Gd-EOB-DTPA MRI在监测肝硬化结节多步态癌变早期中的应用进展
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摘要
肝癌在肝硬化背景下发生发展是一个多步态过程,这一过程处于相邻阶段的高级退变结节及早期肝癌具有发展为下一阶段肝癌的高风险性,因此早期发现并准确诊断高危患者的这些结节具有重要意义。钆塞酸二钠(Gd-EOB-DTPA,Primovist)是一种肝脏特异性磁共振对比剂,因具有细胞内外双重对比剂效应,从而能更多地检出肝脏小病灶(<2 cm,尤其是<1 cm)并具有较高的定性诊断准确率,这有利于肝癌的早期发现及有效治疗从而延长患者生存时间及提高患者生存质量。本文旨在总结回顾并重点阐述退变结节及早期肝癌在动态演变过程中,其相应微观病理及功能改变,可通过GdEOB-DTPA联合其他MRI序列应用予以识别观测,用于肝硬化相关结节的鉴别诊断及其转归评价。
Hepatocellular carcinoma, based on liver cirrhosis, develops via the multistep process of hepatocarcinogenesis. Dysplastic nodule and early HCC, which are at the adjacent stages in the process, are in the high risk for transformation into advanced HCC, thus it is important for these nodules to be early detected and accurately diagnosed. Gd-EOB-DTPA is a hepatocyte specific magnetic resonance imaging contrast agent. It has demonstrated an increased ability of Gd-EOB-DTPA for the detection and higher accurate qualitative diagnosis rate of small liver lesions(<2 cm, especially<1 cm) due to its dual performance-extracellular and intracellular contrast agent performance. It benefits early detection of HCC and provides more treatment options with better effectiveness, consequently, prolongs the patient's survival expectancy and improves the patient's survival quality. The article aims to summarize, review and focus on the corresponding microscopic pathological and functional changes in the dynamic evolution process of dysplastic nodules and early hepatocellular carcinoma, which can be identified and observed by combining Gd-EOB-DTPA with other MRI sequences for the differential diagnosis and outcome evaluation of liver cirrhosis-associated nodules.
Hepatocellular carcinoma, based on liver cirrhosis, develops via the multistep process of hepatocarcinogenesis. Dysplastic nodule and early HCC, which are at the adjacent stages in the process, are in the high risk for transformation into advanced HCC, thus it is important for these nodules to be early detected and accurately diagnosed. Gd-EOB-DTPA is a hepatocyte specific magnetic resonance imaging contrast agent. It has demonstrated an increased ability of Gd-EOB-DTPA for the detection and higher accurate qualitative diagnosis rate of small liver lesions(<2 cm, especially<1 cm) due to its dual performance-extracellular and intracellular contrast agent performance. It benefits early detection of HCC and provides more treatment options with better effectiveness, consequently, prolongs the patient's survival expectancy and improves the patient's survival quality. The article aims to summarize, review and focus on the corresponding microscopic pathological and functional changes in the dynamic evolution process of dysplastic nodules and early hepatocellular carcinoma, which can be identified and observed by combining Gd-EOB-DTPA with other MRI sequences for the differential diagnosis and outcome evaluation of liver cirrhosis-associated nodules.
引文
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[6]Duncan JK,Ma N,Vreugdenburg TD,et al.Gadoxetic acid-enhanced MRI for the characterization of hepatocellular carcinoma:A systematic review and Meta-analysis.J Magn Reson Imaging,2017,45(1):281-290.
[7]Kim BR,Lee JM,Lee DH,et al.Diagnostic performance of gadoxetic acid-enhanced liver MR imaging versus multidetector CT in the detection of dysplastic nodules and early hepatocellular carcinoma.Radiology,2017,285(1):134-146.
[8]Renzulli M,Biselli M,Brocchi S,et al.New hallmark of hepatocellular carcinoma,early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis:A new diagnostic algorithm.Gut,2018,67(9):1674-1682.
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[10]Kojiro M.Pathological diagnosis at early stage:Reaching international consensus.Oncology,2010,78(Suppl 1):31-35.
