多参数MRI对慢性胰腺炎纤维化中EMT的监测及疗效评估研究

Chronic pancreatitis (CP) is a clinical refractory disease, and the incidence of pancreatic cancer in CP patients was significantly higher than that in the normal population. The most typical histopathological feature of CP is pancreatic fibrosis, which closely related to the activation of pancreatic stellate cells (PSCs). The knowledge that PSC activation involves an EMT process could be implied to blocking the activation of PSCs by inhibiting the process of EMT in targeted treatment of CP. In this preliminary study, the correlation were analysed between the imaging parameters of non enhanced (IVIM-DWI, DKI) and enhanced (DCE-MRI) MR functional imaging and typical epithelial and mesenchymal marker expression in EMT of CP cat pancreatic fibrosis. Furthermore, non enhanced MRI was compared with enhanced value functional imaging for evaluation of CP cat pancreatic fibrosis EMT. In conclusion, we aim to find out the related parameters of multi-parameter MR imaging as noninvasive biomarkers to detect EMT in pancreatic fibrosis and monitor and assess targeted therapy in EMT of CP pancreatic fibrosis.

慢性胰腺炎（CP）是一种临床难治性疾病，且CP患者较正常人群的胰腺癌发病率明显增高，CP的主要病理特征是胰腺纤维化，其与胰腺星形细胞（PSCs）的活化密切相关。在PSCs这一过程中，发生了上皮间质转化(EMT)的改变，有望通过抑制EMT过程阻断PSCs的激活来靶向治疗慢性胰腺炎。但尚无非侵入性的检查方法来监测和评估胰腺纤维化中的EMT的报道。本研究拟在CP猫胰腺纤维化模型通过非增强（IVIM-DWI、DKI）及增强（DCE-MRI）参数MR功能成像获得相关参数，将这些影像学参数与CP猫胰腺纤维化EMT中的典型上皮及间质标志物的表达进行相关性分析，并对比非增强及增强MR功能成像对CP猫胰腺纤维化EMT的评估价值。探索MR多参数成像的相关参数作为非创伤性的生物标记物来检测CP胰腺纤维化中EMT及监测和评估CP胰腺纤维化的EMT靶向治疗的疗效。

慢性胰腺炎（CP）是一种临床难治性疾病，且CP患者较正常人群的胰腺癌发病率明显增高，CP的主要病理特征是胰腺纤维化，其与胰腺星形细胞（PSCs）的活化密切相关。在PSCs这一过程中，发生了上皮间质转化(EMT)的改变，有望通过抑制EMT过程阻断PSCs的激活来靶向治疗慢性胰腺炎。但尚无非侵入性的检查方法来监测和评估胰腺纤维化中的EMT的报道。本研究显示了11.7T 超高场强MRI能够清晰地显示大鼠胰腺的位置和轮廓，可用于啮齿类动物胰腺的临床前研究。IVIM 、DKI和DCE-MRI 是研究胰腺疾病的一种有用的非侵入性成像技术，其扩散参数（ADC, D, MD, MK）与灌注参数(Ktrans、Vp)具有较好的可重复性。这些扩散参数与灌注参数可用于评估胰腺纤维化分期，同时这些参数也与EMT标记物α-SMA的表达显著相关，其中MK、Ktrans、Vp与E-cadherin表达显著相关。但非增强与增强MR成像及两者联合对CP大鼠胰腺纤维化EMT的评估效能无明显差异。此外，MR多参数成像的相关参数有望作为非创伤性的生物标记物来监测和评估CP胰腺纤维化的EMT靶向治疗的疗效。