钆塞酸二钠增强MRI对急性肝衰竭犬模型肝功能的评估价值
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摘要
目的探讨钆塞酸二钠(Gd-EOB-DTPA)行MRI增强扫描对急性肝衰竭(ALF)犬模型肝功能评估的意义。方法选取健康成年雄性Beagle犬16只,随机分为ALF组(n=8)和空白对照组(n=8),ALF组以0. 5 ml/kg剂量分别于前肢隐静脉注射30%乙酰氨基酚,腹部皮下注射40%四氯化碳,12 h后同样的途径半数剂量注射30%乙酰氨基酚和40%四氯化碳进行造模。24 h后进行Gd-EOB-DTPA增强MRI扫描,注射对比剂Gd-EOB-DTPA(0. 15 ml/kg体质量)后分别测定平扫期及肝细胞期20 min、26 min不同时间段高、中、低不同信号区的信号值,并于不同信号区选定一区域行肝穿刺。对照组直接采用Gd-EOB-DTPA增强MRI扫描,在相应区域进行肝穿刺,穿刺取得的组织分别进行HE染色及电镜检查,对比组间、组内不同信号值的差异性及HE染色、电镜结果。计量资料同一时间点2组间比较采用独立样本t检验,组内不同时间点的比较采用重复测量方差分析,组内同一时间不同信号值比较采用单因素方差分析。结果 ALF组行Gd-EOB-DTPA增强MRI扫描后不同时期内呈现高、中、低不同信号强度,高、中、低信号区域HE染色及电镜下显示肝细胞呈不同程度的破坏。ALF组给药前,给药6 h、12 h、24 h不同时间点ALT、AST、TBil水平比较差异均有统计学意义(F值分别为54. 909、148. 238、11. 778,P值均<0. 01); ALF组和对照组在平扫期、MRI增强扫描20 min、MRI增强扫描26 min时同一信号值(高、中、低)间比较差异均有统计学意义(ALF组:F值分别为232. 69、65. 39、24. 91,P值均<0. 01;对照组:F值分别为800. 43、817. 35、795. 71,P值均<0. 01); ALF组平扫期、MRI增强扫描20 min、MRI增强扫描26 min时高、中、低信号值间比较差异均有统计学意义(F值分别为3. 914、24. 343、22. 424,P值均<0. 05)。2组间MRI增强20 min时中信号、低信号值比较差异均有统计学意义(t值分别为-7. 813、-7. 492,P值均<0. 001),MRI增强扫描26 min时高、中、低信号值比较差异均有统计学意义(t值分别为-3. 075、-4. 785、-6. 326,P值分别为0. 008、<0. 001、<0. 001)。对应的信号降低与HE病理及电镜观察肝细胞破坏程度相关。结论 Gd-EOB-DTPA行MRI增强扫描对ALF犬类肝功能的评价具有可行性,同时可以推测肝组织病理损害程度。
Objective To investigate the value of Gd-EOB-DTPA-enhanced MRI in the assessment of liver function in dogs with acute liver failure( ALF). Methods A total of 16 healthy adult male Beagle dogs were randomly divided into ALF group and blank control group,with 8 dogs in each group. The dogs in the ALF group were given injection of 30% acetaminophen via the saphenous vein of the forelimb and abdominal subcutaneous injection of 40% carbon tetrachloride at a dose of 0. 5 ml/kg,and 12 hours later,30% acetaminophen and 40% carbon tetrachloride were injected at half of the first dose. Gd-EOB-DTPA-enhanced MRI scan was performed after 24 hours,and after injection of the contrast agent Gd-EOB-DTPA( 0. 15 ml/kg body weight),the signal values of high-,medium-,and low-signal regions were measured during plain scan and at 20 and 26 minutes of MRI scan. Liver puncture was performed in different signal regions. Gd-EOB-DTPA-enhanced MRI was performed for the control group,and liver puncture was performed in the corresponding regions. HE staining and electron microscopy were used for tissue examination,and the two groups were compared in terms of signal values and the results of HE staining and electron microscopy. The independent samples t-test was used for comparison of continuous data at each time point between the two groups,and an analysis of variance with repeated measures was used for comparison at different time points within groups; a one-way analysis of variance was used for comparison of signal values at each time point within groups. Results The ALF group had high,medium,and low signals in different time periods after Gd-EOB-DTPA-enhanced MRI scan,and HE staining and electron microscopy showed varying degrees of hepatocyte injury in the high-,medium-,and low-signal regions. The ALF group had significant differences in the levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin at 0,6,12,and 24 hours( F = 54. 909,148. 238,and 11. 778,all P < 0. 01). In the ALF group and the control group,the high-,medium-,and low-signal values showed significant changes during plain scan and at 20 and 26 minutes of MRI scan( ALF group: F = 232. 69,65. 39,and 24. 91,all P < 0. 01; control group: F = 800. 43,817. 35,and 795. 71,all P < 0. 01). In the ALF group,there were significant differences in the high-,medium-,and low-signal values during plain scan and at 20 and 26 minutes of MRI scan( F = 3. 