Depth-resolved Optical Imaging of Neural Action Potentials

描述（由申请人提供）：随着直接评估神经活动的新方法的发展成为迫切需要，各种光学技术正在研究用于高时空分辨率成像神经结构和功能。最近，新兴的光谱域光学相干断层扫描（OCT）技术使我们能够在毫秒时间尺度上同时检测无脊椎动物轴突不同深度的动作电位（AP）相关相位变化。我们还利用该技术在电压敏感染料染色的轴突中对AP进行深度定位，并构建了高灵敏度的极化敏感系统来测量AP传播过程中的延迟变化。这些技术还有一个额外的优势，那就是比许多其他测量方法侵入性更小，因为它们是在反射几何中工作的，这意味着源和检测器在神经的同一侧。长期目标是提供临床有用的无创神经功能测试。本项目的总体目标是开发相位和偏振敏感的OCT技术和对比度增强方法，用于各种神经活动的深度分辨成像，包括鱿鱼巨轴突、梭子鱼嗅觉神经、蝾螈和小鼠视网膜。目标包括发展关于光学记录信号的性质和起源的见解。目前，产生光信号的结构变化的机理尚不清楚。知识的缺乏阻碍了对神经活动评估的改进。此外，新技术和对比的发展对科学和临床应用至关重要。

DESCRIPTION (provided by applicant): As the development of new methods that directly assess neural activity becomes a pressing need, a variety of optical techniques is being investigated for imaging neural structure and function with high temporal and spatial resolutions. Recently, the emerging technology of spectral-domain optical coherence tomography (OCT) has allowed us to simultaneously detect action potential (AP) related phase changes at different depths from invertebrate axons on a millisecond time scale. We also utilized the technology for depth- localization of APs in axons stained with voltage-sensitive dyes, and constructed highly sensitivity polarization-sensitive systems for measuring retardance change during AP propagation. These techniques have the additional advantage of being less invasive than many other measurements, because they work in reflection geometry, which means the source and detector are on the same side of the nerve. The long term goal is to provide clinically useful noninvasive tests of nerve function. The overall objective of this project is to develop phase- and polarization-sensitive OCT techniques and contrast enhancement methods for depth-resolved imaging of neural activity in various preparations including squid giant axon, pike olfactory nerve, and salamander and mouse retinas. The objective includes development of insights about the nature and origin of the optically recorded signals. Presently, the mechanistic origins of the structural changes producing the optical signals are not known. The lack of knowledge hampers improvements in the assessment of neural activity. Furthermore, development of new techniques and contrasts is essential for scientific and clinical applications.