High-resolution 3D visualization of ductular proliferation of bile duct ligation-induced liver fibrosis in rats using x-ray phase contrast computed tomography

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.

Fine-scale visualizing the hierarchical structure of mouse biliary tree with fluorescence microscopy method

“…Our approach has numerous advantages, which is better than previous reported methods of visualization, including X-ray micro-CT scanning, resin casting and ink retrograde injection [10,12,23]. First of all, our method has a high resolution and we can see the outline of each hepatocyte.…”

High‐resolution 3D imaging of microvascular architecture in human glioma tissues using X‐ray phase‐contrast computed tomography as a potential adjunct to histopathology

“…Except the 3D visualization, a virtual micro‐endoscopy (VME) technique was also applied in this study. VME provided a novel method for visualization of the inner vascular architecture on basis of the 3D reconstruction; details about of this technique had been available elsewhere . With the help of PCCT, thrombi inside the vessels can also be clearly found.…”

“…VME provided a novel method for visualization of the inner vascular architecture on basis of the 3D reconstruction; details about of this technique had been available elsewhere. 21,26 With the help of PCCT, thrombi inside the vessels can also be clearly found. Stenosis rate was used to evaluate stenosis severity of the vessel, which is defined as follow:…”

3D analysis of microvasculature in murine liver fibrosis models using synchrotron radiation-based microtomography

“…However, the spatial resolution of in vivo μCT scans is limited to 35 μm voxel edge length [6]. With the use of synchrotron radiation-based microtomography (SRμCT), by providing a high photon flux and phase-sensitive imaging protocols, spatial resolutions of 10.9 to 3.5 μm isometric voxel sizes were reached in the assessment of liver fibrosis [12][13][14][15][16][17]. While a detailed depiction and characterization of macrovessels and smaller intrahepatic arterioles and venules was achieved, the sinusoidal vascular bed remained beyond the spatial resolution capacities in previous studies.…”