Hu Dou-dou, Chen Yu, Bihi Ali, Li Xin-min, Wang Tai-ling, Wang Bao-en, Zhao Xin-yan
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
PLoS One. 2014 Feb 4;9(2):e87957. doi: 10.1371/journal.pone.0087957. eCollection 2014.
BACKGROUND/AIM: Diffraction enhanced imaging (DEI) is a synchrotron radiation X-ray phase-contrast imaging technique that can better reveal the microstructure of biological soft tissues than conventional X-rays. The aim of this study is to investigate the angio-architectural changes of the liver during fibrosis, cirrhosis and its subsequent regression by applying synchrotron radiation based DEI.
DEI experiments were performed at the 4W1A station of Beijing Synchrotron Radiation Facility. Twenty-four Sprague-Dawley rats were induced with liver fibrosis by carbon tetrachloride (CCl4) for up to 10 weeks, after which spontaneous regression started and continued until week 30. Quantitative analysis of the DEI images yielded the mean vascular density and intercapillary distance, which was then re-confirmed by immunohistochemical analysis of CD34.
Based on the DEI results, the mean vascular density was 1.4-fold higher in fibrotic rats (at week 6) and 2-fold higher in cirrhotic rats (at week 10) compared with the control (p<0.05). Accordingly, the intercapillary distance decreased to 563.89 ± 243.35 µm in fibrotic rats and 392.90 ± 92.68 µm in cirrhotic rats compared with 673.85 ± 214.16 µm in the control (p<0.05). During fibrosis regression at week 30, vascular density was 0.7-fold lower and intercapillary distance increased to 548.60 ± 210.94 µm as compared with cirrhotic rats (p<0.05).In parallel to the DEI results, immunohistochemical analysis of CD34 showed similar changes.
Synchrotron-based DEI can conduct radiological as well as pathological analysis. Our results are consistent with previous reports indicating that angiogenesis is directly proportional to fibrosis progression. Furthermore, by clarifying the vascular characteristics of liver diseases, DEI reveals that cirrhosis cannot fully reverse during fibrosis regression.
背景/目的:衍射增强成像(DEI)是一种同步辐射X射线相衬成像技术,与传统X射线相比,它能更好地揭示生物软组织的微观结构。本研究旨在通过应用基于同步辐射的DEI技术,研究肝纤维化、肝硬化及其后续消退过程中肝脏血管结构的变化。
在北京同步辐射装置的4W1A实验站进行DEI实验。24只Sprague-Dawley大鼠用四氯化碳(CCl4)诱导肝纤维化长达10周,之后开始自发消退并持续至第30周。对DEI图像进行定量分析得出平均血管密度和毛细血管间距,然后通过CD34免疫组化分析进行再次确认。
基于DEI结果,纤维化大鼠(第6周)的平均血管密度比对照组高1.4倍,肝硬化大鼠(第10周)比对照组高2倍(p<0.05)。相应地,纤维化大鼠的毛细血管间距降至563.89±243.35µm,肝硬化大鼠降至392.90±92.68µm,而对照组为673.85±214.16µm(p<0.05)。在第30周纤维化消退过程中,与肝硬化大鼠相比,血管密度降低0.7倍,毛细血管间距增加至548.60±210.94µm(p<0.05)。与DEI结果平行,CD34免疫组化分析显示出相似变化。
基于同步辐射的DEI可进行放射学及病理学分析。我们的结果与先前报道一致,表明血管生成与纤维化进展成正比。此外,通过阐明肝脏疾病的血管特征,DEI显示肝硬化在纤维化消退过程中不能完全逆转。