Abstract
X-ray phase-contrast computed tomography (PCCT) can provide excellent image contrast for soft tissues with small density differences, and it is particularly appropriate for three-dimensional (3D) visualization of accurate microstructures inside biological samples. In this study, the morphological structures of proliferative bile ductules (BDs) were visualized without contrast agents via PCCT with liver fibrosis samples induced by bile duct ligation (BDL) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group, 2-week and 6-week post-BDL groups. All livers were removed after euthanasia for a subsequent imaging. The verification of the ductular structures captured by PCCT was achieved by a careful head-to-head comparison with their corresponding histological images. Our experimental results demonstrated that PCCT images corresponded very well to the proliferative BDs shown by histological staining using cytokeratin 19 (CK19). Furthermore, the 3D density of proliferative BDs increased with the progression of liver fibrosis. In addition, PCCT accurately revealed the architecture of proliferative BDs in a 3D fashion, including the ductular ramification, the elongation and tortuosity of the branches, and the corrugations of the luminal duct surface. Thus, the high-resolution PCCT technique can improve our understanding of the characteristics of ductular proliferation from a new 3D perspective.
Highlights
Corresponding to the different types of liver injury, the dynamic and diverse reconstruction of the biliary architecture may represent an adaptive response of the tissue, and should have several physiological advantages[1]
Our previous study confirmed that phase contrast computed tomography (CT) (PCCT) can clearly depict the microvascular structures from different stages of liver fibrosis induced by bile duct ligation (BDL) without contrast agents, but accurate visualizations of proliferative bile ductules (BDs) cannot be presented on account of the restriction of the charge coupled device (CCD) spatial resolution[15]
Liver fibrosis induced by BDL in rats was used to perform the experiment without contrast agents, and the proliferative BDs were visualized using PCCT
Summary
Corresponding to the different types of liver injury, the dynamic and diverse reconstruction of the biliary architecture may represent an adaptive response of the tissue, and should have several physiological advantages[1]. PCCT has been widely used in biological tissue imaging, including that of the kidney, hepatocellular carcinoma, hepatic alveolar echinococcosis, spinal cord, breast cancer and coronary atherosclerotic plaques[6,7,8,9,10,11] This technique presents new possibilities for analysing and characterizing the anatomical and pathological features of diseased microvasculature in liver fibrosis. Our previous study confirmed that PCCT can clearly depict the microvascular structures from different stages of liver fibrosis induced by BDL without contrast agents, but accurate visualizations of proliferative BDs cannot be presented on account of the restriction of the charge coupled device (CCD) spatial resolution[15]. The structural visualization of ductular proliferation may facilitate the study of pathological changes associated with cholestatic liver fibrosis induced by BDL. The purpose of this study was to observe 3D structures of proliferative BDs and explore the corresponding ductular reaction mechanisms and the development changes of proliferative BDs during the course of liver fibrosis induced by BDL using PCCT
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