神经细胞放电动力学行为的全域光相位成像分析方法与技术

Dynamical analysis of the firing patterns of neurons is of great magnificance in many research fields, such as neuroscience, information science, clinical application and so on. Traditional techniques are still insufficient for mechanism analysis in multi-dimension as well as for potential measurement in continuity. This subject will study the firing behaviors of neurons in view of quantitative phase microscopy. Its main contents are presented as follows: The characteristics of physical structure and optical property of neurons will be investigated based on quantitative phase imaging in this subject. Phase models will be established according to the distribution of refractive index and thickness of the neurons. The exploration of the various effects of firing on the refractive index will be made to reveal the interaction between membrane potential (calcium ion concentration) and refractive index as well as thickness. Especially, the analysis will be made of the dynamic relationship between the characters of phase and the electrical parameters of the neurons. Technology requirements of continuous sampling for the universe of neurons will be given, and the full-field phase microscopic imaging device which matches this demand will be set up. Furthermore, the recognition methods of effective phase characteristic as well as the ultrafast extracted and retrieval process of the phase informations will be discussed. Finally, the dynamic equations expressed by phase characteristic and the corresponding analysis method will be proposed in this subject. This work will achieve the transient and full-field dynamical analysis of the firing patterns of neurons based on quantitative phase microscopy. It can make up for the deficiency of traditional method and provide a new way to research the dynamical mechanism of firing patterns of neurons.

神经细胞放电动力学行为的研究在神经科学、信息科学研究和临床应用等领域有着重要的意义。传统动力学研究手段及电位检测技术在参数分析多维性及空间刻画连续性等方面尚显不足。本项目拟基于光相位理论及其显微成像技术，分析神经细胞物理结构和光学性质特征，建立其折射率和厚度表征下的光相位模型；分析电活动下多样性作用对折射率的影响，阐明作用机理，紧扣神经细胞膜电位-离子浓度关键物理量，探明其与细胞光折射率及成像厚度的关联，建立光相位特征量-电参量动态关系；提出全域细胞连续采样技术要求，研发匹配的全场瞬态相位成像装置，给出有效相位参量识别方法，提出可连续位点采样的相位快速提取、重建及计算方法；依据电特征-光相位联系的本质，构建光相位参量刻画下的动力学方程，给出求解和演化分析方法。从理论和实验两方面实现光相位表述下的神经细胞全域放电动力学行为瞬态分析，弥补传统方法的不足，为神经细胞放电活动分析提供一种新方法。

神经元的放电活动与其形态结构、细胞的跨膜物质输运等密切相关，是生物神经系统信号传递的基础，在神经科学、信息科学研究和临床应用等领域有着重要的意义。本项目紧密围绕神经元放电活动的光相位检测这一主题，从理论推导、数值仿真和实验检测等多个角度，在神经元动力学和光相位模型建立、相位信息获取与分析、样品形态结构重建和动态活动刻画、成像系统设计与搭建等多个方面开展了研究。主要内容如下：基于几类神经元动力学模型分析了放电活动中离子浓度振荡的动力学特征，探究了神经元放电活动的物理机制，在挖掘生物学、动力学、电学、光学等参量内在联系的基础上建立了神经元光相位模型并仿真分析了其相位分布特征；基于相移干涉成像技术提出了可满足生物细胞动力学现象检测要求的微分相位恢复方法，就双波长干涉成像技术下干涉强度方程求解困难的问题，提出波-相纠缠关系并阐释其机制，快速地同时复原出每个波长对应的相位信息；建立了仅需两幅样品相位分布图的三维亚结构形态层析重建算法，基于数字图像边缘检测理论提出了亚细胞结构表面形貌快速重构方法；给出了样品浓度对其折射率及光相位分布的动态调制规律，构建了一种基于相位信息表征样品动态活动的采样检测方法；开展光相位成像实验，针对实验中多种因素的影响，对相位数据采集、相位信息解构等理论方法提出了相应的补充和修正技术方案，并对所提出的细胞空间形貌获取方法和动态相位采样检测方法等进行了验证；针对光相位成像对信号稳定性、抗噪性等方面的需求设计搭建了所用元件少易于实现的共光路干涉成像装置，针对光相位信息和散射信息在亚细胞结构识别中各自的优势和不足，设计了整合散射-相位成像的双参量同步检测系统以提高快速识别准确度。上述工作可为神经元放电活动无损免标记检测技术和光相位成像技术的研究提供一定的基础。