基于X线相衬成像的CCl_4诱导肝纤维化微观结构成像研究
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摘要
目的探讨分析X线相衬成像(phase contrast imaging, PCI)技术在观察CCl_4肝纤维化模型病理学改变及微血管变化的应用价值。方法样本包括18只SD大鼠肝脏,按纤维化等级分为正常组、中度肝纤维化组和重度肝纤维化组,每组各6只;利用PCI技术对样品进行成像,同时对成像后的样品进行病理学检查。结果病理切片显示随着纤维化程度加重,胶原纤维面积比逐渐增大,3组间比较差异有统计学意义(P<0.01);PCI图像清晰地显示了肝脏微血管分布,微血管密度变化与病理切片结果一致,3组间微血管密度差异有统计学意义(P<0.01);随着纤维化程度的加重,血管分支增多,血管直径减小,同级血管直径3组间比较差异有统计学意义(P<0.01);肝脏表面纹理随纤维化的加重,逐渐变得凹凸不平或呈波浪状,纹理分析差异有统计学意义(P<0.05)。结论 PCI技术可清晰地显示大鼠纤维化肝脏微血管、表面纹理等微观结构变化,并进行相关指标的定量分析,为肝脏疾病的临床辅助诊断提供参考。
Objective To investigate the value of X-ray phase contrast imaging(PCI) in observing pathological and microvascular changes of liver fibrosis model induced by carbon tetrachloride(CCl4) in rats. Methods Eighteen Sprague-Dawley(SD) rats were divided into the normal group, moderate group and severe group based on different fibrosis grades. The livers of rats were imaged via X-ray PCI technology and examined for pathological changes after imaging.Results The pathological examination showed that the proportion of fibrosis area was gradually increased with the development of liver fibrosis, and there were significant differences among the three groups(P<0.01). Moreover, the projection images clearly showed the microvascular distribution in livers. The changes of microvessel density were consistent with pathological results, and significant differences were detected among the three groups(P<0.01). The vascular branches were increased with fibrosis progression. Conversely, vascular diameters decreased, and there was significant difference among the three groups(P<0.01). Additionally, surface texture of livers gradually became jagged or wavy, and texture analysis has significant difference(P<0.05). Conclusion X-ray PCI can clearly reveal the microstructural changes of the microvessel and surface texture of livers. Quantitative analysis of relevant indicators can also be performed, which provides some reference value for the clinical diagnosis and treatment of liver diseases.
Objective To investigate the value of X-ray phase contrast imaging(PCI) in observing pathological and microvascular changes of liver fibrosis model induced by carbon tetrachloride(CCl4) in rats. Methods Eighteen Sprague-Dawley(SD) rats were divided into the normal group, moderate group and severe group based on different fibrosis grades. The livers of rats were imaged via X-ray PCI technology and examined for pathological changes after imaging.Results The pathological examination showed that the proportion of fibrosis area was gradually increased with the development of liver fibrosis, and there were significant differences among the three groups(P<0.01). Moreover, the projection images clearly showed the microvascular distribution in livers. The changes of microvessel density were consistent with pathological results, and significant differences were detected among the three groups(P<0.01). The vascular branches were increased with fibrosis progression. Conversely, vascular diameters decreased, and there was significant difference among the three groups(P<0.01). Additionally, surface texture of livers gradually became jagged or wavy, and texture analysis has significant difference(P<0.05). Conclusion X-ray PCI can clearly reveal the microstructural changes of the microvessel and surface texture of livers. Quantitative analysis of relevant indicators can also be performed, which provides some reference value for the clinical diagnosis and treatment of liver diseases.
引文
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[22] Bech M,Tapfer A,Velroyen A,et al.In-vivo dark-field and phase-contrast x-ray imaging[J].Sci Rep,2013,3(11):17161-17175.
[2] Sun M,Kisseleva T.Reversibility of liver fibrosis[J].Clin Res Hepatol Gastroenterol,2015,39(1):S60-S63.