[11]Choi JY,Lee JM,Sirlin CB.CT and MR imaging diagnosis and staging of hepatocellular carcinoma:part I.Development,growth,and spread:key pathologic and imaging aspects.Radiology,2014,272(3):635-654.
[12]Ichikawa T,Sano K,Morisaka H.Diagnosis of pathologically early HCC with EOB-MRI:Experiences and current consensus.Liver Cancer,2014,3(2):97-107.
[13]Gheonea IA,Streba CT,Cristea CG,et al.MRI and pathology aspects of hypervascular nodules in cirrhotic liver:from dysplasia to hepatocarcinoma.Rom J Morphol Embryol,2015,56(3):925-935.
[14]Scali EP,Walshe T,Tiwari HA,et al.A pictorial review of hepatobiliary magnetic resonance imaging with hepatocyte-specific contrast agents:Uses,findings,and pitfalls of gadoxetate disodium and gadobenate dimeglumine.Can Assoc Radiol J,2017,68(3):293-307.
[15]Li RK,Zeng MS,Qiang JW,et al.Improving detection of iron deposition in cirrhotic liver using susceptibility-weighted imaging with emphasis on histopathological correlation.J Comput Assist Tomogr,2017,41(1):18-24.
[16]Yang WH,Liu HY,Zhang XH,et al.The clinical application of magnetic sensitive weighted imaging in liver cirrhosis nodules multistep canceration.J Med Imaging,2017,27(6):1112-1118.杨文海,刘红宇,张雪红,等.磁敏感加权成像在肝硬化结节多步癌变中的临床应用.医学影像学杂志,2017,27(6):1112-1118.
[17]Inchingolo R,De Gaetano AM,Curione D,et al.Role of diffusionweighted imaging,apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver.Eur Radiol,2015,25(4):1087-1096.
[18]Hwang J,Kim YK,Jeong WK,et al.Nonhypervascular hypointense nodules at gadoxetic acid-enhanced MR imaging in chronic liver disease:Diffusion-weighted imaging for characterization.Radiology,2015,276(1):137-146.
[19]Zhu SC,Liu YH,Wei Y,et al.Intravoxel incoherent motion diffusionweighted magnetic resonance imaging for predicting histological grade of hepatocellular carcinoma:Comparison with conventional diffusionweighted imaging.World J Gastroenterol,2018,24(8):929-940.
[20]Bartolozzi C,Battaglia V,Bargellini I,et al.Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis:correlation with histological findings on explanted livers.Abdom Imaging,2013,38(2):290-296.
[21]Channual S,Tan N,Siripongsakun S,et al.Gadoxetate disodiumenhanced MRI to differentiate dysplastic nodules and grade of hepatocellular carcinoma:Correlation with histopathology.AJR Am JRoentgenol,2015,205(3):546-553.
[22]Qin XL,Huang ZK,Long LL,et al.The value of gadoliniumethoxybenzyldiethylenetriamine pentaacetic acid enhanced T1 mapping in dysplastic nodule and hepatocellular carcinoma with different degrees of differentiation.Chin J Radiol,2018,52(8):603-607.覃夏丽,黄仲奎,龙莉玲,等.钆塞酸二钠增强MRI T1mapping鉴别诊断不典型增生结节及不同分化程度肝细胞癌的价值.中华放射学杂志,2018,52(8):603-607.
[23]Chen J,Chen C,Xia C,et al.Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid:correlations with Ki67 proliferation status,histological grades,and microvascular density.Abdom Radiol(NY),2018,43(6):1393-1403.
[24]Yoon JH,Lee JM,Yu MH,et al.Evaluation of hepatic focal lesions using diffusion-weighted MR imaging:comparison of apparent diffusion coefficient and intravoxel incoherent motion-derived parameters.J Magn Reson Imaging,2014,39(2):276-285.
[22]Bartolozzi C,Battaglia V,Bargellini I,et al.Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis:correlation with histological findings on explanted livers.Abdom Imaging,2013,38(2):290-296.
[23]Kitao A,Matsui O,Yoneda N,et al.The uptake transporter OATP8expression decreases during multistep hepatocarcinogenesis:correlation with gadoxetic acid enhanced MR imaging.Eur Radiol,2011,21(10):2056-2066.
