| X-ray phase-contrast imaging(PCI) is an emerging technique that utilizes a new imaging mechanism to resolve the problems of biological soft tissues imaging. PCI has approximately 1000 times greater sensitivity than conventional radiography in imaging soft tissues and its spatial resolution can be on the order of microns or even sub-microns. Combined with computed tomography(CT), PCI has been successfully extended to CT mode recently, resulting in X-ray phase-contrast computed tomography(PCCT), which enables the visualization of the interior features within the samples non-invasively. Thus, PCCT has high research value and broad applications in the biomedical imaging.In this paper, liver fibrosis, cirrhosis and hepatocellular carcinoma(HCC) tissues were imaged using in-line PCCT. 3D microstructures in these diseases were reconstructed and computer-aided image analysis of these microstructures based on PCCT was also performed. The main research contents are as follows:1. Investigation of the dynamic changes of collagen and angio-architecture during fibrosis and its subsequent regression based on PCCT. Liver fibrosis was induced by carbon tetrachloride(CCl4) and the samples were divided into four groups: normal, moderate, severe liver fibrosis and reversion group. Three-dimensional(3D) visualization of the vessels in each group was performed via PCCT. In this study, fibrosis area rate was used to evaluate the collagen accumulation; texture analysis was utilized to distinguish the roughness of the hepatic surface in different groups; and 3D micro-vessel density(3D-MVD), tortuosity and vessel branch angles were applied to analyse the microvascular changes. The results showed that fibrosis area was gradually increased, and the surface of the liver became coarser, and meanwhile, the 3D-MVD, tortuosity and vessel branch angles kept increase during the fibrosis process. During its subsequent regression, all the parameters analysed above were declined but the fibrosis did not fully reverse during the fibrosis regression.2. To investigate the potential of PCCT with iodine contrast in imaging collagen structure in liver cirrhosis. In this study, CCl4-induced liver cirrhosis models in rats and viral or biliary cirrhosis in humans were imaged via PCCT. CT slices were reconstructed and then compared with the corresponding pathological sections to confirm the accuracy of the PCCT. Moreover, fibrosis area rate and width of fibrous septa were applied to assess the correlation between the CT slices and the pathological sections in imaging the collagen structure. In addition, fibrosis volume rate, expressed as a relative percentage between the volume of fibrosis and the total volume, was proposed to evaluate the collagen accumulation in 3D modality. In human cirrhosis tissues, 3D vasualization of the collagen was performed and the distribution characteristics of the collagen structure in viral and biliary cirrhosis was analysed, respectively. The results showed that PCCT with iodine contrast could clearly reveal the fibrous septa and pseudolobule, which were the feature structures of cirrhosis, and significant positive correlations for the fibrosis area rate and width of fibrous septa were observed between the CT slices and the pathological sections in imaging the collagen structure(R ≥ 0.856, P < 0.01). Meanwhile, the result of the fibrosis volume rate was very close to the fibrosis area rate measured via histopathologic findings. In human samples, PCCT with iodine staining was verified to be also appropriate in imaging collagen structure in cirrhosis. 3D structure of the collagen in human cirrhosis was clearly shown in this study, and the distribution of the collagen structure had close relation to the angiogenesis in the viral cirrhosis, while the collagen structure was distributed with the ductular proliferation in the biliary cirrhosis.3. Mircro-imaging of the microstructures such as microvasculature, capillarized sinusoids and trabecular structure in the development of the HCC. In this study, eight resected human HCC tissues, which were divided into two groups: low-grade(well/moderately-differentiated; four cases) and high-grade(poorly-differentiated; four cases) HCC, were imaged by PCCT. Fine structures in HCC tissues were revealed. Quantitative analyses of the capillarized sinusoids(i.e., percentage of sinusoidal area(PSA), sinusoidal volume) and trabecular structure(i.e., trabecular thickness, surface-area-to-volume ratio(SA/V)) in low-grade and high-grade HCC groups were performed. The results showed that the alterations of these microstructures were clearly observed in 3D geometry using PCCT, which was confirmed by the corresponding histological sections. Moreover, based on quantitative analysis results, the alterations of the capillarized sinusoids and trabecular structure could be expressed as follow: low-grade HCC showed many small capillarized sinusoids and thin trabecular structure with a high SA/V, while high-grade HCC demonstrated a few large capillarized sinusoids and thick trabecular structure with a low SA/V.This study presented the dynamic changes of the collagen and microvasculature during fibrosis and its subsequent regression based on PCCT; revealed the collagen structure of cirrhosis in rats and humans using PCCT with iodine contrast; and quantitatively evaluated the variation of the microstructures such as capillarized sinusoids and hepatic trabeculae in the development of HCC, which provided a new method to image the microstructures in liver disease. |
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