肝细胞癌乙酸盐PET动态显像的动力学分析及临床应用研究

Hepatocellular carcinoma(HCC) is one of high-incidence cancers in China. Early diagnosis is critical for patients’ survival. However, it is reported that 30%-50% of primary HCC are missed in FDG PET/CT imaging. Carbon-11 can work as well complement to FDG in the detection of HCC. In 2009, we found that dual-time point PET/CT imaging with carbon-11 acetate (C-11 AC) could provide more valuable information for differentiated diagnosis FNH from HCC than routine single C-11 AC PET/CT imaging, which had not been reported before in literatures. This preliminary finding indicates that there may be some unknown clues which have been omitted in routine single time PET/CT imaging which perhaps is valuable to the differential diagnosis of liver masses. .Our research is to find whether serial PET/CT images can demonstrate critical and additional information to HCC diagnosis. We hope to set up mathematic models for data and image analysis in addition to visual identification, which will give optimal and rational quantification for final diagnosis. .To carry out the differentiated diagnosis, this program will focus more on several key issues，such as (1) A scheme in respect of reconstruction time interval will be put forward to extract more tracer information, and to reduce the noise of the image simultaneously. (2) Reducing respiration artifacts. (3)The selection of fitting model. (3) The proportion of the blood supply in the liver masses and the relationship with metabolic abnormal will be computed. (4) Pathological result is regarded as the gold standard to verify the protocols and models. (5) We will also compare the results with those got from other modalities, such as CT and MRI..Focusing on the early diagnosis of HCC with 11C-AC dynamic PET imaging, we will inventively reveal the characteristics of the HCC by combining the variation in blood supply proportion with abnormality in fatty acid metabolism. A complete system analyzing the PET/CT dynamic data will be built up firstly in our country. This program would be of high effectiveness on exploring the clinic indicator used for HCC diagnosis with dynamic PET/CT, piercing through the routine method reflecting metabolic feature on single time PET/CT imaging. And the result of this program will also aid in the research of relative field, such as PET/MR and new tracer application research.

利用碳-11 乙酸盐（C-11 AC）在肝细胞癌（HCC）诊断中的优势特性，通过动态显像方法系列观察示踪剂在肿瘤内的变化过程，在解决呼吸运动对病灶定量分析影响基础上，建立更加完善HCC动力学模型和定量分析方法，量化整个变化过程，寻求HCC动脉血供、代谢异常及二者之间关系的变化规律，突出动态HCC显像分析的临床特异性指标，辅助临床进行HCC鉴别诊断，突破目前PET/CT单个时间点反映肿瘤代谢特点常规思路。. 构建 PET/CT 肝肿瘤数学研究框架，包括时间采样方案、呼吸伪影校正、输入输出活度曲线提取及拟合、肝肿瘤双血供房室模型确立、血流/代谢参数计算、参数图像/曲线的形成以及相关的统计分析，改善目前临床核医学影像诊断依靠视觉和简单定量分析的现状，框架式课题研究成果在新型显像剂机理探讨、PET/MR肿瘤研究等转化医学领域具有延展性。

原发性肝癌（hepatocellular carcinoma，HCC）是我国的高发肿瘤之一，早期诊断对提高肿瘤治愈率起到至关重要的作用。在前期研究中发现利用11碳-乙酸盐（11C-AC）PET动态显像能够辅助HCC的良恶性诊断。.本课题首先对比了滤波反投影、有序子集期望最大化、使用飞行时间的有序子集期望最大化及使用飞行时间和点扩散函数的有序子集期望最大重建方法对运动器官的影响，在成像中存在位移的器官上分析了各类重建算法的优劣；研究了不同时相划分对运动伪影消除的影响。其次，在图形化非线性最小二乘法（graphed nonlinear least square，GNLS）的基础上提出了逐像素参数估计方法（pixel based GNLS，PGNLS），该方法在相较传统的GNLS，对噪声不敏感，更适用于PET图像的动力学参数计算。考虑到肝脏是由肝门静脉和肝动脉共同供血的特点，对比了不同肝脏动力学模型对HCC鉴别诊断的能力。结果显示肝门静脉单独供血作为动脉输入函数的模型具有最好的拟合优度，通过拟合得到的时间活度曲线（time activity curve, TAC）更贴近病灶及正常组织的TAC，并且病灶与正常肝脏组织有着更显著的差异。.本研究对肝细胞癌11C-AC PET动态显像的动力学分析进行了方法学的研究，建立了完整的分析流程。通过动力学分析，可以在肿瘤区域观察到更多的细节，增强了不同肿瘤组织间的对比度，为临床上对肝细胞癌的鉴别诊断提供了定量的信息。此外，本课题采用的11C-AC PET动态显像的动力学分析也拓展至其他脏器上的疾病研究，例如：心脏、肺。.课题共发表相关SCI论文8篇（IF = 47.598）；中文核心期刊论著4篇，待发表1篇；待申请专利1项；参加核医学国际会议6次，做大会报告3次，壁报交流7篇；培养博士生2名，硕士研究生6名；与奥地利维也纳总医院以及美国费城儿童医院建立了医学与基础研究合作关系，搭建好较合理的学科交叉的人才队伍，为今后工作开展奠定了坚实基础。本项目作为我科室子项目之一获得2019年北京市科学技术三等奖，成果已在临床推广使用，并开始创造经济效益。