914,24. 343,and 22. 424,all P < 0. 05). There were significant differences between the two groups in the medium-and low-signal values at 20 minutes of MRI scan( t =-7. 813 and-7. 492,both P < 0. 001) and the high-,medium-,and low-signal values at 26 minutes of MRI scan( t =-3. 075,-4. 785,and-6. 326,P =0. 008,P < 0. 001,and P < 0. 001). The reduction in corresponding signals was associated with the degree of hepatocyte injury. Conclusion Gd-EOB-DTPA-enhanced MRI scan is feasible for the assessment of liver function in ALF dogs,and it can also predict the degree of liver pathological damage.
Objective To investigate the value of Gd-EOB-DTPA-enhanced MRI in the assessment of liver function in dogs with acute liver failure( ALF). Methods A total of 16 healthy adult male Beagle dogs were randomly divided into ALF group and blank control group,with 8 dogs in each group. The dogs in the ALF group were given injection of 30% acetaminophen via the saphenous vein of the forelimb and abdominal subcutaneous injection of 40% carbon tetrachloride at a dose of 0. 5 ml/kg,and 12 hours later,30% acetaminophen and 40% carbon tetrachloride were injected at half of the first dose. Gd-EOB-DTPA-enhanced MRI scan was performed after 24 hours,and after injection of the contrast agent Gd-EOB-DTPA( 0. 15 ml/kg body weight),the signal values of high-,medium-,and low-signal regions were measured during plain scan and at 20 and 26 minutes of MRI scan. Liver puncture was performed in different signal regions. Gd-EOB-DTPA-enhanced MRI was performed for the control group,and liver puncture was performed in the corresponding regions. HE staining and electron microscopy were used for tissue examination,and the two groups were compared in terms of signal values and the results of HE staining and electron microscopy. The independent samples t-test was used for comparison of continuous data at each time point between the two groups,and an analysis of variance with repeated measures was used for comparison at different time points within groups; a one-way analysis of variance was used for comparison of signal values at each time point within groups. Results The ALF group had high,medium,and low signals in different time periods after Gd-EOB-DTPA-enhanced MRI scan,and HE staining and electron microscopy showed varying degrees of hepatocyte injury in the high-,medium-,and low-signal regions. The ALF group had significant differences in the levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin at 0,6,12,and 24 hours( F = 54. 909,148. 238,and 11. 778,all P < 0. 01). In the ALF group and the control group,the high-,medium-,and low-signal values showed significant changes during plain scan and at 20 and 26 minutes of MRI scan( ALF group: F = 232. 69,65. 39,and 24. 91,all P < 0. 01; control group: F = 800. 43,817. 35,and 795. 71,all P < 0. 01). In the ALF group,there were significant differences in the high-,medium-,and low-signal values during plain scan and at 20 and 26 minutes of MRI scan( F = 3. 914,24. 343,and 22. 424,all P < 0. 05). There were significant differences between the two groups in the medium-and low-signal values at 20 minutes of MRI scan( t =-7. 813 and-7. 492,both P < 0. 001) and the high-,medium-,and low-signal values at 26 minutes of MRI scan( t =-3. 075,-4. 785,and-6. 326,P =0. 008,P < 0. 001,and P < 0. 001). The reduction in corresponding signals was associated with the degree of hepatocyte injury. Conclusion Gd-EOB-DTPA-enhanced MRI scan is feasible for the assessment of liver function in ALF dogs,and it can also predict the degree of liver pathological damage.
