正常/脑缺血时皮层扩散性抑制三维传播模式的光声成像方法研究

Cortical spreading depression（CSD） is a neurophysiological phenomenon which occurs repeatedly in many neural disorders.The research of the initiation and propagation of CSD will facilitate the disclosure of the mechanisms of these neural disorders. Also, the model of CSD will be useful in the development of curing method of the neural disorders and drug discovery. However, due to the limitation of the imaging instruments, the researches of the CSD mainly focus on the two-dimensional observation methods for the propagation of CSD in the surface of the cortex. In this research, we propose a method to in-vivo observe the propagation of the CSD in three-dimension with photoacoustic microscopy. To acquire the hemodynamic changes and the neuronal electric activities simultaneously, we introduced the voltage-sensitive dyes. We also use optical clearing technique to increase the signal-to-noise ratio of the imaging. We will establish the method to analyse the image acquired with photoacoustic microscopy to characterize the propagation of CSD in normal state and cerebral ischemia. And consequently acquire the rule of the three-dimensional propagation of CSD in cortex in-vivo. This research will provide a three-dimensional high-resolution method for in-vivo investigation of the propagation of CSD. It will be also helpful in the understanding of the rule and mechanism of propagation of CSD.

皮层扩散性抑制（CSD）是一种在多种神经系统疾病发生时会反复出现的现象，对CSD产生和传播模式的研究有助于探究神经系统疾病的发生发展机理，构建CSD模型有助于这些疾病治疗方法的研究和药物的开发。目前受成像仪器的限制，对CSD的在体高分辨率成像仅局限于对皮层表面进行二维传播模式的研究。因此，本项目拟通过研究适用于在体的三维动态观测CSD传播的光声显微成像方法；并结合光透明技术以便提高成像信噪比，结合电压敏感染料以同时观测CSD在脑皮层内三维传播时的血液动力学参数与皮层神经元电活动；建立光声信号表征CSD传播的分析方法。以正常状态下和脑缺血状态下的动物模型为实验对象，获取CSD在三维空间动态传播的时空规律。本项目的研究将为在体CSD三维传播模式提供高分辨率的研究方法，有助于更加深入地理解CSD在皮层中的传播规律与传播机制。

皮层扩散性抑制（CSD）是一种在多种神经系统疾病发生时会反复出现的现象，对CSD 产生和传播模式的研究有助于探究神经系统疾病的发生发展机理，构建CSD 模型有助 于这些疾病治疗方法的研究和药物的开发。目前受成像仪器的限制，对CSD 的在体高分辨率成像仅局限于对皮层表面进行二维传播模式的研究。因此，本项目研究了高分辨率、高信噪比的快速光声显微成像方法，提出并实现了基于反射式物镜的光学分辨光声显微成像系统，在580 nm激光波长成像深度能够达到0.9 mm，并能获得高的在焦侧向横向分辨率为1.2 μm。利用光透明剂降低组织的光散射系数，明显提升光声成像在深层组织中的成像性能，进一步我们将光声成像与超声成像结合，率先实现了动态监测皮肤组织光透明过程中的声学参数与光学参数的变化过程。并将颅骨光透明技术引入光声成像中，显著提升了皮层血管光声成像的信噪比。