基于X射线相衬CT研究肝纤维化微血管动态变化及其对门脉高压形成的作用机制

Dynamic changes of the microvasculature, involving the formation of new vessels (angiogenesis) and the establishment of abnormal angio-architecture of the liver, are regarded as one of the most important and newly discovered pathophysiological features of fibrosis, and contribute to developing and maintaining portal hypertension. In this study, X-ray phase-contrast computed tomography (PCCT) is used to explore the regulating role of the microvascular changes in portal hypertension. This study mainly includes: 1). A PCCT reconstruction algorithm is proposed from few-view projection data, and its application in the microvasculature imaging of hepatic fibrosis is investigated. 2) The microstructure of collagen fibrils in liver is reconstructed using PCCT, and the analysis of fibrotic bands, regenerative nodules and other pathological characteristics of fibrosis is performed to evaluate the degree of fibrosis. 3) There-dimensional (3D) structure of the microvasculature in hepatic fibrosis is reconstructed, and microvascular features, including morphological and quantitative changes in the microvasculature, are utilized to assess the changes of the microvasculature. 4) Based on 3D visualization technology, the effect of collagen accumulation on the dynamic changes of the microvasculature is explored. This study still investigates the mechanism of microvascular changes and the regulating role of microvascular changes in portal hypertension during the development of fibrosis. Additionally, the correlation and regression analyses are applied to examine the relationship between microvascular change and portal pressure, and the significant microvascular features are screened to evaluate or prognose the portal hypertension. The study aims to offer a reliable, objective and noninvasive tool for the stage and evaluation of hepatic fibrosis, and provide a new sight to investigate the formation mechanisms of portal hypertension.

肝脏微血管动态变化是近来发现的最重要的肝纤维化病理生理特征之一，微血管形态异常改变和血管新生是门脉高压形成的重要原因。本项目拟应用相衬CT技术，研究肝纤维化微血管动态变化及其对门脉高压形成的作用机制。研究内容：1) 研究基于稀疏角度的相衬CT重建算法及其在肝纤维化微血管成像的应用。2) 应用相衬CT重建肝脏胶原纤维微观结构，通过对纤维隔和纤维结节等的分析，辅助肝纤维化程度的评估。3) 应用相衬CT重建肝纤维化微血管三维结构，研究表征微血管形态和数量改变的影像学参数指标。4) 基于三维可视化技术，探索胶原纤维增生对微血管动态变化的影响，研究纤维化发展过程中微血管变化机理，以及微血管变化对门脉高压形成的机制。通过微血管动态变化与门脉压力的相关和回归分析，筛选表征门脉高压的特征影像学指标。期望本项目的研究为肝纤维化评估和分级提供新的无创检查技术和评估方法，为门脉高压形成机制的研究提供创新的思路。

肝内微血管变化被认为是肝纤维化发展中最重要的病理生理学特征之一，微血管形态异常改变和血管新生是门脉高压形成的重要原因。X射线相衬CT能够高分辨率地呈现生物软组织的三维（three-dimensional, 3D）微脉管结构。本项目利用相衬CT技术，研究肝纤维化发展中微血管变化及其对门脉高压形成的作用，主要研究内容和结果包括：(1) 结合生物软组织成像特点，发展了基于稀疏投影的低剂量相衬CT重建算法，研究了相衬CT在肝纤维化分析上的关键技术。同时对相衬CT重建中的投影旋转中心校正、伪影去除进行研究，提高了CT重建质量。(2) 利用相衬CT清楚地显示出血管、纤维隔和纤维结节等肝硬化特征结构，从3D角度初步研究了胶原纤维与血管结构的微观显示。(3) 选取CCl4诱导大鼠肝纤维化模型为研究对象，利用相衬CT重建出纤维化发展中3D精细微血管结构，研究表明利用3D微血管变化能够很好地评估肝纤维化进展。(4) 利用相衬CT重建了胆管结扎（BDL）诱导大鼠肝纤维化组织及人体胆汁性肝硬化组织中的3D脉管微观结构，定量分析了纤维化发展中脉管微观结构的改变，区分了不同类型的血管和胆管。(5) 构建了BDL诱导的大鼠胆道梗阻性肝硬化的3D动态模型，利用相衬CT结合组织病理学观察和量化了胆管系统及其伴随的血管系统整体和局部结构，探讨了由胆道压力增加引发的胆管树自适应性关键形态学变化。同时，这种3D虚拟病理学技术和胆道系统的适应模式在胆道闭锁患者的肝组织外植体中得到验证。(6) 研究证实了纤维化发展中肝内微血管变化与门脉压力具有显著相关性。综上，本研究表明相衬CT是一种准确评估肝纤维化或肝硬化微脉管病变的新技术，它从3D微脉管角度为门脉高压形成机制研究提供了创新的思路，同时为肝纤维化评估和分级提供了新的无创检查技术。

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