3.0T^1H-MRS在食蟹猴不同程度肝纤维化中的对比研究

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

目的探讨食蟹猴不同程度肝纤维化的氢质子磁共振波谱(1H-MRS)的变化规律,为研究人类不同程度肝纤维化的1H-MRS奠定理论依据。方法以四氯化碳(CCl4)成功建立22只食蟹猴的肝纤维化模型,其中发展至早期肝硬化(肝纤维化S4期)的有15只。对具有肝纤维化完整发展过程的15只食蟹猴的1H-MRS进行对比研究,分析食蟹猴不同程度肝纤维化的1H-MRS的变化规律。各研究指标的比较采用配伍组设计方差分析,组间两两比较用SNK q检验;1H-MRS研究指标与肝纤维化严重程度的相关性采用Spearman秩相关分析。结果食蟹猴1H-MRS的Cho随着肝纤维化严重程度的加重而增大,且肝纤维化各期(S1~S4)与正常肝组织(S0期)比较、重度肝纤维化S3、S4期与轻-中度肝纤维化S1、S2期比较,差异均有统计学意义(P<0.01)。与S0期比较,S1期的lipid峰值明显增高,S2期有所回落,S3、S4期的lipid峰值则明显低于S0期,且肝纤维化S1、S3、S4期与S0期比较,差异均有统计学意义(P<0.01)。随着肝纤维化严重程度的进展,Cho/lipid比值逐渐增大且组间差异均有统计学意义(P<0.01),Cho/lipid比值与肝纤维化病理学分期的秩相关系数达0.98(P<0.001)。ROC曲线分析显示,Cho/lipid比值为肝纤维化最具诊断意义的指标,Cho/lipid比值诊断肝纤维化和早期肝硬化的阈值分别为:肝纤维化≥0.028、早期肝硬化≥0.131(P<0.01)。结论食蟹猴肝纤维化模型的1H-MRS随着肝纤维化严重程度的加重而发生规律性变化,其中Cho/lipid比值是肝纤维化分期最有诊断价值的指标,该规律可为研究人的肝纤维化奠定理论基础。

Objective To investigate the changing rules with 1H magnetic resonance spectroscopy(1H-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(CCl4).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 1H-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 1H-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 1H-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.