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开发成为迫切需要，正在研究各种光学技术，用于以高时间和空间分辨率成像神经结构和功能。近年来，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用电压敏感染料染色的轴突中对AP进行深度定位，并构建了用于测量AP传播期间延迟变化的高灵敏度偏振敏感系统。这些技术具有比许多其他测量更少侵入性的额外优势，因为它们在反射几何中工作，这意味着源和检测器位于神经的同一侧。长期目标是提供临床上有用的神经功能的非侵入性测试。该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，用于对包括鱿鱼巨轴突、梭子鱼嗅神经、蝾螈和小鼠视网膜在内的各种制剂中的神经活动进行深度分辨成像。目标包括发展有关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制起源尚不清楚。知识的缺乏阻碍了神经活动评估的改进。此外，新技术和对比剂的开发对于科学和临床应用至关重要。 公共卫生相关性：该提案的重点是在神经组织中的任何解剖结构损失或永久性损伤之前，对生理活动（功能）期间的瞬态结构变化进行成像。通过开发新的非接触式非侵入性光学成像技术，我们打算找到最有利的神经活动的光学措施，可用于神经疾病的早期检测。

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. PUBLIC HEALTH RELEVANCE: The focus of this proposal is to image transient structural changes during physiological activity (function) prior to any anatomical structural loss or permanent damage in neural tissue. By developing novel non-contact non-invasive optical imaging techniques, we intend to find the most favorable optical measures of neural activity that can be utilized for early detection of neural diseases.