SD大鼠肝癌模型的动态量化7.0T磁共振功能成像与相关微小RNAs改变机制的研究

The purpose of this study was to investigate the feasibility of using 7.0-T Magnetic Resonance Imaging scanner as a quantitative multi-parametric technique for the diagnosis of hepatocellular carcinoma (HCC) in a modified SD rat model induction with Diethylnitrosamine and mechanism of miR-21、miR-122、miR-199. From regenerative nodules (RN),dysplastic nodules (DN) to early HCCs,high resolution diffusion weighted imaging(DWI) and Magnetic resonance elastography (MRE) were performed,and observe the changes of miRNA and histologic examination during the dynamical process. We would compare the MRI' measurements of each type of hepatic nodule,confirme at quantitative histopathology.According to the pathologic characteristics and quantitative measurements,analysis the results and influences of liver fibrosis and vascular-reaction.Sensitivity and specificity of quantitative measurements of functional MRI would be calculated.To clarify progressing mechanisms of rat model evolvements and functional MRI diagnostic theory,in an attempt to forecast biologic characteristics of rat model with dynamic functional MRI and quantitative multi-parametric analysis. Our final aim was to provide early functional MRI diagnoses of human precancerous lesion,and a new hypothesis to clinical therapy.

由二乙基亚硝胺诱发的大鼠肝癌模型具备与人类肝细胞癌相似的肝硬化及肝炎背景，能够较移植型肝癌模型，更接近人类肝细胞癌的肿瘤生物学改变。本研究对诱发SD大鼠肝癌模型，从肝硬化、发育不良结节到癌变的动态过程，进行量化超高场7.0T磁共振功能成像（高清弥散成像及弹性成像），并对比高场3.0T磁共振功能成像,研究量化磁共振弥散及弹性成像规律,检测模型miR-21、miR-122、 miR-199的动态表达，对照HE染色、肝纤维化MASSON染色及肿瘤血管生成, 分析肝硬化期、癌变期磁共振功能影像和分子生物学及病理改变特征，总结超高场磁共振功能成像量化指标的动态改变和各时期病理及分子生物学变化的相关性和规律性，阐明SD大鼠肝细胞癌演变机制和功能成像的量化诊断依据，期望通过磁共振功能成像动态量化指标及相关miRNA动态改变，预测模型的肿瘤生物学改变，为人类肝细胞癌癌前病变的早期诊断提供新的理论依据。

本研究对诱发SD大鼠肝癌模型，从肝硬化、发育不良结节到癌变的动态过程，进行了量化超高场7.0T磁共振功能成像，并对比高场3.0T磁共振功能成像，并且研究了量化磁共振扩散及灌注成像规律，检测模型miRNA的动态表达水平作为肝细胞癌分子生物学改变检测标志物的可行性，对照HE染色、肝纤维化MASSON染色及肿瘤血管生成, 分析肝硬化期、癌变期磁共振功能影像和分子生物学及病理改变特征，总结超高场磁共振功能成像量化指标的动态改变和各时期病理及分子生物学变化的相关性和规律性，阐明SD大鼠肝细胞癌演变机制和功能成像的量化诊断依据，通过磁共振功能成像动态量化指标及相关miRNA动态改变，预测模型的肿瘤生物学改变，为人类肝细胞癌癌前病变的早期诊断提供新的理论依据。