Noninvasive imaging-based electrophysiology using microelectronic devices

使用微电子设备进行基于无创成像的电生理学

• 批准号: 8658488
• 负责人: Alan Jasanoff
• 金额: $ 39.22万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658488
• 关键词: Action Potentials; Adhesives; Animals; Area; Artificial Intelligence; Bathing; Biological Neural Networks; Biology; Brain; Brain Diseases; Caliber; Cell Culture Techniques; Cell physiology; Cells; Cerebral cortex; Chemicals; Child Development; Contralateral; Contrast Media; Cultured Cells; Data; Detection; Devices; Diagnosis; Diagnostic; Education; Electrodes; Electronics; Electrophysiology (science); Electroplating; Engineering; Feedback; Geometry; Goals; Gold; Human; Image; Imaging Techniques; Incubators; Individual; Informatics; Injury; Knowledge; Life; Magnetic Resonance Imaging; Magnetism; Magnetoencephalography; Measurable; Measurement; Measures; Medicine; Methods; Microelectrodes; Modeling; Morphologic artifacts; Neurobiology; Neurons; Neurosciences; Organism; Performance; Personal Satisfaction; Phase; Physiology; Population; Positioning Attribute; Protocols documentation; Rattus; Relative (related person); Reporting; Sampling; Scanning; Series; Signal Transduction; Site; Slice; Techniques; Technology; Testing; Tissues; Validation; Variant; Work; base; brain research; density; design; electrical potential; improved; information processing; magnetic field; molecular imaging; nervous system disorder; neural stimulation; novel; optogenetics; programs; relating to nervous system; remediation; research study; sensor; somatosensory; tool; two-dimensional; voltage

DESCRIPTION (provided by applicant): The goal of this project is to establish a strategy that will make neuronal electrical signaling detectable via magnetic resonance imaging (MRI) at a whole-brain level. Our approach is built on the novel concept of using cell-adhesive micron-scale electronic devices to transduce neuronal potentials across the brain into magnetic field fluctuations. As part of our validation of these voltage-sensing microprobes, we also propose to implement a new, scalable method for simultaneous recording of MRI and electrophysiological data. The methods we propose to develop will be broadly applicable to problems in neurobiology, and will transform neuroscientists' ability to study integrative functions of the brain. Our microprobe approach will also help establish a new paradigm in diagnostic medicine and molecular imaging, where tiny machines, rather than conventional chemical contrast agents, will report on aspects of cellular physiology. Recent work has dem- onstrated that micron-scale electrodes, coated with cell-adhesive molecules and juxtaposed against cultured cells allow recording of millivolt-scale action potentials, comparable to intracellular recordings. The current induced in a microelectrode can be converted into a modest, transient magnetic field if it is channeled into an inductor. In Specific Aim 1, we will model the magnetic fields produced by feasible currents in spiral or solenoidal microcoils of defined geometry, compute predicted effects on MRI signal amplitude and phase as a function of microprobe distribution, and fabricate the microprobes themselves. Preliminary calculations indicate that localized, transient fields of about 10 nT could be produced in individual 10-turn microcoils of 1 5m diameter. Magnetic fields of this order are greater than endogenous neuronal fields detected in tech- nologies like magnetoencephalography, and have been shown previously to be measurable by MRI in some contexts. In Specific Aim 2, we will test the ability of our microprobes to report action potentials from neu- ronal populations in MRI. The microdevices wil first be applied to cultured neurons or neural tissue slices and placed in an MRI scanner. Data series will be obtained using multiple protocols to detect variations of MRI signal due to variations in neuronal activity. If experiments in culture are successful, microprobes will be site-specifically injected into the cerebral cortex of anesthetized rats, and tested in an somatosensory stimu- lation paradigm. In Specific Aim 3, we will establish a simultaneous MRI and conventional electrophysiology approach to validate the novel MRI voltage probes directly. Performing electrophysiology in an MRI scanner is complicated by artifacts induced by the scanning hardware, in particular due to switched gradient fields. To circumvent this problem, we will measure neuronal potentials using differential recording from pairs of channels on tetrodes or modified tetrodes. Once the in-scanner recording method has been refined, MRI- based and conventional electrophysiology data will be obtained and compared to assess performance of the voltage-sensing microprobes, and to guide further improvements, if necessary.

描述（由申请人提供）：该项目的目的是建立一种策略，该策略将通过磁共振成像（MRI）在整个脑水平上检测到神经元电信号传导。我们的方法建立在新的概念上，即使用细胞粘附的微米尺度电子设备将跨大脑的神经元电位转移到磁场波动中。作为对这些电压感应微探针的验证的一部分，我们还建议实施一种新的可扩展方法，以同时记录MRI和电生理数据。我们建议开发的方法将广泛适用于神经生物学的问题，并将改变神经科学家研究大脑综合功能的能力。我们的微探针方法还将有助于建立诊断医学和分子成像方面的新范式，在该诊断医学和分子成像中，微型机器（而不是常规的化学对比剂）将报告细胞生理学方面。最近的工作表明，用细胞粘附分子涂覆并与培养细胞并置的微米尺度电极可以记录与细胞内记录相媲美的毫伏型尺度的动作电位。如果将微电极中诱导的电流转换为适度的，瞬态磁场，如果将其引导到电感器中。在特定的目标1中，我们将对定义几何形状的螺旋或螺线管微线圈中可行电流产生的磁场进行建模，计算对MRI信号振幅和相位的预测影响，并根据微探针分布的函数，并构成微propoprobers本身。初步计算表明，可以在直径1 5m的单个10扭转微型机构中产生局部的瞬态瞬时场。该顺序的磁场大于在磁脑电图等技术学中检测到的内源性神经元场，并且在某些情况下已显示MRI可以测量。在特定的目标2中，我们将测试微探测报告在MRI中报告的动作电位的能力。该微发行版将首先应用于培养的神经元或神经组织切片，并放置在MRI扫描仪中。由于神经元活性的变化，将使用多种方案使用多种方案来检测MRI信号的变化。如果培养中的实验成功，则将微探针特异性地注射到麻醉大鼠的大脑皮层中，并在体感刺激范式中进行测试。在特定目标3中，我们将建立同时的MRI和常规电生理方法，以直接验证新型MRI电压探针。在MRI扫描仪中执行电生理学，这是由于扫描硬件引起的伪像，特别是由于切换梯度场。为了解决这个问题，我们将使用从四极管或修饰的四极管上的一对通道的差异记录来测量神经元电位。一旦完善了扫描仪记录方法，将获得基于MRI的和常规的电生理学数据并进行比较以评估电压感应微探针的性能，并在必要时指导进一步的改进。