多参数定量MR动态监测胰腺癌化疗中PSCs介导的纤维化及其与疗效关系的实验研究

白蛋白结合型紫杉醇/吉西他滨（NG）是胰腺癌临床一线用药之一，但其疾病控制率约为48%-76.6%。如何准确预测及评估NG化疗疗效，是急需解决的科学问题。大量研究表明肿瘤微环境内胰腺星形细胞（PSCs）介导的纤维化情况与化疗疗效及预后高度相关。既往多参数定量MR在多种腹部肿瘤化疗疗效评估中显示了巨大的应用前景，其中DKI、T1mapping技术可定量纤维化程度，DCE技术则可反应肿瘤微血管灌注情况。两类技术联合有望无创监测NG治疗后肿瘤纤维化改变，进而预测及评估化疗疗效。本研究拟利用大鼠原位胰腺癌模型，获取每次治疗后病理结果，了解治疗过程中PSCs介导的纤维化变化情况，解决常规临床中无法获取病理结果的难题。同时，利用多参数定量MR实时监测每次治疗，获取并分析每次治疗MR定量参数与病理纤维化指标之间相关性，为临床预测及评估NG治疗效果提供无创、实用的方法。

Nab-paclitaxel plus gemcitabine (NG) is one of the first-line clinical therapy for pancreatic cancer, but its disease control rate is around 48%-77.6%. How to accurately predict and evaluate the therapeutic effect of NG chemotherapy is an urgent problem to be solved. Previous studies have proved that PSCs mediated fibrosis in tumor microenvironment is related to chemotherapy efficacy and prognosis. Multi-parameter quantitative MR has shown encouraging results in the evaluation of various tumor therapeutic effects, among which, DKI and T1 mapping can quantify the degree of fibrosis, while DCE can reflect the microvascular perfusion. The combination of the two technologies is expected to be useful in monitoring the changes of fibrosis and tumor microenvironment after NG treatment, and then predict and evaluate the treatment efficacy. The purpose of this study is to use the orthotopic rat model of pancreatic cancer to obtain the pathological results after each treatment, to understand the changes of PSCs mediated fibrosis during the treatment, and to solve the limitations of getting pathology results in clinical practice. At the same time, real-time multi-parameter quantitative MR was used to analyze the correlation between MR quantitative parameters and pathological fibrosis parameters, so as to provide a noninvasive and practical tool for clinical prediction and evaluation of NG treatment effect.