全肝CT灌注成像评估兔肝VX2瘤有效灌注及与免疫组织化学对比分析
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摘要
目的:分析兔VX2肝肿瘤模型的全肝CT灌注成像灌注参数与不成对动脉(unpaired arteries,UAs)、微血管面积(microvessel area,MVA)免疫组织化学指标的相关性,以进一步了解兔VX2肝肿瘤血管生成状况及与灌注成像表现的本质。方法:在术后2周对兔VX2肝肿瘤模型及假手术对照组兔行全肝CT灌注成像,获得兔VX2肝肿瘤组织、瘤周肝组织及假手术组的肝灌注血流量(blood fl ow,BF)、肝灌注血容量(blood volume,BV)、肝动脉灌注量(arterial liver perfusion,ALP)、门静脉灌注量(portal liver perfusion,PVP)、肝动脉灌注指数(hepatic perfusion index,HPI)等参数,并于检查完后通过免疫组织化学染色,获得肿瘤标本的UAs及MVA值。分析统计在有活力肿瘤边缘区(肝肿瘤组织)与瘤周肝组织的各CT灌注参数值之间的差异,各参数值与兔VX2肝肿瘤内的代表肿瘤新生细动脉的病理免疫组织化学指标UAs及代表血窦毛细血管化程度的MVA之间的关系。结果:实验组瘤组织与实验组瘤周肝组织和假手术组比较,全肝CT灌注参数BF,BV,ALP,PVP,HPI差异均有统计学意义(P<0.05)。但实验组瘤周肝组织与假手术组比较,全肝CT灌注参数BF,BV,ALP,PVP,HPI差异均无统计学意义(P>0.05)。免疫组织化学指标UAs与MVA呈正相关;肿瘤组织的BF,ALP,BV与UAs及MVA呈正相关,而PVP与UAs及MVA呈负相关,HPI与UAs呈正相关,HPI与MVA无显著相关。结论:全肝CT灌注可定量评估兔VX2肝肿瘤的肝动脉和门静脉灌注信息,并可在一定程度上反映肿瘤血管的生成状况。
Objective:To investigate the correlations among total liver CT perfusion parameters,unpaired arteries(UAs) and microvessel area(MVA) in a rabbit liver VX2 tumor model,and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.Methods:Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation.Perfusion parameters included blood flow(BF),blood volume(BV),arterial liver perfusion(ALP),portal liver perfusion(PVP),hepatic perfusion index(HPI) for the tumor rim and the surrounding liver tissue.After the examination,the UAs and MVA of tumor tissues were obtained by immunohistochemical staining.The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared.The correlations among perfusion parameters,UAs and MVA were analyzed.Results:There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group(P<0.05),but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control(P>0.05).There was positive correlation between UAs and MVA.UAs and MVA were positively correlated with BF,ALP and BV at the tumor rim.UAs and MVA were negatively correlated with PVP.HPI positively correlated with UAs,but it was not correlated with MVA.Conclusion:Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor,and to assess the degree of tumor angiogenesis.
Objective:To investigate the correlations among total liver CT perfusion parameters,unpaired arteries(UAs) and microvessel area(MVA) in a rabbit liver VX2 tumor model,and to learn the tumoral angiogenesis condition and the mechanisms for perfusion imaging.Methods:Rabbits with or without the inoculated VX2 tumor in the liver underwent total liver CT perfusion imaging 2 weeks after the operation.Perfusion parameters included blood flow(BF),blood volume(BV),arterial liver perfusion(ALP),portal liver perfusion(PVP),hepatic perfusion index(HPI) for the tumor rim and the surrounding liver tissue.After the examination,the UAs and MVA of tumor tissues were obtained by immunohistochemical staining.The differences of perfusion parameters between the vital tumor rim and the surrounding liver tissue were compared.The correlations among perfusion parameters,UAs and MVA were analyzed.Results:There was significant difference between the CT perfusion parameters at the tumor rim and the surrounding liver tissue or liver tissue of the control group(P<0.05),but there was no significant difference between the perfusion parameters at the surrounding liver tissues of the experimental group and the control(P>0.05).There was positive correlation between UAs and MVA.UAs and MVA were positively correlated with BF,ALP and BV at the tumor rim.UAs and MVA were negatively correlated with PVP.HPI positively correlated with UAs,but it was not correlated with MVA.Conclusion:Total liver CT perfusion can provide quantitative information to evaluate the artery and portal vein perfusion of liver VX2 tumor,and to assess the degree of tumor angiogenesis.
引文
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[2]Ippolito D,Capraro C,Casiraghi A,et al.Quantitative assessment of tumour associated neovascularisation in patients with liver cirrhosis and hepatocellular carcinoma:role of dynamic-CT perfusion imaging[J].Eur Radiol,2012,22(4):803-811.