[24]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[25]Min JH,Kim YK,Kang TW,et al.Artifacts during the arterial phase of gadoxetate disodium-enhanced MRI:Multiple arterial phases using view-sharing from two different vendors versus single arterial phase imaging.Eur Radiol,2018,28(8):3335-3346.
[26]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid-enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[27]Suh CH,Kim KW,Pyo J,et al.Hypervascular transformation of hypovascular hypointense nodules in the hepatobiliary phase of gadoxetic acid-enhanced MRI:A systematic review and meta-analysis.AJR Am J Roentgenol,2017,209(4):781-789.
[28]Kim YS,Song JS,Lee HK,et al.Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acidenhanced MR images in patients with chronic liver disease:long-term outcomes and risk factors for hypervascular transformation.Eur Radiol,2016,26(10):3728-3736.
[29]Cho YK,Kim JW,Kim MY,et al.Non-hypervascular hypointense nodules on hepatocyte phaseGadoxetic acid-Enhanced MR images:Transformation of MR hepatobiliary hypointense nodules into hypervascular hepatocellular carcinomas.Gut Liver,2018,12(1):79-85.
[30]Higaki A,Ito K,Tamada T,et al.High-risk nodules detected in the hepatobiliary phase of Gd-EOB-DTPA-enhanced mr imaging in cirrhosis or chronic hepatitis:Incidence and predictive factors for hypervascular transformation,preliminary results.J Magn Reson Imaging,2013,37(6):1377-1383.
[31]Yang HJ,Song JS,Choi EJ,et al.Hypovascular hypointense nodules in hepatobiliary phase without T2 hyperintensity:long-term outcomes and added value of DWI in predicting hypervascular transformation.Clin Imaging,2018,50:123-129.
[32]Chou CT,Chou JM,Chang TA,et al.Differentiation between dysplastic nodule and early-stage hepatocellular carcinoma:The utility of conventional MR imaging.World J Gastroenterol,2013,19(42):7433-7439.
[33]Toyoda H,Kumada T,Tada T,et al.Non-hypervascular hypointense nodules detected by Gd-EOBDTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.J Hepatol,2013,58(6):1174-1180.
[34]Lee DH,Lee JM,Lee JY,et al.Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI:Risk of HCC recurrence after radiofrequency ablation.J Hepatol,2015,62(5):1122-1130.
[35]Van Beers BE,Pastor CM,Hussain HK.Primovist,eovist:What to expect?.J Hepatol,2012,57(2):421-429.
[36]Sciarra A,Schmidt S,Pellegrinelli A,et al.OATPB1/B3 and MRP3expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy.Liver Int,2019,39(1):158-167.
[37]Kitao A,Zen Y,Matsui O,et al.Hepatocellular carcinoma:signal intensity at gadoxetic acid-enhanced MR imaging-correlation with molecular transporters and histopathologic features.Radiology,2010,256(3):817-826.
[38]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid-enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[39]Tsuboyama T,Onishi H,Kim T,et al.Hepatocellular carcinoma:hepatocyte-selective enhancement at gadoxetic acid-enhanced MRimaging-correlation with expression of sinusoidal and canalicular transporters and bile accumulation.Radiology,2010,255(3):824-833.
[40]Sano K,Ichikawa T,Motosugi U,et al.Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis.Eur Radiol,2017,27(2):518-525.
[41]Matsuda M,Tsuda T,Yoshioka S,et al.Incidence for progression of hypervascular HCC in hypovascular hepatic nodules showing hyperintensity on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver diseases.Jpn J Radiol,2014,32(7):405-413.
[2]Park HJ,Choi BI,Lee ES,et al.How to differentiate borderline hepatic nodules in hepatocarcinogenesis:Emphasis on imaging diagnosis.Liver Cancer,2017,6(3):189-203.
[3]Choi BI,Lee JM,Kim TK,et al.Diagnosing borderline hepatic nodules in hepatocarcinogenesis:imaging performance.AJR Am J Roentgenol,2015,205(1):10-21.
[4]Inchingolo R,Faletti R,Grazioli L,et al.MR with Gd-EOB-DTPA in assessment of liver nodules in cirrhotic patients.World J Hepatol,2018,10(7):462-473.
