| X-ray phase contrast imaging(PCI)has been demonstrated to be advantageous in revealing detailed structures inside biological specimens.Unlike conventional absorption-based x-ray imaging,the contrast in PCI arises from the phase shift that xrays suffer when they travel through a sample.Generally,PCI has 1000-fold greater sensitivity than conventional absorption-based x-ray imaging.Combined with the advantages of PCI and computed tomography(CT),x-ray phase contrast CT(PCCT)has been developed.There are many advantages in PCCT compared with absorptionbased CT,where biological samples show very weak absorption contrast.Thus,PCCT is very suitable for soft tissue evaluation with small density variations.In this study,liver fibrosis induced by common bile duct ligation(BDL)and human biliary liver cirrhosis tissues were imaged using PCCT.Three-dimensional(3D)microvascular microstructures of these samples were reconstructed and quantitative analysis of the microstructures based on PCCT was also performed to evaluate the liver fibrosis development.The research contents mainly include the following two parts:(1).This paper first explored the possibility on 3D visualization of the ductular proliferation of liver fibrosis induced by bile duct ligation in rats using x-ray PPCT.Ten Sprague-Dawley(SD)rats were used in the study.All animals were divided into the following two groups: the sham operation group and BDL group.Each group contained 5 rats.To further explore the feasibilities in clinical application of PCCT,the sample of human biliary liver cirrhosis from the patient was used to be as experimental validation.The results showed that high-resolution 3D imaging by PCCT can accurately detect the microstructures of the bile ductular lumen and inner walls in BDL rats.The clear visualization of the proliferative bile ductules(BDs)without injecting contrast allowed us to confirm that ductular proliferation could cause ductular ramification,the elongation and tortuosity of the branches,and the orrugation of the luminal duct surface.A comparison of the CT images with the histological sections of the samples highlighted the high degree of sensitivity of the PCCT technique as a noninvasive imaging modality.In addition,the evagination could also be observed in the two-dimensional(2D)CT images and histological sections obtained from the liver samples of the human biliary liver cirrhosis.In the wake of developments in PCCT,this technique may play an auxiliary role in monitoring the ductular proliferation of chronic liver diseases.(2).To further understand and observe the adaptive remodelling changes of BDs in liver fibrosis.We used a higher number of specimens and groups based on different time points in the subsequent studies.Liver samples were respectively harvested at 0,2,4,6 and 8 weeks post-BDL and Each group contained 8 rats.The 3D microvasculature was reconstructed and the 3D microvascular density was obtained.Combined with the PCCT and 3D visualization,the microstructure of proliferative BDs was reconstructed in different stages of liver fibrosis,and the 3D density of proliferative BDs and fractal dimension(FD)were quantitatively analyzed.Moreover,the experimental study explored the the change of portal pressures in a rat model of liver fibrosis.The results showed that quantitative changes in the microvasculature,which were characterized by 3D microvascular density,showed obvious changes during the progression of liver fibrosis.Furthermore,the fibrosis areas,the density of proliferative BDs and the number of arteries increased with development of liver fibrosis.The absence of vessels at the end of the portal vein,ductular proliferation and collagen fibers could result in portal hypertension within.Interestingly,portal pressures did not show a change in value under the influence of the adhesions to the arteries,vein anastomoses and lymphatic hyperplasia.The study demonstrated that PCCT could provide a novel means and a new direction to assess the severity of liver fibrosis based on microvascular change. |
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