超声造影改良双输入模型定量检测犬肝硬化肝血流及其对肝储备功能的影响

Pre-operative assessment of liver reserve function byindocyanine green (ICG)clearance testis an important procedure to determine the amount of liver resection and to reduce the risk of post-operative liver failure. Hepatic blood flow has a large impact on ICG, however, the impact comes from hepatic artery blood flow, portal vein blood flow or total hepatic blood flow is not clear. ICG variation is caused by the change of hepatic blood flow or the variation of hepatic blood flow is caused by ICG change is also not fully understood. The main reason is the lack of accurate, non-invasive and quantitative method for assessing hepatic blood flow. Electromagnetic flow meter is golden standard but invasive, Doppler ultrasound is non-invasive but its accuracy is not convinced. CT has radiation and its temporal resolution is low.In this study, firstly, CC14 fibrosis/cirrhosis models of dog at various stages are established. Dual-input one-compartment model that has mature application on CT liver perfusion technique is introduced into quantitative measurement of hepatic blood flow of dog with contrast-enhanced ultrasound (CEUS). Meanwhile, CEUS-based destruction replenishment method is applied to assess hepatic flow rate constant and flow parameter. Then,electromagnetic flow meter is used as golden standard for measuring the blood flow of hepatic artery and portal vein. The accuracy of flow quantification of hepatic artery, portal vein and liver parenchyma of dog is analyzed.Key technique of CEUS quantification and comprehnsive parameters are screened and determined.Finally, analyze the impact of hepatic blood flow on liver reserve function, and then provide newi deas and technologies for quantifying liver blood flow and evaluating liver reserve function clinically.

术前检测肝脏储备功能（基于吲哚菁绿ICG清除试验）是决定肝切除量及降低术后肝衰的重要举措。然而ICG受肝血流量影响大，但受肝动脉或门静脉还是整体血流影响及血流和ICG改变孰先孰后的研究不多，主要原因是缺乏准确、无创的肝血流定量检测方法。电磁血流计是金标准但有创，超声多普勒检测无创但准确性不高，CT可测定肝灌注但有射线且时间分辨力较低。本研究拟首先建立犬CCl4不同程度肝纤维化/硬化模型，将肝脏CT灌注技术中已成熟应用的双输入单室模型（DIOCM）引入超声造影（CEUS）的犬肝血流定量分析中，并同时应用CEUS击破再灌注法测定肝血流速率常数及流量参数；然后以电磁血流计为金标准，分析CEUS检测犬纤维化/硬化肝肝动脉、门静脉及肝实质血流量的准确性并筛选及确定CEUS定量检测的关键技术及综合参数；最后分析犬肝血流量对肝储备功能的影响。进而为临床定量检测肝血流及评估肝脏储备功能提供新的思路及技术。

术前检测肝脏储备功能（基于吲哚菁绿ICG清除试验）是决定肝切除量及降低术后肝衰的重要举措。然而ICG受肝血流量影响大，但受肝动脉或门静脉还是整体血流影响及血流和ICG改变孰先孰后的研究不多，主要原因是缺乏准确、无创的肝血流定量检测方法。电磁血流计是金标准但有创，超声多普勒检测无创但准确性不高，CT可测定肝灌注但有射线且时间分辨力较低。本研究通过建立新西兰兔CCl4不同程度肝纤维化模型，运用超声造影（CEUS）定量评估了肝动脉，门静脉及肝实质在肝纤维化过程中的血流动力学变化，以流量计为金标准，分析了CEUS检测兔纤维化/硬化肝肝动脉、门静脉及肝实质血流量的准确性并筛选了CEUS定量检测的主要参数；使用弹性超声测量了不同程度肝纤维化肝硬度；最后讨论了肝血流量及肝脏硬度与肝储备功能的关系。实验结果显示随着肝纤维化的进展，超声造影相关系数：门静脉峰值强度（PV-Imax）逐渐降低，肝动脉峰值强度（HA-Imax）逐渐升高。PV-Imax与流量计所测出的门静脉血流量（PV-BV）之间的相关系数较高，Spearman r为0.553（p＜0.0001）。随着肝纤维化的进展，肝脏储备功能降低，ICGR15（吲哚菁绿15分钟滞留率）逐渐增高，在肝纤维化分期（F0-F4）F2期时的ICGR15就显著高于F0期（p＜0.01）。PV-Imax在F2时较F0期也表现出了显著差异（p＜0.0001）；LP-MTT 在F2期时显著短于F0期（p＜0.01）。HA-Imax，LP-Imax在F4期时才较F0期的相应参数出现显著改变（p＜0.001），HA-MTT在F3期时显著高于F0期HA-MTT（p＜0.0001）。PV-Imax与PV-BV一致性较好，PV-Imax、LP-MTT能较早地反映肝纤维化过程中肝脏血流动力学的改变，与肝脏储备功能（ICGR15）的显著改变时期一致；肝纤维化过程中肝脏硬度与肝脏储备功能的改变密切相关(Spearman r=0.7497, p<0.0001)。