引文
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[10]NASSIF A,JIA J,KEISER M,et al.Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging[J].Radiology,2012,264(3):741-750.
[11]WANG L,COLLINS C,KELLY EJ,et al.Transporter expression in liver tissue from subjects with alcoholic or hepatitis Ccirrhosis quantified by targeted quantitative proteomics[J].Drug Metab Dispos,2016,44(11):1752-1758.
[12]MARKS AL,HECHT S,STOKES JE,et al.Effects of gadoxetate disodium(Eovist1)contrast on magnetic resonance imaging characteristics of the liver in clinically healthy dogs[J].Vet Radiol Ultrasound,2014,55(3):286-291.
[13]MA KS,JIANG JY.Application of tissue-specific magnetic resonance imaging contrast agent gadolinium ethoxybenzyl dimeglumine on precision hepatic surgery[J].Chin J Dig Surg,2017,16(2):124-129.(in Chinese)马宽生,蒋家云.钆塞酸二钠增强MRI检查在精准肝脏外科中的应用[J].中华消化外科杂志,2017,16(2):124-129.
[14]DAHLQVIST LEINHARD O,DAHLSTROM N,KIHLBERG J,et al.Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA:A pilot study[J].Eur Radiol,2012,22(3):642-653.
[15]NIKLAS V,KIRSTEN U,FLORIAN Z,et al.Diagnostic performance of Gd-EOB-DTPA-enhanced MRI for evaluation of liver dysfunction:A multivariable analysis of 3T MRI sequences[J].Oncotarget,2018,9(91):36371-36378.
[16]BORUSEWICZ P,STANCZYK E,KUBIAK K,et al.Liver enhancement in healthy dogs after gadoxetic acid administration during dynamic contrast-enhanced magnetic resonance imaging[J].Vet J,2018,235:16-21.
[17]KATSUBE T,OKADA M,KUMANO S,et al.Estimation of liver function using T1 mapping on Gd-EOB-DTPA enhanced magnetic resonance imaging[J].Investig Radiol,2011,46(4):277-283.
[2]HOU HX,ZHAO L,JIANG XM,et al.Early continuous venovenous hemodiafiltration combined with hemoperfusion for successful treatment of acute liver failure and hepatic encephalopathy caused by mushroom poisoning:A report of 2 cases[J].JClin Hepatol,2018,34(12):2655-2658.(in Chinese)侯洪翔,赵亮,姜晓明,等.早期连续性静脉-静脉血液透析滤过联合血液灌流成功救治毒覃中毒致急性肝衰竭、肝性脑病2例报告[J].临床肝胆病杂志,2018,34(12):2655-2658.
[3]LARSEN FS,SCHMIDT LE,BEMSMEIER C,et al.High-volume plasma exchange in patients with acute liver failure:An open randomized controlled trial[J].J Hepatol,2016,64(1):69-78.
[4]DING Y,ZENG MS.Clinical application of liver-specific contrast agent Gd+-EOB-DTPA in progression assessment and early diagnosis of hepatocellular carcinoma[J].J Clin Hepatol,2013,29(10):736-739.(in Chinese)丁莺,曾蒙苏.普美显在肝硬化结节多步癌变及肝细胞癌早期诊断中的应用[J].临床肝胆病杂志,2013,29(10):736-739.
