基于实时剪切波弹性成像和影像纹理分析的儿童肝移植术后肝纤维化早期诊断研究

Compared with adult liver transplantation, graft fibrosis after pediatric liver transplantation had a high incidence and rapid progression which increase the risk of retransplantation. Traditional liver biopsy is an invasive examination, which causes great damage to children. Conventional liver function examination including ALT and AST can’t reflect the progression of liver fibrosis. Hence, there is a lack of non-invasive and specificity method for the early diagnosis of graft fibrosis in pediatric recipients. Real time shear wave elastography can quantitatively detect liver stiffness through an elastography image while ultrasonic imaging texture analysis can further extract and quantify the ultrasonic texture feature of the liver tissue, the combination of which may be helpful in early diagnosis of hepatic fibrosis. In our previous study, we combined real-time shear wave elastography and ultrasound texture analysis in rat liver fibrosis model, the pilot result showed that the elasticity value and texture feature were consistent with pathological results. Therefore, we propose to use real time shear wave elastography and ultrasonic imaging texture analysis to detect mild-term graft fibrosis in pediatric liver transplant recipients. Firstly, we will perform real time shear wave elastography and ultrasonic imaging texture analysis to observe the progressive of hepatic fibrosis through rat model. And then we will obtain the optimal threshold for the diagnosis of liver fibrosis in pediatric recipients after liver transplantation and further to conduct a prospective study. The results of this study will provide a noninvasive and dynamic quantitative assessment method for early diagnosis of liver fibrosis.

相较于成人肝纤维化，儿童肝移植术后肝纤维化具有发生率高，进展快，二次移植风险高的特点。传统肝穿活检是有创检查，儿童穿刺的风险较成人更大，而常规ALT、AST肝功能指标无法反映肝纤维化进程，因而目前儿童肝纤维化缺乏无创特异的早期诊断手段。实时剪切波弹性成像可测量和评估组织的硬度变化，纹理分析可提取和量化图像的纹理特征，两者结合可获取组织的“触觉”弹性信息和“视觉”纹理信息。我们前期在大鼠肝纤维化模型中结合实时剪切波弹性成像和超声影像纹理分析，并与组织病理对照，发现与病理结果相符。因此，我们提出应用实时剪切波弹性成像和超声纹理分析能早期诊断儿童肝移植术后肝纤维化。本研究拟首先观察实时剪切波弹性成像和超声纹理分析对大鼠早期肝纤维化的诊断效能；结合已收集的儿童肝移植术后肝穿病理，获取两者对儿童肝移植术后肝纤维化诊断的最佳阈值，并进一步行前瞻性研究。为儿童肝移植术后肝纤维化的早期无创诊断提供新方法。

相较于成人肝纤维化，儿童肝移植术后肝纤维化具有发生率高，进展快，二次移植风险高的特点。传统肝穿活检是有创检查，儿童穿刺的风险较成人更大，而常规ALT、AST肝功能指标无法反映肝纤维化进程，因而目前儿童肝纤维化缺乏无创特异的早期诊断手段。实时剪切波弹性成像可测量和评估组织的硬度变化，纹理分析可提取和量化图像的纹理特征，两者结合可获取组织的“触觉”弹性信息和“视觉”纹理信。.本研究首先基于大鼠肝纤维化模型，应用实时剪切波弹性成像和超声影像纹理分析，并与组织病理对照，分析实时剪切波弹性成像与超声影像纹理分析对大鼠肝纤维化的诊断效能。大鼠肝纤维化F0-F1vsF2-F3(≧F2)和F0-F2vsF3,实时剪切波弹性成像的阈值取7.35kPa和9.25kPa时,ROC曲线下的面积是0.98(95%CI,0.96～1.00)和0.99(95%CI,0.98～1.00)，敏感性和特异性分别为93.3%和92.7%，97.3%和92.0%。通过Fisher、POE+ACC和MI特征约简，选择了30个纹理特征子集。鉴别大鼠肝纤维化F0-F1vsF2-F3(≧F2)时，5个最优纹理参数分别为平均值、百分位数90%、百分位数99%、方差和SumVarnc，其灵敏度和特异度分别为72.7%～90.9%和62.7%。鉴别F0-F2vsF3，5个最优纹理参数分别为Mean，百分位数10%，百分位50%，AngScMom和InvDfMom，其敏感度和特异度分别为80.00%～100.0%和73.3%～93.7%。.收集儿童肝移植术后肝穿病理，获取实时剪切波弹性成像和超声纹理分析对儿童肝移植术后肝纤维化诊断的最佳阈值。二维剪切波弹性成像诊断移植肝纤维化在S1期、S2期、S3期、S4期的敏感性和特异性分别为73.3%，81.8%，100%，100%和87.5%，91.7%，100%和100%，诊断阈值分别为7.85，8.20，12.75和16.20kPa。二维剪切波弹性成像可用于儿童肝移植术后移植肝纤维化的无创评估，减少肝穿刺活检的次数。儿童肝移植术后肝功能稳定的患儿，正常移植肝弹性值为7.5kPa，二维剪切波弹性成像评估移植肝纤维化的弹性阈值为8.2kPa。 .本研究的开展将为儿童肝移植术后肝纤维化的早期无创诊断提供新方法。