光片显微成像（Light Sheet Microscopy, LSM）是新兴的三维荧光成像技术，可对小鼠器官进行高分辨率观测。2014年新出现的全身透明化技术为LSM进行小鼠全身成像带来了曙光，但也带来新的挑战性难题，LSM只能观测小鼠体内被标记组织的荧光信息，无法全面反映小鼠的完整信息；小鼠内部复杂组织使LSM产生严重的条纹伪影，极大破坏了小鼠全身成像的质量。针对这些新问题，本项目拟研制螺旋光学投影成像（螺旋OPT）和LSM的融合系统，利用螺旋OPT非荧光信息与LSM荧光信息互补，并研发基于微分同胚性多尺度模型的关键配准技术；利用螺旋OPT图像构建条纹预测模型，辅助LSM进行条纹伪影校正；开展内皮特异性细胞黏附分子CD146基因敲除小鼠的全身血管成像，定量评估CD146在小鼠全身血管网络生成中的作用。本项目研究新的融合显微成像系统和技术，并应用于小鼠全身血管成像，具有重要预临床应用价值。

Light sheet microscopy (LSM) is an emerging 3D fluorescent imaging technique, which is used for high resolution imaging of mouse organs. The newly developed whole mouse clearing method in 2014 brings dawn to whole mouse LSM imaging. However, it also brings challenging problems for LSM. LSM can only observe fluorescent signal which is not enough for whole mouse imaging. Moreover, serious stripe artifacts caused by complex structures of the mouse will deteriorate the LSM image quality. To solve these problems, we will build a hybrid helical optical projection tomography (helical-OPT) and LSM system to complement LSM’s fluorescent signal with helical-OPT’s non-fluorescent signal. Moreover we will develop a novel image registration method for helical-OPT and LSM by using of multi-scale diffeomorphism model. Furthermore, we will construct a prediction model for stripe artifacts based on helical-OPT images. This model will be used to reduce the stripe artifacts in LSM images. Finally, we will apply our multimodality microscopy system to observe the blood vessel network in endothelial-specific CD146 knock-out mice. We want to quantitatively explore the role of CD146 in whole mouse angiogenesis. In this project, we research on novel multimodality microscopy technique and apply it to whole mouse blood vessel network. Our research possesses a great value of preclinical application.