[3]李辉,姜春霞,武明辉,等.兔VX2肝癌模型的建立及MRI表现[J].医药论坛杂志,2014,11:15-17.LI Hui,JIANG Chunxia,WU Minghui,et al.Establishment of rabbit VX2 hepatic carcinoma model and MRI manifestations[J].Journal of Medical Forum,2014,11:15-17.
[4]Choi SH,Chung JW,Kim HC,et al.The role of perfusion CT as a follow-up modality after transcatheter arterial chemoembolization:an experimental study in a rabbit model[J].Invest Radiol,2010,45(7):427-436.
[5]Jiang H J,Lu H B,Z hang ZR,et al.E x per imental study on angiogenesis in a rabbit VX2 early liver tumour by perfusion computed tomography[J].J Int Med Res,2010,38(3):929-939.
[6]Fink C,Bri x G,Hallibur ton SS,et al.Functional computed tomography imaging[J].Invest Radiol,2012,47(1):1.
[7]Kim CK,Lim JH,Park CK,et al.Neoangiogenesis and sinusoidal capillarization in hepatocellular carcinoma:correlation between dynamic CT and density of tumor microvessels[J].Radiology,2005,237(2):529-534.
[8]裴小青,刘隆忠,左菲菲,等.肝细胞癌的超声造影定量参数与肿瘤内新生动脉的相关性研究[J].中华超声影像学杂志,2011,20(3):222-225.PEI Xiaoqing,LIU Longzhong,ZUO Feifei,et al.Contrast-enhanced ultrasonography of hepatocellular carcinoma:correlation between quantitative parameters and arteries in neoangiogenesis[J].Chinese Journal of Ultrasonography,2011,20(3):222-225.
[9]Sabo E,Boltenko A,Sova Y,et al.Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma[J].Clin Cancer Res,2001,7(3):533-537.
[10]赵志华,廖锦堂,唐宏伟.超声造影在肝脏局灶性病变定性诊断中的价值[J].临床超声医学杂志,2014,9:637-640.ZHAO Zhihua,LIAO Jintang,TANG Hongwei.Value of contrsastenhanced ultrasonography in qualitative diagnosis of focal liver lesions[J].Clin Ultrasound in Med,2014,9:637-640.
[11]Pei XQ,Liu LZ,Zheng W,et al.Contrast-enhanced ultrasonography of hepatocellular carcinoma:correlation between quantitative parameters andarteries in neoangiogenesis or sinusoidal capillarization[J].Eur J Radiol,2012,81(3):e182-e188.
[12]Sato M,Nakai Y,Nakata W,et al.Microvessel area of immature vessels is a prognostic factor in renal cell carcinoma[J].Int J Urol,2014,21(2):130-134.
[13]Yang F H.Perfusion computed tomography evaluation of angiogenesis in liver cancer[J].Eur Radiol,2010,20(6):1424-1430.
[14]Guan L.Angiogenesis dependent characteristics of tumor observed on rabbit VX2 hepatic carcinoma[J].Int J Clin Exp Pathol.2015,8(10):12014-12027.
[15]Zhang LJ,Wu S,Wang M,et al.Quantitative dual energy CT measurements in rabbit VX2 liver tumors:Comparison to perfusion CT measurements and histopathological findings[J].Eur J Radiol,2012,81(8):1766-1775.
[16]Sun JH,Zhang YL,Nie CH,et al.Considerations for two inoculation methods of rabbit hepatic tumors:Pathology and image features[J].Exp Ther Med,2012,3(3):386-390.
[17]Zhou P,Zhou P,He W,et al.The influence of blood supply on high intensity focused ultrasound a preliminary study on rabbit hepatic VX2 tumors of different ages[J].Acad Radiol,2012,19(1):40-47.
[18]Cazejust J,Bessoud B,Colignon N,et al.Hepatocellular carcinoma vascularization:from the most common to the lesser known arteries[J].Diagn Interv Imaging,2014,95(1):27-36.
[19]Jia HS,Quan XY,Zeng S,et al.Dynamic evaluation of rabbit VX2hepatic carcinoma with CT and MRI[J].Journal of First Military Medical University,2002,22(2):141-144.
[20]Dav id G,Ciurea AV,Iencean SM,et al.Angiogenesis in the degeneration of the lumbar intervertebral disc[J].J Med Life,2010,3(2):154-161.
[21]Tsushima Y.Development of perfusion CT software for personal computers[J].Acad Radiol,2002,9(8):922-926.
[22]Miles KA.Functional computed tomography in oncology[J].Eur J Cancer,2002,38(16):2079-2084.
[23]Folberg R,Hendrix MJC,Maniotis AJ.Vasculogenic mimicry and tumor angiogenesis[J].Am J Path,2000,156(2):361-381.
[24]Aziz SA,Sznol JA,Albiges L,et al.Microvessel area as a predictor of sorafenib response in metastatic renal cell carcinoma[J].Cancer Cell Int,2014,14(1):4.
[25]Kudo M.Imaging diagnosis of hepatocellular carcinoma and premalignant/borderline lesions[J].Semin Liver Dis,1999,19(3):297-309.