磁共振灌注加权成像对食蟹猴肝纤维化的诊断价值

目的分析食蟹猴不同程度肝纤维化的磁共振灌注加权成像(MR-PWI)定量参数值的变化规律,探讨评价肝纤维化严重程度的MR-PWI最佳检测指标。方法以皮下注射四氯化碳溶液辅以饲喂高脂饲料的方法成功建立22只食蟹猴的肝纤维化模型,其中15只发展至早期肝硬化(即肝纤维化S4期)。采用配伍组设计对具有肝纤维化完整发展过程的15只食蟹猴进行Exchange肝脏双血供模型的MR-PWI对比研究,MR-PWI定量参数包括对比剂容积转运常数(k^trans)、反流速率常数(k_ep)、血管外细胞外间隙容积分数(v_e)、对比剂血浆容积分数(v_p)、肝动脉灌注指数(HPI)。分析不同程度肝纤维化上述参数的变化规律及其与肝纤维化严重程度的相关性,并探讨最佳的MR-PWI检测指标。统计学方法采用配伍组设计(随机区组设计)方差分析、SNK-q检验、Spearman秩相关分析和ROC曲线分析。结果食蟹猴MR-PWI的k^trans、k_ep随着肝纤维化进展而下降,差异均有统计学意义(F=685.228、99.718,P均<0.01),肝纤维化各期(S1~S4)与正常肝组织(S0期)比较,差异均有统计学意义[(0.527±0.038)、(0.479±0.035)、(0.432±0.032)、(0.387±0.031)mL/min比(0.584±0.044)mL/min,P均<0.01;(2.193±0.307)、(1.997±0.301)、(1.624±0.174)、(1.532±0.130)mL/min比(2.565±0.482)mL/min,P均<0.01];重度肝纤维化S3、S4期与轻度肝纤维化S1期和中度肝纤维化S2期比较,k^trans、k_ep差异均有统计学意义(P均<0.01);但S3与S4期、S1与S2期的k^trans、k_ep比较差异均无统计学意义(P均>0.05)。随着肝纤维化严重程度的进展,HPI逐渐增大,差异有统计学意义(F=839.883,P<0.01),S0~S4期HPI分别为0.244±0.022、0.317±0.035、0.421±0.046、0.546±0.043、0.651±0.058,各组间两两比较差异均有统计学意义(P均<0.01)。随着肝纤维化严重程度的进展,v_p逐渐降低,v_e逐渐增大,但S0~S4期组间比较差异均无统计学意义(P均>0.05)。Spearman秩相关分析显示,k^trans、k_ep与肝纤维化严重程度呈负相关(r_s=-0.875、-0.797,P均<0.01),HPI与肝纤维化程度呈正相关(rs=0.959,P<0.01)。ROC曲线分析结果显示,k^trans、k_ep和HPI诊断早期肝硬化的AUC分别为0.852(95%CI 0.767~0.937)、0.799(95%CI 0.700~0.897)和0.967(95%CI 0.932~1.002),最佳截断值分别为0.395 mL/min、1.561 mL/min和0.590,灵敏度分别为86.7%、79.6%和97.4%,特异度分别为77.4%、71.9%和93.1%。其中HPI诊断S1、S2、S3和S4期肝纤维化的最佳截断值分别为0.291、0.376、0.503和0.590,灵敏度分别为95.7%、93.8%、94.4%和97.4%,特异度分别为89.5%、84.7%、91.3%和92.7%。结论食蟹猴肝纤维化模型的MR-PWI参数值随肝纤维化发展而发生规律性变化,其中HPI是定量评价肝纤维化严重程度的最佳检测指标。

Diagnostic value of magnetic resonance-perfusion weighted imaging in liver fibrosis of cynomolgus monkeys

