Song Xiao-Jing, Wang Shu-You, Jia Shu-Yong, Wang Guang-Jun, Zhang Wei-Bo
Department of Biomedical Engineering, Institute of Acupuncture & Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
Quant Imaging Med Surg. 2023 Oct 1;13(10):6434-6445. doi: 10.21037/qims-23-122. Epub 2023 Aug 10.
Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in experimental studies. In this study, we established a multimodal imaging approach for liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research.
In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured.
multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice.
Utilizing multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.
肝功能的可视化评估是肝病学研究中的一个热点话题。在实验研究中，用于评估肝功能的可靠且实用的可视化方法较少。在本研究中，我们建立了一种用于肝功能评估的多模态成像方法，并将健康小鼠与慢性酒精性肝损伤（cALI）模型小鼠进行比较，以探索其在实验研究中的潜在适用性。
利用体内荧光成像（IVFI）技术直观呈现吲哚菁绿在健康小鼠和cALI模型小鼠肝脏中的清除情况。通过使用靶向肝细胞去唾液酸糖蛋白受体的Cy5.5-半乳糖基化聚赖氨酸探针，经IVFI评估肝脏储备功能。通过肝脏血流灌注的激光散斑灌注成像评估肝脏微循环。然后通过共聚焦激光内镜显微镜成像研究肝脏微观结构。最后，测量肝脏去唾液酸糖蛋白受体表达、组织学以及血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。
多模态成像结果直观且动态地显示，模型小鼠中吲哚菁绿清除率[平均值±标准差（SD）：30.83±14.71，95%置信区间（CI）：20.3至41.35]、靶向去唾液酸糖蛋白受体的Cy5.5-半乳糖基化聚赖氨酸的荧光信号强度（平均值±SD：1217.92±117.63；95%CI：1148.38至1290.84）和荧光聚集面积（平均值±SD：5855.80±1271.81；95%CI：5051.57至6653.88）以及肝脏血流灌注（平均值±SD：1494.86±299.33；95%CI：1316.98至1690.16）均显著低于健康小鼠（所有P<0.001）。与健康小鼠相比，模型小鼠肝脏去唾液酸糖蛋白受体表达显著下降（平均值±SD：219.03±16.34；95%CI：208.97至230.69；P<0.001），血清丙氨酸氨基转移酶（平均值±SD：149.70±47.89 U/L；95%CI：81.75至128.89；P=0.01）和天冬氨酸氨基转移酶水平升高（平均值±SD：106.30±36.13 U/L；95%CI：122.01至180.17；P=0.021），肝细胞肿胀变形，肝索结构消失，部分坏死，肝细胞解体。肝脏区域荧光信号、肝脏血流灌注和微观结构的成像特征与模型小鼠肝脏去唾液酸糖蛋白受体表达、肝功能血清指标及组织病理学具有生物学相关性。
利用多模态成像技术评估肝功能是一种可行的实验研究方法，能够快速提供动态且直观的可视化评估。
