Quantitative Analysis Of Liver Fibrosis And Liver Function Using Specific Contrast Enhanced MRI In Rat Model

Objective:To investigate the potential of Gd-EOB-DTPA enhanced MR in diagnosing different stages of liver fibrosis, and to evaluate its value in quantitation of the hepatic function. To discover specific imaging biomarkers for liver fibrosis and hepatic function.Material and methods:Forty male Sprague-Dawley rats were used in the present study. Carbon tetrachloride (CCI4) was injected intraperitoneally in Sprague-Dawley rats for 4 (n=14)、8 (n=8) and 12 (n=8) weeks respectively to induce different stages of liver fibrosis (total number=30), while the control group(n=10) received normal saline (NS). At 4、8 and 12 weeks, rats from control group and experiment group were randomly selected to underwent magnetic resonance (MR) exams. MR exams were performed using Siemens MAGNETOM Skyra 3.0T with a wrist coil, obtaining unenhanced images、fast dynamic contrast-enhanced images、multi-hepatocyte-phase images and T1 mapping. For fast dynamic contrast-enhanced images, TWIST-VIBE sequence was used. Sixty images, including 3 pre-contrast measurements, were taken at intervals of 3s up to 3min after injection of the contrast agent, which was injected immediately after acquisition of the third measurement. For multi-hepatocyte-phase images, single phase TWIST-VIBE sequence was used. Twelve MR images were acquired at 5,10,15,20,25,30,35,45,50,55 and 60min after injection. For T1 mapping, double Flip Angel T13D VIBE sequence was used. Seven imagesets were acquired before and at 10,20,30,40,50 and 60min after injection. Data were analyzed using Siemens post-processing workstation. The following parameters were obtained:1) liver perfusion parameters such as ktrans、AUC、maximum relative enhancement (RE) and the time of maximum RE (Tmax); 2) hepatocyte-phase parameters such as relative enhancement (RE) at 3min (RE3min) 20min (RE20min)、 60min (RE60min) and elimination half-life of RE (T1/2); 3) T1 mapping parameters such as Tl reduction rate at different time point (AT1%) and elimination half-life of AT1%. Serum tests (ALT, AST, HA) were performed before MR exams and plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15) was measured after MR exams. Rats were then euthanized and their livers were removed for pathological examination. SPSS 21.0 was used for statistical analysis. The parameters in each groups was compared with one-way analysis of variance (one way ANOVA) and LSD test. The Pearson product-moment correlation coefficient was used to evaluate the relationship between the ICG R15 and the parameters. Values of P<0.05 were considered significant.Results:Eleven rats died during the study. In the end there were 19 rats in the hepatic fibrosis group [13 in S1-2 stage (early stage),6 in S3-4 stage (advanced stage)] and 10 rats in the control group [SO stage (normal stage)]. Ktrans, AUC and Ve decreased as the liver fibrosis progressed. Both AUC and Ve had statistical significant difference s between normal stage and early stage. Compared to normal and early stage groups, groups of advanced stage had significantly higher REmax, longer Tmax, TRE1/2, higher RE60min, as well as lower REchange, all these indicated a less amount of contrast agent intake and a slower contrast excretion in advance fibrosis. Similar to TRE1/2, T△T%1/2 was significantly longer in advance fibrosis compared to the other two groups. In the prediction of advanced liver fibrosis, REmax showd the best performance, with an area under the receiver operating characteristic curve of 0.958, a sensitivity of 100% and a specificity of 91.7% (cut off point=81.35%). In the prediction of early liver fibrosis, AUC has an area under the receiver operating characteristic curve of 0.796, a sensitivity of 61% and a specificity of 100%(cut off point=9.27). There was a correlation between TRE1/2 and ICG R15 (correlation coefficient= 0.754, P=0.002), but further study is still needed to confirm this result. ALT, AST, and HA increased as the fibrosis grade progresing, and LA was statistically significant between normal stage and early stage.Conclusion:Gd-EOB-DTPA enhanced MR could be helpful for the diagnosis of liver fibrosis. Among the above parameters, REmax had the best performance for diagnosing advanced liver fibrosis, while AUC may be helpful for detecting early fibrosis. There is a correlation between TRE1/2 and ICG R15, while further study is still needed.