The value of MR T1rho for assessing the evolution and severity of liver fibrosis in carbon tetrachloride model rats

Objective To investigate the changes of liver spin-lattice relaxation time (T1rho) values in the rotating frame in the progression and regression of carbon tetrachloride (CCl4)-induced model rats with liver fibrosis and the diagnostic values for staging liver fibrosis. Methods Eighty rats were prospectively enrolled and randomly divided into the CCl4 group (n=49), the regression group (n=20) and the control group (n=11). All rats were labeled and then examined using MRI at baseline. The liver fibrosis model was established by subcutaneous injection of 40% CCl4 in hackles. The CCl4 group underwent black-blood T1rho imaging at the end of the 4th, 6th, 8th, 10th, 12th week post CCl4 injection. The regression group underwent black-blood T1rho imaging at the end of the 4th, 6th week post CCl4 injection and the end of 1st, 2nd, 4th, 6th week post CCl4 withdrawal (the injection was stopped at the end of the 6th week). The control group was injected with the same amount of corn oil at the same time point and underwent black-blood T1rho imaging at the end of 4th, 6th, 8th, 10th, 12th week. The liver T1rho values were measured in each group over time. Independent-samples t test was used to analyze the differences of liver T1rho values in adjacent time points. The experimental mice were divided into no liver fibrosis group (S0), mild liver fibrosis group (S1, 2) and moderate or severe liver fibrosis group (S3, 4). The differences of liver T1rho values were analyzed in different fibrosis stages by Kruskal-Wallis H test. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of T1rho values in staging liver fibrosis. The correlation between liver T1rho values and fibrosis stages was analyzed using Spearman correlation coefficient. Results Fifty-nine rats completed the whole experiment, including 28 rats in the CCl4 group, 20 rats in the recovery group and 11 rats in the control group. In the CCl4 group, the liver T1rho values gradually increased, reached the maximum at the end of week 8, and then gradually decreased. There was statistically significance in liver T1rho values at the adjacent time points (P 0.05) in control group. The T1rho values in the no liver fibrosis group (S0, n=15), the mild liver fibrosis group (S1, 2, n=23) and the moderate or severe liver fibrosis group (S3, 4, n=21) were [36.3(34.4,41.4)], (47.2±8.4), (48.8±9.0) ms, respectively. The liver T1rho values increased with the aggravation of the liver fibrosis, and there was a low positive correlation between them (r=0.402, P=0.001). There were statistically significant differences in T1rho values among the three groups (P<0.01).The area under the curve values to distinguish no liver fibrosis (S0) from liver fibrosis (S1 to 4) and no or mild liver fibrosis (S0 to 2) from moderately or severe liver fibrosis (S3,4) were 0.825 (95% confidence intervals is 0.720 to 0.931) and 0.668 (95% confidence intervals is 0.540 to 0.796), separately. Conclusion The liver T1rho values are useful for evaluating the progression and regression of liver fibrosis. It has a moderate diagnostic value to assess the presence of liver fibrosis, but a low diagnostic value to differentiate no or mild liver fibrosis from moderately to severe liver fibrosis. Key words: Liver fibrosis; Rat; Carbon tetrachloride; Magnetic resonance imaging