Department of Radiology, Seoul National University Hospital, Seoul, Korea.
Institute of Radiation Medicine, Seoul National University Hospital, Seoul, Korea.
Sci Rep. 2017 Oct 27;7(1):14203. doi: 10.1038/s41598-017-14218-x.
We investigated serial changes of the Kupffer cell (KC) function and hepatic oxygen saturation (sO) using contrast-enhanced ultrasound imaging (CEUS) and photoacoustic imaging (PAI) in preneoplastic changes during cholangiocarcinogenesis induced by obstructive cholangitis and N-nitrosodimethylamine in a mouse model. The CEUS and PAI were performed to assess Sonazoid contrast agent uptake by KC and changes in the sO of liver parenchyma. An extensive bile ductular reaction, cystic dilatation, and epithelial hyperplasia with dysplastic changes were noted in the experimental group. During the preneoplastic changes, the parenchymal echogenicity on the Kupffer-phase of CEUS was continuously decreased in the experimental group, and which means that the Sonazoid phagocytosis by KC was decreased. The number of KCs was increased in the CD68 analysis, indicating functionally impaired KCs. There was a simultaneous serial decrease in sO on PAI measurement of the experimental group during the preneoplastic changes. The experimental group also showed significantly higher expression of hypoxia-inducible factor-1α and vascular endothelial growth factor protein. Our study demonstrated that KC dysfunction and hypoxic environmental changes were the factors influencing preneoplastic change during cholangiocarcinogenesis, and we could non-invasively monitor these changes using CEUS and PAI.
我们使用对比增强超声成像（CEUS）和光声成像（PAI）在梗阻性胆管炎和 N-亚硝二甲胺诱导的胆管癌发生前变化期间研究了枯否细胞（KC）功能和肝氧饱和度（sO ）的连续变化在小鼠模型中。进行 CEUS 和 PAI 以评估 Sonazoid 造影剂被 KC 摄取以及肝实质 sO 的变化。实验组观察到广泛的胆管反应、囊性扩张和上皮增生伴发育不良改变。在癌前病变过程中，实验组的 CEUS 枯否细胞期实质回声强度持续降低，这意味着 KC 摄取 Sonazoid 减少。CD68 分析中 KC 的数量增加，表明功能受损的 KC。在癌前病变过程中，实验组的 PAI 测量 sO 也同时连续下降。实验组还显示缺氧诱导因子-1α 和血管内皮生长因子蛋白的表达显著升高。我们的研究表明，KC 功能障碍和缺氧环境变化是胆管癌发生过程中影响癌前病变的因素，我们可以使用 CEUS 和 PAI 进行非侵入性监测这些变化。
