应用MRI动态增强双输入血流动力学模型评价中晚期肝细胞癌微血管特征

Applications of a dual-input pharmacokinetic model of dynamic contrast-enhanced MRI for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma

目的:调查MRI动态增强双输入双室血液动力学模型评价中晚期肝细胞癌肿瘤微血管特征的可行性。方法:自2014年1月至2015年4月间对28例肝细胞癌(HCC)患者的血流动力学参数(K_(trans)、F_p、PS、K_(ep)、V_e、V_p、HPI)使用双输入双室血流动力学模型(双输入extended Tofts和双输入双室exchange模型)进行测量和分析。使用配对Student’s t检验和非参数配对Wilcoxon秩和检验比较2种模型测量的相同的几个血流动力学参数;使用pearson相关性分析观察这些相同的参数有无相关性。使用pearson分析肿瘤大小和血流动力学的参数,而HCC分期、大小和血流动力学参数的相关性使用spearman相关性分析。结果:在双输入双室exchange模型(2CXM),F_p值明显大于PS值[F_p=1.07 m L/(m L·min),PS=0.19 m L/(m L·min)]。HPI在双输入extended Tofts模型和双输入2CXM分别为0.66和0.63。在2种模型中,K_(ep)、V_p和HPI差异无统计学意义(P=0.524,P=0.569,P=0.622)。除了V_e,2种模型中所有的血流动力学参数都具有相关性。双输入2CXM模型中的F_p和PS与双输入extended Tofts模型的K_(trans)相关(r=0.566,P=0.002;r=0.570,P=0.002),K_(ep)、V_p和HPI在2种模型中显正相关(r=0.594,P=0.001;r=0.686,P=0.0001;r=0.391,P=0.004)。双输入extended Tofts模型的V_e显著小于双输入2CXM模型中的V_e值(P=0.004)且两者无相关性(r=0.276,P=0.156)。无论是肿瘤大小和分期都未与血流动力学参数相关(P>0.05)。结论:双输入双室血流动力学模型可以评价中晚期HCC的微血管病理生理特征。双输入extended Tofts模型对于测量V_e更稳定,然而双输入2CXM对测量微血管渗透性可能更详细和准确。

Objective： To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma （HCC）. Methods： From January 2014 to April 2015, pharmacokinetic parameters included transfer constant （Ktraues）, plasma flow （Fp）, permeability surface area product （PS）, efflux rate constant （Kep）, extravascular extracellular space volume ratio （Ve）, blood plasma volume ratio （Vp）, and hepatic perfusion index （HPI） were prospectively measured and analyzed using dual-input two-compartment tracer kinetic models included a dual-input extended Torts model and a dualinput 2-compartment exchange model （2CXM） in 28 consecutive HCC patients. A paired Student＇s t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and pearson correlation analysis was applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by pearson correlation analy- sis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by spearman correlation analysis. Results： The Fp value was greater than the PS value （Fp=1.07 mL/（mLomin）, PS= 0.19 mL/（mL·min） in the dual-input 2CXM. HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dualinput 2CXM, respectively. There were no significant differences in the Kcp, Vp, and HPI between the dual-input extended Torts model and the dual-input 2CXM （P=0.524, P=-0.569, P=0.622, respectively）. Except for Vo, other equivalent pharmacokinetic parameters were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dual-input 2CXM were correlated with Ktrans derived from the dual-input extended Tofts model （r=0.566, P=0.002; r=0.570, ,P=0.002）; Kep, Vp, and HPI between the two kinetic models were positive correlated （r=0.594, P=0.001; r=0.686, P=0.0001; r=0.391, P=0.004, respectively）. In the dual input extended Torts model, Vo was significantly less than in the dual input 2CXM （P=0.004）, and no significant correlation was seen between the two tracer kinetic models （r=0.276, P=0.156）. Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models （P〉0.05）. Conclusion： A dual-input two-compartment pharmacokinetic model can be used in assessing the microvascular physiopathological properties in the pretreatment of advanced HCC. The dual-input extended Torts model may be more stable in measuring the V,. However, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.