[5]KAMIMURA K,FUKUKURA Y,YONEYAMA T,et al.Quantitative evaluation of liver function with T1 relaxation time index on Gd-EOB-DTPA enhanced MRI:Comparison with signal intensitybased indices[J].J Magn Reson Imaging,2014,40(4):884-889.
[6]HUANG JW,YIN LH.Establishment of a dog model of carbon tetrachloride-induced acute liver failure[J].Guangdong Med J,2010,31(17):2249-2250.(in Chinese)黄建伟,尹良红.四氯化碳诱导犬急性肝功能衰竭模型的建立[J].广东医学,2010,31(17):2249-2250.
[7]CUI SY,XING WH,LIU L,et al.The value of CT combined with enhanced scan in the stage diagnosis of liver failure[J].Chin J CT and MRI,2016,14(9):71-73.(in Chinese)崔树彦,邢卫红,刘莲,等.CT平扫与增强扫描在肝衰竭分期诊断中的价值分析[J].中国CT和MRI杂志,2016,14(9):71-73.
[8]HAIMERL M,SCHLABECK M,VERLOH N,et al.Volume-assisted estimation of liver function based on Gd-EOB-DTPA-enhanced MR relaxometry[J].Eur Radiol,2016,26(4):1125-1133.
[9]WANG JD,LENG J,YANG YL,et al.Factors for adverse effects of four gadolinium contrast agents and related countermeasures[J].Chin J Clin Pharmacol Ther,2018,23(9):1056-1062.(in Chinese)王军大,冷静,杨雅淋,等.四种钆对比剂不良反应相关因素分析及处理方式[J].中国临床药理学与治疗学,2018,23(9):1056-1062.
[10]NASSIF A,JIA J,KEISER M,et al.Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging[J].Radiology,2012,264(3):741-750.
[11]WANG L,COLLINS C,KELLY EJ,et al.Transporter expression in liver tissue from subjects with alcoholic or hepatitis Ccirrhosis quantified by targeted quantitative proteomics[J].Drug Metab Dispos,2016,44(11):1752-1758.
[12]MARKS AL,HECHT S,STOKES JE,et al.Effects of gadoxetate disodium(Eovist1)contrast on magnetic resonance imaging characteristics of the liver in clinically healthy dogs[J].Vet Radiol Ultrasound,2014,55(3):286-291.
[13]MA KS,JIANG JY.Application of tissue-specific magnetic resonance imaging contrast agent gadolinium ethoxybenzyl dimeglumine on precision hepatic surgery[J].Chin J Dig Surg,2017,16(2):124-129.(in Chinese)马宽生,蒋家云.钆塞酸二钠增强MRI检查在精准肝脏外科中的应用[J].中华消化外科杂志,2017,16(2):124-129.
[14]DAHLQVIST LEINHARD O,DAHLSTROM N,KIHLBERG J,et al.Quantifying differences in hepatic uptake of the liver specific contrast agents Gd-EOB-DTPA and Gd-BOPTA:A pilot study[J].Eur Radiol,2012,22(3):642-653.
[15]NIKLAS V,KIRSTEN U,FLORIAN Z,et al.Diagnostic performance of Gd-EOB-DTPA-enhanced MRI for evaluation of liver dysfunction:A multivariable analysis of 3T MRI sequences[J].Oncotarget,2018,9(91):36371-36378.
[16]BORUSEWICZ P,STANCZYK E,KUBIAK K,et al.Liver enhancement in healthy dogs after gadoxetic acid administration during dynamic contrast-enhanced magnetic resonance imaging[J].Vet J,2018,235:16-21.
[17]KATSUBE T,OKADA M,KUMANO S,et al.Estimation of liver function using T1 mapping on Gd-EOB-DTPA enhanced magnetic resonance imaging[J].Investig Radiol,2011,46(4):277-283.