Objective To analyze the change rules of quantitative parameters of magnetic resonance-perfusion weighted imaging(MR-PWI)in cynomolgus monkeys with different degrees of liver fibrosis,and to explore the best parameter of MR-PWI in evaluating the severity of liver fibrosis.Methods Liver fibrosis models of twenty-two cynomolgus monkeys were successfully established by subcutaneous injection of carbon tetrachloride and feeding with high-fat food.Among them,15 cynomolgus monkeys developed into early liver cirrhosis(stage S4 of liver fibrosis).Compatibility group design was adopted,the comparative study on MR-PWI of exchange double blood supply model of liver was carried out in these 15 cynomolgus monkeys with a complete development process of liver fibrosis.The quantitative parameters of MR-PWI included endothelial transfer constant(k^trans),reflux rate constant(k_ep),extravascular extracellular space fractional volume(v_e),fractional plasma volume(vp)and hepatic artery perfusion index(HPI).The change rules of the above parameters and their correlation with the severity of hepatic fibrosis were analyzed.The best parameter of MR-PWI was explored.Compatibility group design(randomized block design),analysis of variance,SNK-q test,Spearman rank correlation analysis and receiver operating characteristic(ROC)curve analysis were used for statistical analysis.Results k^trans and kep of MR-PWI of cynomolgus monkeys decreased along with the progress of hepatic fibrosis,and the differences were statistically significant(F=685.228,99.718,both P<0.01).There were statistically significant differences between each stage of hepatic fibrosis(S1 to S4)and normal liver tissue(S0)((0.527±0.038),(0.479±0.035),(0.432±0.032)and(0.387±0.031)mL/min vs.(0.584±0.044)mL/min,all P<0.01;(2.193±0.307),(1.997±0.301),(1.624±0.174)and(1.532±0.130)mL/min vs.(2.565±0.482)mL/min,all P<0.01).There were statistically significant in k^trans and k_ep between stage S3,S4 severe liver fibrosis and stage S1 mild liver fibrosis,stage S2 moderate liver fibrosis(all P<0.01),however there were no statistically significant differences between stage S3 and stage S4 liver fibrosis,between stage S1 and stage S2 liver fibrosis(all P>0.05).Along with the development of the severity of liver fibrosis,HPIs increased gradually,and the differences were statistically significant(F=839.883,P<0.01).The HPIs of stage S0 to S4 were 0.244±0.022,0.317±0.035,0.421±0.046,0.546±0.043 and 0.651±0.058,respectively,and there were statistically significant differences between groups(all P<0.01).Along with the progression of the severity of liver fibrosis,v_p decreased while v_e increased gradually,but there were no statistically significant differences among groups(all P>0.05).The results of Spearman rank correlation analysis indicated that k^trans and k_ep were negatively correlated with the severity of liver fibrosis(r_s=-0.875 and-0.797,both P<0.01),however HPI was positively correlated with the severity of liver fibrosis(rs=0.959,P<0.01).The results of ROC curve analysis showed that area under curves(AUCs)of k^trans,k_ep and HPI in the diagnosis of early cirrhosis were 0.852(95%CI 0.767 to 0.937),0.799(95%CI 0.700 to 0.897)and 0.967(95%CI 0.932 to 1.002),respectively.The best cut-off values were 0.395 mL/min,1.561 mL/min and 0.590,respectively.The sensitivity was 86.7%,79.6%and 97.4%,respectively and the specificity was 77.4%,71.9%and 93.1%,respectively.The thresholds of HPI in the diagnosis of liver fibrosis at stage S1,stage S2,stage S3 and stage S4 were 0.291,0.376,0.503 and 0.590,respectively;the sensitivity was 95.7%,93.8%and 94.4%and 97.4%,respectively and the specificity was 89.5%,84.7%,91.3%and 92.7%,respectively.Conclusions The parameters of MR-PWI change regularly with the development of liver fibrosis in the cynomolgus monkey model,among which HPI is the best parameter for quantitative evaluation of the severity of liver fibrosis.