Gd-EOB-DTPA联合多模态MR成像新技术评价ALPPS术后肝脏增生能力及其机制研究

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been described as a promising strategy to induce a rapid and marked increase in future liver remnant volumn. But the mechanism of regeneration, the hepatic functional reserve, and its application in the background of chronic liver disease remain controversial. Previous researches indicated that Gd-EOB-DTPA-enhanced MRI with T1-mapping sequence, diffusion kurtosis imaging, and whole-liver perfusion reflected the states of hepatocellular function, liver diffusion and microcirculation respectively. In addition, the enhancement effect of liver parenchyma on hepatobiliary phase by Gd-EOB-DTPA correlated with the expressions of organic anion transporting polypeptide (OATP) and multidrug resistance associated protein (MRP). Thus, we propose that the MR imaging technologies above will become critical tools for evaluation of ALPPS. In this study, we suppose to evaluate the new multiparameter MR imaging technologies above on the ALPPS rat models, and compare ALPPS with the traditional portal vein ligation and/or bile duct ligation, to assess their diagnostic values in the evaluation of liver regeneration and functional compensation after ALPPS; and further investigate the microstructure basis and mechanisms of liver regeneration, as well as their relationship with the membrane transporters, so as to provide evidence for clinical practice.

联合肝脏离断和门静脉结扎的二步肝切除术（ALPPS）作为一种新兴手术方式能促进残肝快速增生，但肝脏增生机制、肝功能代偿能力、及其在慢性肝病患者中的应用尚存争议。我们前期研究表明，Gd-EOB-DTPA增强T1-mapping成像、扩散峰度成像及全肝动态增强灌注成像可分别反映肝细胞功能、肝内微观弥散及微循环灌注状态；而Gd-EOB-DTPA增强肝胆特异期成像与肝细胞膜有机阴离子转运肽（OATP）及多药耐药蛋白（MRP）密切相关。我们认为，上述MR成像新技术有望成为ALPPS的重要评估工具。本课题将建立大鼠ALPPS模型，并与传统PVL及PVL+BDL术比较，评估上述多模态MR成像新技术对ALPPS术后残肝增生及功能代偿能力的诊断价值，阐明ALPPS可行性及安全性评估的MR关键技术；从多层面探讨肝脏增生的微观结构基础和潜在机制，及其与转运蛋白表达间相关性，指导临床实践。

联合肝脏离断和门静脉结扎的二步肝切除术（ALPPS）作为一种新兴手术方式能促进残肝快速增生，但肝脏增生机制、肝功能代偿能力尚未明确。本项目建立大鼠ALPPS模型，并与传统门静脉结扎术（PVL）比较，评估Gd-EOB-DTPA增强T1-mapping成像、扩散峰度成像（DKI）联合直方图分析等多模态MR成像新技术对ALPPS术后残肝增生及功能代偿能力的评估价值。.本项目证实，ALPPS术后残肝体积增生显著高于PVL术（P=0.0017）。Gd-EOB-DTPA增强MR肝胆特异期T1-mapping成像可有效评价ALPPS术后残肝功能状态，但ALPPS组、PVL组及正常对照组间T1值的下降率（ΔT1%）、OATP1和MRP2 -mRNA表达量间均无统计学差异（P>0.05）。我们认为，ALPPS虽较PVL可快速增加残肝体积，但并不能进一步提高有效残肝功能。.DKI成像结果显示，ALPPS、PVL及正常对照组间D、K、ADC值均存在明显差异（P<0.05），ADC值与增殖指数Ki-67及HGF间呈显著负相关（r=−0.484及r=−0.537, P<0.05），但DKI指数与增殖指数间无显著相关性。因而DKI成像可有效评估ALPPS术后肝脏增生，但其诊断价值不优于传统DWI成像。进一步进行DKI直方图分析显示，ALPPS组D值-均数、中位数、5th/25th/50th/75th百分位数范围低于对照组（P=0.001-0.022），K值-偏度、75th/95th百分位数范围高于PVL组（P=0.011-0.042），ADC值直方图参数在三组间不存在统计学差异；D值-均数、中位数、5th/25th/50th百分数范围，K图-5th百分位数范围与肝细胞大小呈显著相关性（r=-0.582~ -0.426），ADC值直方图参数未见明确相关性。因此DKI直方图分析评估肝脏增生可较常规单指数扩散成像提供更丰富信息，反映其内在微观结构基础。.综上，本项目得出，ALPPS术后残肝显著增生，优于PVL。明确了Gd-EOB-DTPA增强MR肝胆特异期T1-mapping成像、DKI成像联合直方图分析对ALPPS术后肝脏增生及功能代偿能力的诊断价值，阐明了ALPPS可行性及安全性评估的MR关键技术；初步揭示了ALPPS术后肝细胞功能状态、微观弥散效应，及肝组织增生的微观结构基础及潜在机制。