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Space-division multiplexing optical coherence tomography for large-scale, millisecond resolution imaging of neural activity

用于神经活动大规模、毫秒分辨率成像的空分复用光学相干断层扫描

基本信息

批准号：
9144804
负责人：
YEVGENY BERDICHEVSKY
金额：
$ 23.41万
依托单位：
LEHIGH UNIVERSITY
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

项目摘要

DESCRIPTION There is a great interest in imaging neuronal activity based on changes in fast intrinsic optical signals (e.g. changes in light scattering and phase) that occur on a millisecond timescale. Fast intrinsic optical signals are related to alteration in the complex refractive index and small volume changes near the neuron membrane, in response to the rapid osmotic changes associated with ion fluxes during action potentials. Optical coherence tomography (OCT) is an emerging biomedical imaging technology that provides label-free and depth-resolved images with micron-scale spatial resolution and sub-millisecond temporal resolution. OCT relies on detection of intrinsic optical contrast, eliminating the need for potentially toxic exogenous contrast agents or genetically- encoded indicators. OCT achieves over 100 dB sensitivity, enabling it to detect weak scattering changes associated with neuronal activity. In addition, OCT has extremely good phase sensitivity (<one millirad, corresponding to an optical path length change of ~100 pm), making it possible to detect nanometer-scale membrane displacement associated with neural action potentials with over 10x signal-to-noise ratio. Recently, our group developed a space-division multiplexing OCT (SDM-OCT) technology which allows parallel and synchronized imaging from multiple sample locations. In this exploratory program, we plan to evaluate the feasibility of using high resolution (<3 μm) and ultrahigh speed (3.2M A-scans/s) SDM-OCT technology to image and characterize activity-dependent fast intrinsic optical signal changes, especially phase changes. Validation experiments will be conducted using in vitro rat 2D neural cultures and 3D organotypic hippocampal cultures to correlate fast intrinsic optical signal changes imaged with SDM-OCT with electrophysiological stimulation and recording of neural activities. Since each vertical cross sectional OCT image will contain hundreds of neurons, intrinsic optical signals from thousands of neurons can be recorded simultaneously using the space-division multiplexing technology. If successful, this label-free imaging technology can become a powerful platform to investigate behavior of thousands of neurons in a network simultaneously, with the potential to significantly impact fundamental brain research.

描述基于在毫秒时间尺度上发生的快速内在光学信号的变化（例如，光散射和相位的变化）对神经元活动进行成像具有极大的兴趣。快速的本征光信号与复折射率的变化有关以及神经元膜附近的小体积变化，响应于动作电位期间与离子通量相关的快速渗透变化。光学相干层析成像（OCT）是一种新兴的生物医学成像技术，能够提供无标记的深度分辨图像，具有微米级的空间分辨率和亚毫秒级的时间分辨率。OCT依赖于对内在光学对比度的检测，消除了对潜在有毒的外源性造影剂或遗传编码指示剂的需要。OCT达到超过100 dB的灵敏度，使其能够检测与神经元活动相关的弱散射变化。此外，OCT具有非常好的相位灵敏度（<1毫拉德，对应于~100 μ m的光程长度变化），使得可以以超过10倍的信噪比检测与神经动作电位相关的纳米级膜位移。最近，我们的团队开发了一种空分复用OCT（SDM-OCT）技术，该技术允许从多个样品位置进行并行和同步成像。在这个探索性项目中，我们计划评估使用高分辨率（<3 μm）和高速（3.2M A扫描/s）SDM-OCT技术来成像和表征活性相关的快速内在光学信号变化，特别是相位变化的可行性。将使用体外大鼠2D神经培养物和3D器官型海马培养物进行验证实验，以将SDM-OCT成像的快速内在光学信号变化与电生理刺激和神经活动记录相关联。因为每个垂直交叉断层OCT图像将包含数百个神经元，使用空分复用技术可以同时记录来自数千个神经元的内在光信号。如果成功，这种无标记成像技术可以成为一个强大的平台，同时研究网络中数千个神经元的行为，并有可能对基础大脑研究产生重大影响。