The Value Of MRI DWI And T1 Mapping In Evaluating Pirfenidone Against Hepatic Fibrosis In Mice

Objective:To evaluate antifibrotic effect of pirfenidone in a cholestatic liver fibrosis mice modle induced by partiacl bile duct ligation via 3.0T magnetic resonance imagine diffusion-weighted imaging,variable flip angle T1 mapping and histopathology.Materials and methods:63 healthy female Balb/C mice from the Experimental Animal Center of the Second Xiangya Hospital of Central South University were included in the experiment,27,21 mice were used as the experimental group A and group B separately,and the remaining 15 were used as the sham op group C（the abdominal wall was opened with the same incision and subsequently sutured）.Group A was injected with pirfenidone + PBS solution by ip（intraperitoneal injection）till 6w since PBDL operation,group B 、C was injected with the same dose of PBS solution at the same time period after operation.The operation group and sham op group were randomly divided into 3 subgroups at 2,4,and 6 weeks after the operation,and underwent 3.0T magnetic resonance scanning at specific time points,the sequences were T2-weighted single shot FSE 、T1-weighted FSE 、 diffusion-weighted imaging of two b values（b=0,800s/mm²）and variable flip angle T1 mapping,quantitative indicators apparent diffusion coefficient and T1 relaxation time were obtained from functional sequences,respectively.After MRI acquisition,the body weight was measured,blood was collected from the angular vein to analyze ALT and ALP level,and liver tissue was collected to measure the weight of the whole liver and ligated lobes.Then,the liver tissue was fixed,dehydrated,embedded,sliced and stained with H&E and Masson’s trichrome.All statistical analyses were performed using SPSS 22.0（SPSS Inc.,Chicago,IL,USA）and Origin Pro 2021（Origin Lab,Northampton,MA,USA）.P value of less than 0.05 was considered statistically significant.Results:1.Pathological changesAs the experiment proceed,the degree of liver fibrosis and the ratio of collagen area in the ligated lobe of the operation group showed an upward trend,and the collagen area ratio in group B > group A > group C（2w:11.23>7.07>1.13;4w:12.44>8.56>1.07;6w:13.26>10.44>1.07;unit:%）,with statistical significance（p < 0.05）.There was no difference in the Metavir and activity scoring systems and collagen area ratio between the non-ligated lobes and whole liver in experimental group and sham group,no liver fibrosis and inflammatory activities were observed.The grades of Metavir and activity scoring systems showed an upward trend with time.At the 6th week,the ligated lobes in the experimental group mostly reached the level of F3 and S2,and there was no statistical difference between the ligated lobes in experimental group.2.MRI parameter findingsThe ADC value decreased with the increase of collagen area ratio and the degree of liver fibrosis.ADC value : C > A（ligated lobe）>B（ligated lobe）(2w:1490.54>1302.71>1143.76;4w:1453.88>1178.49>1028.39;6w:1441.42>976.67>874.88;unit:10^-6um²/s)（p<0.05）.T1 relaxation time increased with the increase of collagen area ratio and the degree of liver fibrosis,T1 relaxation time: B（ligated lobe）>A（ligated lobe）>C（2w:1038.32>983.06>841.24;4w:1113.59>988.98>817.88;6w:1171.96>1113.53>852.38;unit:msec）（p < 0.05）.There was no significant difference in T1 relaxation time and ADC values between the non-ligated lobes of groups A,B and group C.ConclusionPirfenidone reduces collagen formation in cholestatic liver fibrosis,but has no inhibitory effect on inflammation.Multi-parameter magnetic resonance allows noninvasive evaluation of pirfenidone in the treatment of cholestatic liver fibrosis induced by PBDL in mice.Figures 10,Tables 3,References 62...