肝纤维化是各种慢性肝病进展至肝硬化的必经阶段，早期、准确评估纤维化程度具有重要临床意义，目前尚缺乏公认可靠的无创评估手段。前期研究表明，Gd-EOB-DTPA增强肝胆特异期T1-mapping成像、双指数弥散成像、全肝动态增强灌注成像和磁敏感成像可分别反映肝细胞功能损伤，肝内微观弥散、微循环灌注，及铁沉积状态；而Gd-EOB-DTPA增强肝胆特异期成像与细胞膜有机转运肽（OATP）和多药耐药蛋白（MRP）密切相关，肝纤维化可引起OATP和MRP表达水平改变，导致肝实质T1弛豫时间的改变。我们认为，上述MR成像新技术有望成为肝纤维化的重要诊断和评估工具。本课题将采用三种大鼠肝纤维化模型及HBV相关肝纤维化患者，对上述多模态MR成像新技术中相关影像生物标志物进行测定比较，并对细胞膜转运蛋白表达水平及活性进行相关性分析，从多层面探讨肝纤维化的发生发展机制及其分级诊断、疗效评估价值，指导临床实践。

Liver fibrosis is an inevitable stage to cirrhosis in response to repetitive liver injury from various causes, early and accurate assessment of liver fibrosis plays an important role in clinical work. But until now, there are still no acknowledged noninvasive approaches in fibrosis assessment. Gd-EOB-DTPA-enhanced MRI with T1-mapping sequence, intravoxel incoherent motion imaging, whole-liver perfusion and susceptibility weighted Imaging reflect the states of hepatocellular impairment, liver diffusion and microcirculation, as well as iron deposition respectively. In addition, the enhancement effect of liver parenchyma on hepatobiliary phase by Gd-EOB-DTPA correlates with the expressions of organic anion transporting polypeptide (OATP) and multidrug resistance associated protein (MRP), and liver fibrosis can alter the levels of OATP and MRP, which result in differences in T1 relaxation time of liver parenchyma. Thus, we propose that the MR imaging technologies above will become critical tools for diagnosis and evaluation of liver fibrosis. In this study, we suppose to measure varied imaging biomarkers of the new multiparameter MR imaging technologies above on three different rat fibrosis models as well as pathologically confirmed patients with HBV-related liver fibrosis, so as to assess their values in hierarchical diagnosis and therapeutic evaluation of liver fibrosis and their relationship with the membrane transporters (OATP, MRP), and further investigate the mechanisms of liver fibrosis.