[3] Bataller R,Brenner DA.Liver fibrosis[J].Journal of clinical investigation.2005,111(2):209-218.
[4] Schuppan D,Afdhal NH.Liver cirrhosis[J].Lancet,2008,371(9615):838-851.
[5] 王一娇,唐少珊,赵国家.超声实时组织弹性成像评价大鼠肝纤维化分期[J].中国医学影像学杂志,2013,21(4):245-248.
[6] 王向阳,杨正汉,周诚.MR弹性成像及其临床应用[J].中国医学影像学杂志,2013,21(5):392-394.
[7] 胡春红,段敬豪,罗述谦.衍射增强成像的生物医学应用研究进展[J].国际生物医学工程杂志,2012,35(5):288-292.
[8] Xuan RJ,Zhao XY,Hu DD,et al.Three dimensional visualization of the microvasculature of bile duct ligation induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography[J].Sci Rep,2015,5(5):11500.
[9] Bedossa P,Carrat F.Liver biopsy:the best,not the gold standrad[J].J Hepatol,2009,50(1):1-3.
[10] 简建波,杨浩,秦莉莉,等.肝细胞癌微观结构的X线相衬CT成像研究[J].中国医学影像学杂志,2016,24(11):869-872.
[11] Winklhofer S,Peter S,Tischler V,et al.Diagnostic accuracy of quantitative and qualitative phase-contrast imaging for the ex vivo characterization of human coronary atherosclerotic plaques[J].Radiology,2015,277(1):64.
[12] Hu J,Cao Y,Wu T,et al.3D angioarchitecture changes after spinal cord injury in rats using synchrotron radiation phase-contrast tomography[J].Invest Radiol,2014,49(9):627-634.
[13] Cao Y,Zhang Y,Yin X,et al.3D visualization of the lumbar facet joint after ddegeneration using propagation phase contrast miro-tomography[J].Sci Rep,2016,6(6):21838.
[14] Fingerle AA,Willner M,Herzen J,et al.Simulated systic renal lesions:quantitative x-ray phase-contrast CT-an invitro phantom study[J].Radiology,2014,272(3):739-748.
[15] Fu Y,Peng HJ,Zhang X,et al.Assessment of fibrotic tissue and microvascular architecture by in-line phase-contrast imaging in a mouse model of liver fibrosis[J].Eur Radiol,2016,26(9):1-9.
[16] Zhang X,Yang XR,Chen Y,et al.Visualising liver fibrosis by phase-contrast X-ray imaging in common bile duct ligated mice[J].Eur Radiol,2013,23(2):417-423.
[17] Hu D,Chen,Y,Zhao X,et al.Anew conversation between radiology and pathology identifying microvascular architecture in stages of cirrhosis via diffraction enhanced imaging in vitro[J].PLoS One,2014,9(2):e87957.
[18] 刘骏桢,林江,严福华,等.同步辐射类同轴成像技术在大鼠肝脏小叶结构微血管显微成像中的应用[J].复旦学报:医学版,2015,42(1):112-118.
[19] 王明,李辉,王静,等,利用X射线衍射增强成像技术诊断肝纤维化[J],北京大学学报:医学版,2018,50(5):899-904.
[20] Holger H,Marian W,Sandra F,et al.Phase-contrast CT:qualitative and quantitative evaluation of atherosclerotic carotid artery plaque[J].Radiology,2014,271(3):870-878.
[21] Zhao Y,Brun E,Coan P,et al.High-resolution,low-dose phase contrast X-ray tomography for 3D diagnosis of human breast cancers[J].Proc Natl Acad Sci U S A,2012,109(45):18290-18294.
[22] Bech M,Tapfer A,Velroyen A,et al.In-vivo dark-field and phase-contrast x-ray imaging[J].Sci Rep,2013,3(11):17161-17175.