基于高灵敏超极化13C MRI的肝细胞癌的动态演化研究

Hepatocellular carcinoma (HCC) is a kind of primary liver cancer with high mortality and its dynamic evolution mechanism has always been a hot and difficulty topic. Currently, commonly used HCC imaging methods are based on magnetic resonance imaging (MRI) technology, but MRI has limited sensitivity at the molecular level. Therefore, this project develops high-sensitivity hyperpolarized 13C MRI to visualize the dynamic evolution of HCC in vitro and in vivo. The main research contents are as follows: 1) based on dynamic nuclear polarization (DNP) theoretical model, a DNP device is built and then four hyperpolarized 13C probes are prepared; 2) based on a vascularized solid HCC chip, by combining hyperpolarized 13C micro-MRI and optic imaging technologies, the changes in metabolic microenvironment and in tissue structure and function during the evolution of HCC are visualized in vitro; 3) based on the mouse HCC model, the metabolic microenvironment changes during the evolution of HCC are visualized in vivo and the relationship between metabolic characteristics and histopathology is analyzed using high-sensitivity hyperpolarized 13C MRI. This project has important theoretical significance and application value for exploring the evolution mechanism of HCC, developing the early diagnosis methods of HCC, and developing the therapeutic drugs for HCC.

肝细胞癌（HCC）是一种高死亡率的原发性肝癌，其动态演化机制一直是研究的热点和难点。目前常用的HCC影像学方法基于磁共振成像（MRI）技术，但是MRI在分子水平上灵敏度有限。据此，本项目拟发展高灵敏超极化13C MRI成像技术，从体外、体内两方面可视化研究HCC的动态演化过程。主要研究内容为：1）基于动态核极化（DNP）理论模型，搭建DNP装置，制备四种超极化13C探针；2）基于血管化实体HCC芯片，联合超极化13C micro-MRI技术和光学成像技术，体外可视化研究HCC演化中的代谢微环境变化及组织结构和功能变化；3）基于小鼠HCC模型，利用高灵敏超极化13C MRI成像技术，体内可视化HCC演化中的代谢微环境变化并分析代谢特征与组织病理的关系。本项目的成功开展对探索HCC动态演化机制、发展HCC早期诊断方法以及研发HCC治疗药物具有重要的理论和应用价值。

肝细胞癌是一种高死亡率的原发性肝癌。目前常用的肿瘤影像学方法基于磁共振成像（MRI）技术，但是MRI在分子水平上灵敏度有限。据此，本项目搭建了氮-空位（NV）色心金刚石超极化装置，研制了高灵敏13C多核磁共振成像系统，从体外、体内两方面可视化研究肿瘤的动态演化过程。主要研究内容为：1）基于动态核极化（DNP）理论模型，搭建DNP装置；2）研制多核成像系统及开发多核成像序列；3）构建血管化实体肝癌芯片，实现原位肝癌的生长监测以及肝肿瘤影响肝内血管网络与氧环境的研究；4）构建多功能纳米诊疗探针，基于小鼠肿瘤模型，评估了纳米探针的成像性能及肿瘤治疗效果。本项目的成功开展对探索肝细胞癌动态演化机制、发展肿瘤早期诊断方法以及研发肿瘤治疗药物具有重要的理论和应用价值。