大鼠肝硬化肝癌SPIO增强MRI表现与Kupffer细胞的关系

SPIO-enhanced MR Imaging of the Rat with Cirrhosis and Hepatocellular Carcinoma:Relationship with Kupffer Cells of Liver

目的:建立二乙基亚硝胺(DENA)诱导的大鼠肝硬化肝细胞癌(HCC)模型,探讨超顺磁性氧化铁(SPIO)增强MRI上肝硬化肝癌信号改变与肝Kupffer细胞(KCs)之间的关系。方法:22只大鼠肝硬化肝癌模型,其中6只为单纯性肝硬化,16只为肝硬化肝癌,对照组为10只清洁级Wistar雄性大白鼠,均行SPIO增强前后T1WI和T2WI扫描,并行病理检查(HE染色及普鲁士蓝染色),分析肝脏Kupffer细胞数量与SPIO增强后信号之间的关系。结果:普鲁士兰染色切片上肝硬化组织内蓝染Kupffer细胞数量略减少,蓝色颗粒不均匀;高分化肝癌中Kupffer细胞减少,低分化肝癌Kupffer细胞显著减少甚至消失。肝癌与正常肝实质、硬化肝组织相比,Kupffer细胞数量减少,差异有显著性意义(P<0.001);正常肝实质与肝硬化组织内Kupffer细胞数量的差异无显著性意义(P=0.088)。SPIO增强T2WI上,正常肝实质、肝硬化组织信号强度(SI)较增强前明显下降,信号强度下降百分比(PSIL)分别为42%和38%,两组间差异无统计学意义(P=0.409);肝癌信号强度较增强前无明显下降,PSIL为12%,明显低于正常肝实质和肝硬化组织(P<0.001);SPIO增强后肝癌对比噪声比(CNR)较增强前显著提高(P=0.002)。SPIO增强T1WI上,正常肝实质及硬化肝组织PSIL分别为15%和6%,而肝癌的信号强度较增强前升高9%,部分小病灶呈不均匀轻度强化,肝癌CNR较增强前明显降低(P<0.001)。SPIO增强T2WI上,肝组织PSIL与Kupffer细胞数量呈曲线趋势,随着组织内Kupffer细胞数量的增多病灶信号强度下降程度越明显,曲线估计3次模型决定系数R2为0.920,有显著性意义(P<0.001)。结论:SPIO增强T2WI上肝脏信号强度改变与Kupffer细胞数量及其吞噬功能有相关性,随着Kupffer细胞增多PSIL呈升高趋势。SPIO增强MRI不仅能提高肝癌的对比,改善病变的检测和特征描述,且能间接反映组织内Kupffer细胞数量,可以预测肝癌的组织学分级。

Objective：To establish the, model of （DENA） induced hepatocellular carcinoma （HCC） and cirrhosis of rat and to study their signal intensity （SI） on superparamagnetic iron oxide （SPIO）-enhanced MR images and the relationship with the amount of Kupffer cells （KCs）. Methods：Twenty-two rats with DENA induced HCC and cirrhosis were studied, including simple cirrhosis （6 rats） and HCC associated with cirrhosis （16 rats）. Ten normal wistar male rats served as the control group. MRI （T1WI,T2WI） before and after SPIO enhancement were performed with a 1.5T whole body scanner. Pathology examination （HE and Prussian blue staining） were done and the relationship between the amount of KCs and the signal intensities （SI） on the images before and after SPIO-enhanced MRI were analyzed. Results： On the slices of cirrhosis with Prussian blue stain, the amount of KCs was slightly reduced,in which the blue particles were heterogeneously distribu- ted. The amount of KCs in well-differentiated HCC was moderately reduced,in poorly-differentiated HCC was obviously reduced and even disappeared. The amount of KCs in HCCs was significantly lesser than that of the normal liver parenchyma and cirrhosis （P（0. 001）, while there was no significant difference between the normal liver tissue and cirrhosis （P= 0. 088）. On SPIO enhanced T2 WI,SI of normal hepatic parenchyma and cirrhosis was obviously lower than that before SPIO enhancement, and the percentage of SI lessening （PSIL） was 42% and 38 % respectively, with no statistical difference, （P = 0. 409）. The signal intensity of HCC on SPIO-enhanced T2WI was similar to those images before enhancement, PSIL was 12% ,which was obviously lower than the normal liver parenchyma and cirrhosis （P〈0. 001）. CNR of HCC on SPIO-enhaneed T2 WI was significantly higher than that before enhancement （P= 0. 002）. On SPIO-enhanced T1 WI, PSIL of normal liver and cirrhosis was 15% and 6% respectively,whereas the SI of HCC increased by 9% compared with that before enhancement,some of the small HCCs showed slightly inhomogeneous enhancement. CNR of HCC was obviously lower than that before enhancement （P〈0. 001）. On SPIO enhanced T1WI,the PSIL of liver parenchyma and amount of KCs showed a curvilinear tendency, the SI descended obviously along with the increase of the amount of KCs. R2 （Rsq） of Cubic models of curve estimation was 0. 920 and marked statistical significance was existed （P〈0. 001 ）. Conclusion： Changes of signal intensities of liver on SPIO enhanced T2 WI were correlated with the amount and phagocytic function of KCs, PSIL increased along with the increase of the amount of KCs. SPIO-enhanced MRI not only could improve the contrast of HCC,the detection ability of focal hepatic lesions as well as their morphology characteristics, but also could indirectly reflect the amount of KCs in liver tissues and was helpful in predicting the histology grade of HCC.