人体肝脏功能单元的计算机三维重建研究

Liver is one of the most important metabolic organs in human body. Liver diseases, such as hepatitis, liver cirrhosis, liver cancer and hepatonecrosis, could be fatal if liver failure occurs. Currently, liver transplantation is the main therapy for liver failure . However, due to lack of donor organs, bioartificial livers, especially those printed by three-dimensional (3D) bio-printing technology are considered as a substitute. Till now, a number of studies have performed 3D printing of living liver cells, but just focused on technologies of cell culture and printing. A 3D model of liver functional unit still remains to be built. In order to be a functional liver, liver cells must be arranged in a scientific and orderly manner according to the specific 3D construction principle of liver tissues to form 3D structures of human liver, and to establish a particular 3D connection with blood vessels, bile duct and connective tissues so as to constitute basic functional units. Therefore, the primary task of 3D printing of liver is to construct a 3D model of liver functional unit. On the basis of our previous studies on digital human, this project is intended to construct a 3D digital model of functional unit of human liver using serial tissue section and 3D reconstruction, so as to promote 3D printing of liver.

肝脏是人体最重要的代谢器官之一，肝炎、肝硬化、肝癌等疾病发展到肝功能衰竭时将直接危及生命，肝移植成为此时治疗的主要手段。然而，由于供体来源匮乏，人们只好寄希望于生物人工肝，特别是采用生物3D打印技术打印活的肝细胞，以期用3D打印肝脏替代人体肝脏。基于这一设想，已有不少关于肝活细胞3D打印的研究，但均限于细胞培养和细胞打印的技术研究，尚缺乏用于细胞打印的肝脏功能单元计算机三维模型。要使肝脏正常行使功能，肝细胞必须按照肝脏组织特定的三维空间细胞构筑规律科学有序地排列，形成特定的人体肝脏组织三维空间结构，包括和血管、胆管、结缔组织之间的立体空间关系，构成基本的功能单元。因此，建立肝脏功能单元的三维结构模型，是进行肝脏器官打印的首要工作。本课题拟在本课题组已有的数字化人体研究工作基础上，采用连续组织切片和细胞三维重建方法，建立肝脏功能单元的计算机三维模型，为肝脏的3D打印提供首要的计算机模型。

肝脏由于供体来源匮乏，人们只好寄希望于生物人工肝，特别是采用生物3D打印技术打印活的肝细胞，因此亟需细胞打印的肝脏功能单元计算机三维模型。我们已经完成了3例HE肝组织染色连续切片数据集和3例fMost肝组织数据集的采集，HE染色数据集已经进行了图像配准，完成了连续断层组织图像数据库的构建；我们分割构建了肝功能单元，包括肝小叶、肝细胞索、肝血窦、小叶间动脉、小叶间静脉、小叶间胆管、中央静脉、小叶下静脉的三维数字化模型，并进行了各项三维形态学参数包括肝小叶长轴长度、肝小叶体积、肝小叶表面积、肝小叶平均直径/肝小叶长度、中央静脉长度、中央静脉长度/肝小叶长轴长度等的测量，发现：1. 肝小叶外轮廓为不规则的较圆钝的多边形结构，边长不等，而且肝小叶外形大小不一、高矮不一、胖瘦不一；2. 肝小叶的中央静脉并不位于肝小叶正中，有多个属支；3. 肝血窦为相互交织的血管网，并不构成放射状排列:4. 汇于肝静脉系统的小叶下静脉和来自于Glisson系统的小叶间动脉、静脉和胆管分别位于肝小叶的两极，管道独立走形。研究发现更新了传统的教材和组织学图谱。