturation (SIRS) acquisition to optogentically modified rats using long block duration experiments capturing neuronal current effects. We hypothesize that: During systemic hyperoxia/hypercapnia, optogenetic stimuli produce SIRS-based MRI signal; The optical stimulation amplitude is proportional to the neural activity; Optical stimulation with unmatched frequency does not result in SIRS-based neural signal.

描述（由申请人提供）：在本提案中，我们利用我们在MRI采集方法和新动物模型方面的最新进展，尝试使用磁共振成像（MRI）直接检测神经元电流。如果成功，该项目将对神经系统的科学研究产生重大影响，通过补充常用的基于血液动力学的MR血氧水平依赖（BOLD）功能MRI（fMRI）技术，为人类神经科学形成一个强大的新工具。虽然功能磁共振成像是人类神经科学的主要工具，它有严重的缺点，主要是由神经元活动（电生理学）和血液动力学反应之间的复杂耦合引起的。虽然两者是相关的，但很明显，当通过“血流动力学过滤器”查看时，信息会丢失。简而言之，我们寻求一种真正的基于MR的非侵入性电生理学。“其他非侵入性成像方式，如脑磁图（MEG）和脑电图（EEG），确实直接测量突触后电流产生的电场和磁场形式的神经元活动。虽然经过验证的临床和研究工具，但它们也有局限性。因为它们检测头部外部的场，所以它们只对具有特定总突触后电流分布的大群神经元一致性放电敏感。例如，MEG对相对于球形头部径向定向的电流不敏感。电流源自定向成垂直于皮质表面的锥体细胞，并且非径向约束导致多个“盲点”，其中皮质以锥体细胞径向定向的方式折叠。EEG也有类似的问题。最后，这两种方式共享有限的空间分辨率复杂的“不适定的逆问题”，这使得它不可能确定的源位置，而不假设其性质和分布。净效应是一种可直接访问时间动态的模态，但与MRI相比，成像能力有限。在这个建议中，我们概述了一个研究项目，追求一种新的MRI技术的神经元电流的直接检测。它的成功开发将绕过MEG和EEG的许多问题，通过探测每个MRI体素内的局部神经元磁场，从而提供高空间分辨率，而没有血液动力学滤波器的并发症。在过去的15年里，使用MRI进行了许多尝试，但没有明显的成功。我们提出了一种新的MR方法的基础上的自旋锁定MRI序列（刺激诱导旋转饱和：SIRS）的能力，以共振相互作用的磁场振荡在10- 100赫兹。对振荡场的灵敏度是对需要不真实的DC场的其他MR检测方法的显著改进。虽然我们已经表明，该序列的最低检测阈值是低如以前的方法，它仍然是一个探索性的建议，将受益于协调一致的努力和强大的，容易控制的刺激。因此，我们计划使用我们以前用于fMRI的光遗传学大鼠模型来测试我们的方法。在该制备中，将躯体感觉皮层中的神经元转染以表达在照明时兴奋神经元的ChR 2通道。我们表明，光学刺激产生非常强的电生理神经信号与控制的光学刺激同步。与其他刺激相比，光遗传学模型是MR兼容的，允许对激活进行毫秒级控制，并增强神经元放电的连贯性。我们建议使用仔细控制的动物实验进行重点调查，以避免标准血流动力学信号的污染。例如，使用电生理学和功能磁共振成像，我们证明了伴随BOLD激活的完全消除可以通过在大鼠模型中吸入二氧化碳（CO2/O2）来实现。作为该提案的中心焦点，SIRS将被实施并用于检测ChR 2基因转染的大鼠模型中的神经电信号。将特别注意消除混杂因素，如血液动力学MRI信号与独立的电生理学相结合，以验证光遗传学诱导的神经活动的特征。该2年项目的输出将是一种经确认的MRI方法，然后可用于量化和空间映射电生理活动。目标1：优化光遗传学修饰大鼠中的卡波姆（5%CO2/95%O2）剂量，以消除BOLD激活，同时保持响应于光遗传学刺激的神经电活性。我们假设：吸入Carbogen可消除光遗传学刺激诱导的BOLD激活;吸入Carbogen不影响光遗传学刺激诱导的电生理活性。目标二：使用长阻滞持续时间实验捕获神经元电流效应，将刺激诱导旋转饱和（SIRS）采集应用于光遗传修饰的大鼠。我们假设：在全身性高氧/高碳酸血症期间，光遗传学刺激产生基于SIRS的MRI信号;光刺激幅度与神经活动成比例;光刺激幅度与神经活动成比例。具有不匹配频率刺激不会产生基于SIRS的神经信号。