钆赛酸二钠增强磁共振灌注与多期肝胆期成像定量评价大鼠肝纤维化

Gadolinium Ethoxybenzyl Diethylene-triamine-pentaacetic-acid-enhanced Magnetic Resonance Imaging Perfusion and Multiple Hepatobiliary-phase Imaging for Quantitative Assessment of Liver Fibrosis in Rat Models

目的探讨钆塞酸二钠(Gd-EOB-DTPA)增强磁共振灌注参数与多期肝胆期参数对肝纤维化诊断的价值。方法 60只雄性SD大鼠,四氯化碳溶液腹腔注射构建不同分期的肝纤维化模型[实验组(n=45)、对照组(n=15)]。磁共振包括平扫、快速动态增强(3 min内连续扫描60期)与肝胆期多期成像(每5分钟1期,共60 min)。取病理进行肝纤维化分期。获得定量及半定量灌注参数[容量转运常量(K^(trans))、血管外细胞外间隙体积百分数(Ve)、初始曲线下面积(iAUC)、达峰时间(T_(max))等]、多期肝胆期参数[各时间点相对强化率(RE)、RE减半的时间(T_(RE1/2))、60 min RE下降程度(RE_(下降)=RE_(3 min)-RE_(60 min))]。采用单因素方差分析比较不同肝纤维化分级的上述参数,采用Spearman秩相关检验分析各参数与纤维化分期的相关性。结果随着肝纤维化加重,K^(trans)、iAUC、Ve减低(r=-0. 631,P=0. 002;r=-0. 503,P=0. 017; r=-0. 446,P=0. 037)。K^(trans)、Ve组间比较差异有统计学意义(F=7. 011,P=0. 005; F=4. 656,P=0. 023),重度肝纤维化组显著低于正常组(P=0. 001,P=0. 009)。T_(max)、T_(RE1/2)和RE下降组间比较差异有统计学意义(F=6. 633,P=0. 005; F=5. 493,P=0. 010; F=5. 343,P=0. 014),相较于正常组与轻度肝纤维化组,重度肝纤维化组的T_(max)、T_(RE1/2)显著延长(P=0. 005,P=0. 004; P=0. 008,P=0. 008),RE下降显著减低(P=0. 007,P=0. 012)。结论 Gd-EOB-DTPA增强磁共振灌注与多期肝胆期强化参数对于肝纤维化的诊断具有一定价值。

Objective To investigate the value of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid(Gd-EOB-DTPA)-enhanced magnetic resonance imaging(MRI)in detecting different stages of liver fibrosis in rats.Methods Rat models of liver fibrosis were induced by carbon tetrachloride intraperitoneal injection for 4-12 weeks(n=45).The control group was applied with 0.9%saline(n=15).The MRI protocol contained both dynamic contrast-enhanced sequence(60 continuous scans within 3 minutes,including three pre-contrast measurements)and multiple hepatobiliary-phase acquisitions(every 5 minutes after contrast injection,60 minutes in total).METAVIR score was used to grade liver fibrosis:normal(F0),mild fibrosis(F1-F2),and advanced fibrosis(F3-F4).Liver perfusion parameters[transfer constant(K trans),extravascular extracellular volume fraction(V e),initial area under curve(iAUC),maximum relative enhancement(RE max),and time of maximum RE(T max)]as well as hepatobiliary-phase parameters[RE at different time point,the decrease of RE(RE change=RE 3 min-RE 60 min),and elimination half-life of RE(T RE1/2)]were measured and compared with ANOVA analysis and Spearman rank correlation.Results Thirty-one rats completed MRI exams and were then divided into normal(n=10),mild fibrosis(n=10),and advanced fibrosis(n=11)groups.K trans,V e and iAUC decreased as liver fibrosis progressed(r=-0.631,P=0.002;r=-0.503,P=0.017;r=-0.446,P=0.037).K trans and V e showed significant differences among three groups(F=7.011,P=0.005;F=4.656,P=0.023).K trans and V e were significantly lower in advanced fibrosis group than in normal group(P=0.001,P=0.009).There were statistical significant differences of T max,T RE1/2 and RE change among groups(F=6.633,P=0.005;F=5.493,P=0.010;F=5.343,P=0.014).Compared to normal and mild fibrosis groups,advanced fibrosis group had significantly longer T max and T RE1/2(P=0.005,P=0.004;P=0.008,P=0.008)and significantly lower RE change(P=0.007,P=0.012).Conclusion Perfusion and multi-hepatobiliary-phase parameters such as K trans,V e,T max,T RE1/2 and RE change obtained from Gd-EOB-DTPA-enhanced MRI,may be valuable for detecting and staging liver fibrosis.