基于同步辐射相衬成像的肝泡状棘球蚴病微观病理形态学研究

Hepatic alveolar echinococcosis (HAE) is characterized by high mortality rate, similar to malignant tumor, and mainly detected and diagnosed with ultrasound, CT, and MRI techniques. Although having their own features and advantages, these techniques can only reach the resolution of sub-centimeter level, and have technical bottlenecks for realization of 3D, high resolution, non-destructive examination. Although electron microscope, on the basis of micro-level sample slice, can achieve quasi nanoscale observation, it cannot meet the need of the 3D in-suit, even for in-vivo, biomedical non-destruction studies. In our project, we combine the advanced synchrotron-based high-resolution X-ray phase contrast imaging technique with the HAE experimental rat models and human postoperative specimens to carry out the research of the pathological micro-structures and their morphological development of HAE with different stages, and the comparison study of morphological structural changes before and after feeding drugs, which will make us obtain the morphological data of HAE different pathological periods, including in-suit micro-structural features, 3D microvascular vessel networks, biological 3D boundary determination, drug therapy, etc. It is helpful to explore the microscopic and dynamic HAE pathomechanism and the evaluation basis of biological activity, and has practical significance for revealing the rule of AE pathological occurrence and development and the relationship between structure and function. It has great potential for providing new methods of HAE early clinical diagnosis.

肝泡状棘球蚴病（HAE）具有类似恶性肿瘤的特点，病死率高，主要采用超声，CT，核磁（MRI）进行检测和临床诊断，各具特点和优势，但都属于亚厘米级的分辨检测，对实现早期AE病变的三维高分辨原位无损检测尚存在技术瓶颈。虽然，电镜可以实现准纳米级的切片观测，但是需要切割样品到微米级水平，无法实现三维原位乃至活体研究。本项目利用基于同步辐射的高分辨X射线相位衬度成像技术，采用HAE实验性SD大鼠模型和人体术后标本，开展HAE的微米级活体原位结构和不同时期病理发生发展的形态变化的实验研究，以及喂药前后实验性动物模型的病理结构变化的对照研究，从而获取不同病理时期HAE形态结构特征，三维微血管网络分布，生物学微观立体边界确定，药物治疗等方面的微结构形态学数据。探索HAE微观动态病理机制和生物活性形态学评价依据，对揭示病理的发生发展规律及结构功能作用关系具有重要的现实意义，为HAE早期临床诊断提供新思路。

肝泡状棘球蚴病（HAE）具有类似恶性肿瘤的特点，病死率高，主要采用超声，CT，核磁（MRI）进行检测和临床诊断，各具特点和优势，但都属于亚厘米级的分辨检测，对实现早期HAE病变的三维高分辨原位无损检测尚存在技术瓶颈。虽然，电镜可以实现准纳米级的切片观测，但是需要切割样品到微米级水平，无法实现三维原位乃至活体研究。本项目利用同步辐射高分辨X射线相位衬度成像技术，采用HAE实验性SD大鼠模型和人体术后标本，开展了HAE的三维微米级原位结构和不同时期病理发生发展形态变化的实验研究，以及喂药前后实验性动物模型的病理结构变化的对照研究，从而获取不同病理时期HAE形态学特征、微血管树分布、生物学浸润体边界、药物治疗评价等方面的微观病理形态学数据。通过上述研究，开发了基于相移吸收二元性（PAD）相位恢复算法、软组织实验参数优化、图像分割算法、光栅成像等改进型相衬成像技术，为研究HAE微观病理形态学和早期诊断提供了重要技术保障和多尺度全周期数据支持。其微米级三维无损影像数据，对揭示HAE病理机制和抗HAE药效直观评价具有重要的临床意义，为HAE早期诊疗和新药物评价提供一种全新的三维、原位、无损显微定量的新技术，并可推广应用到软组织肿瘤、心脑血管、神经网络等生理病理领域。