A comparative study of 3.0T (1)H-MRS for varying degrees of liver fibrosis in cynomolgus monkeys

Abstract

Objective: To investigate the changing rules with (1)H magnetic resonance spectroscopy ((1)H-MRS) in order to provide human research theoretical basis with varying degrees of liver fibrosis in cynomolgus monkeys. Methods: Liver fibrosis model in twenty-two cynomolgus monkey was successfully established with carbon tetrachloride (CCl(4)). Among them, fifteen cynomolgus monkey developed to early-stage liver cirrhosis (S4 stage). A comparative study was conducted in 15 cynomolgus monkeys that had fully developed liver fibrosis. The changing rules for varying degrees of liver fibrosis in cynomolgus monkeys were analyzed with (1)H-MRS. Supplementary methods: statistical analysis was performed using compatibility group design and analysis of variance for each research indicators. SNK-q test was used for pairwise comparison between the groups. The correlation between the 1H-MRS research indicators and the severity of liver fibrosis was analyzed by Spearman's rank correlation. Results: The Cho of (1)H-MRS was increased with the severity of liver fibrosis in cynomolgus monkeys. Moreover, there were statistically significant (P < 0.01) differences between liver fibrosis staging (S1 ~ S4) and normal liver tissue (S0 stage), severe liver fibrosis staging (S3 and S4) and mild to moderate liver fibrosis staging (S1 and S2). Compared with S0 stage, the peak value of lipid in S1 stage was significantly higher than that of S2 stage, and the peak value of lipid in S3 and S4 stage was significantly lower than that of S0 stage, and the differences between S1, S3, S4 and S0 stages were statistically significant (P < 0.01). The Cho/lipid ratio had gradually increased with the severity of liver fibrosis progression and the differences between groups were statistical significant (P < 0.01). Spearman's rank correlation coefficient between Cho / lipid ratio and pathological stage of liver fibrosis was 0.98 (P = 0.000). ROC curve analysis showed that Cho / lipid ratio was the most significant diagnostic indicator for liver fibrosis. The threshold values of CHO/lipid ratio were≥ 0.028, and≥ 0.131 (P < 0.01) for the diagnosis of liver fibrosis and early-stage cirrhosis. Conclusion: (1)H-MRS of the cynomolgus monkey liver fibrosis model changes rules regularly with the aggravation of severity of liver fibrosis. Among them, the Cho/lipid ratio is the most valuable indicator for the diagnosis of liver fibrosis staging, which may provide a theoretical basis for the study of human liver fibrosis.