磁共振功能成像预测慢性病毒性肝炎门静脉高压症的实验及临床研究

Portal vein hypertension is often associated with the most severe clinical syndromes of liver diseases.Assessing the extent of portal hypertension is very meaningful for detecting of the associated diseases, predicting bleeding and monitoring the clinical precedure. Portal pressure begins to increase in liver fibrosis S2, and is often found only when clinical signs of decompensated cirrhosis emerges. Hence, There is a lack of safe and noninvasive way for forecasting and early diagnosing protal hypertension. In our last project, we found the relationship among liver fibrosis , stiffness of liver and spleen, and portal vein hypertension syndromes.In this project, we plan to explore the relationship between the portal hypertension, liver and spleen elasticity measured by MRE (magnetic resonance elastography) and perfusion parameters by perfusion weighted imaging (PWI) in both the animal models and clinical cases; initially establish the portal pressure mathematical model and evaluate whether it works well or not; histological, serological and virological results were also observed to see the changes along with portal pressure changes and the process of liver fibrosis, to figure out the cut-off points of the esophageal varices and bleeding, to clarify pathophysiology mechanisms and to find the key steps of when the portal pressure was decompensated and portal hypertension starts.

门静脉高压症常与最严重的临床肝病症候群相关，预测及评估门静脉压力升高的程度，对检测病情发展、预测出血及评价预后意义深刻。门脉压力在肝纤维化S2期即开始升高，而临床常在肝硬化失代偿期才发现相关征象。临床缺乏安全无创、可行性强的门脉高压预测和预警方法。本研究在上一肝纤维化课题中发现，肝、脾弹性值与门脉高压症候群密切相关，拟在本课题中综合运用磁共振弹性成像（MRE）及全肝灌注成像（PWI），结合窦性门脉高压动物模型（有创性获得金标准门脉压力梯度值）及大样本临床病例, 利用肝、脾病理生理改变的相对关系，观察MRE所测肝、脾弹性值及PWI所得灌注指标与门脉压力的相关性; 初步建立门脉压力定量的数学模型, 反馈、验证其有效性；比照组织学、血清学及病毒学结果，确立门脉高压、食管胃底静脉曲张及出血的截点预测值; 阐明病理生理变化机制，找出门脉压力调节及失代偿的关键因素及启动阶段。

门静脉高压症常与临床最严重的肝病症候群密切相关，预测及评估门静脉压力升高的程度，对监测肝病进展、预测食管胃底静脉曲张及出血程度意义深刻。本课题秉承既往的多项慢性肝病、肝纤维化的课题研究成果，应用动物模型结合临床实验，采用多模态磁共振功能 成像对肝纤维化进行综合评估，深入探讨了门脉压力与肝纤维化的变化规律，并发现了安全无创、可行性强的门脉高压预测和预警方法。本课题取得成果如下：（1）在中国大陆地区使用弹性成像MRE超过10年，慢性肝病及肝硬化患者随访队列数量超过千例，与MRE发源地—美国梅奥医疗中心（Mayo Clinic）签署长期合作关系（2013年至今）；（2）发现肝、脾弹性值与门脉高压症候群密切相关，综合运用磁共振弹性成像（MRE）及弥散成像技术（如IVIM）；利用肝、脾病理生理改变的相对关系，成功建立门脉压力定量的模型, 并验证了其有效性；（3）比照有创性门静脉压力梯度HPVG检查，组织学、血清学及病毒学结果，发现在肝脏纤维化进展期即逐渐出现脾大及门脉压力增大的征象，脾脏硬度值是肝硬化食管胃底静脉曲张破裂出血的独立危险因素，与HPVG所测门脉压力密切相关；（5）项目申请者“肝纤维化无创性诊断标准的确立与临床应用”获得辽宁省科技进步一等奖（第二）、辽宁省医学科技一等奖（第二），中华医学科技奖三等奖（第二），本课题研究内容均占有重要地位。课题期间本研究共发表标注论文约17篇，其中SCI 文章5篇，最高单篇文章影响因子为9.566，中文核心期刊杂志12篇。