[5]Lee YJ,Lee JM,Lee JS,et al.Hepatocellular carcinoma:Diagnostic performance of multidetector CT and MR imaging-A systematic review and meta-analysis.Radiology,2015,275(1):97-109.
[6]Duncan JK,Ma N,Vreugdenburg TD,et al.Gadoxetic acid-enhanced MRI for the characterization of hepatocellular carcinoma:A systematic review and Meta-analysis.J Magn Reson Imaging,2017,45(1):281-290.
[7]Kim BR,Lee JM,Lee DH,et al.Diagnostic performance of gadoxetic acid-enhanced liver MR imaging versus multidetector CT in the detection of dysplastic nodules and early hepatocellular carcinoma.Radiology,2017,285(1):134-146.
[8]Renzulli M,Biselli M,Brocchi S,et al.New hallmark of hepatocellular carcinoma,early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis:A new diagnostic algorithm.Gut,2018,67(9):1674-1682.
[9]The International Consensus Group for Hepatocellular Neoplasia.Pathologic diagnosis of early hepatocellular carcinoma:A report of The International Consensus Group for Hepatocellular Neoplasia.Hepatology,2009,49(2):658-664.
[10]Kojiro M.Pathological diagnosis at early stage:Reaching international consensus.Oncology,2010,78(Suppl 1):31-35.
[11]Choi JY,Lee JM,Sirlin CB.CT and MR imaging diagnosis and staging of hepatocellular carcinoma:part I.Development,growth,and spread:key pathologic and imaging aspects.Radiology,2014,272(3):635-654.
[12]Ichikawa T,Sano K,Morisaka H.Diagnosis of pathologically early HCC with EOB-MRI:Experiences and current consensus.Liver Cancer,2014,3(2):97-107.
[13]Gheonea IA,Streba CT,Cristea CG,et al.MRI and pathology aspects of hypervascular nodules in cirrhotic liver:from dysplasia to hepatocarcinoma.Rom J Morphol Embryol,2015,56(3):925-935.
[14]Scali EP,Walshe T,Tiwari HA,et al.A pictorial review of hepatobiliary magnetic resonance imaging with hepatocyte-specific contrast agents:Uses,findings,and pitfalls of gadoxetate disodium and gadobenate dimeglumine.Can Assoc Radiol J,2017,68(3):293-307.
[15]Li RK,Zeng MS,Qiang JW,et al.Improving detection of iron deposition in cirrhotic liver using susceptibility-weighted imaging with emphasis on histopathological correlation.J Comput Assist Tomogr,2017,41(1):18-24.
[16]Yang WH,Liu HY,Zhang XH,et al.The clinical application of magnetic sensitive weighted imaging in liver cirrhosis nodules multistep canceration.J Med Imaging,2017,27(6):1112-1118.杨文海,刘红宇,张雪红,等.磁敏感加权成像在肝硬化结节多步癌变中的临床应用.医学影像学杂志,2017,27(6):1112-1118.
[17]Inchingolo R,De Gaetano AM,Curione D,et al.Role of diffusionweighted imaging,apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver.Eur Radiol,2015,25(4):1087-1096.
[18]Hwang J,Kim YK,Jeong WK,et al.Nonhypervascular hypointense nodules at gadoxetic acid-enhanced MR imaging in chronic liver disease:Diffusion-weighted imaging for characterization.Radiology,2015,276(1):137-146.
[19]Zhu SC,Liu YH,Wei Y,et al.Intravoxel incoherent motion diffusionweighted magnetic resonance imaging for predicting histological grade of hepatocellular carcinoma:Comparison with conventional diffusionweighted imaging.World J Gastroenterol,2018,24(8):929-940.
[20]Bartolozzi C,Battaglia V,Bargellini I,et al.Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis:correlation with histological findings on explanted livers.Abdom Imaging,2013,38(2):290-296.
[21]Channual S,Tan N,Siripongsakun S,et al.Gadoxetate disodiumenhanced MRI to differentiate dysplastic nodules and grade of hepatocellular carcinoma:Correlation with histopathology.AJR Am JRoentgenol,2015,205(3):546-553.
[22]Qin XL,Huang ZK,Long LL,et al.The value of gadoliniumethoxybenzyldiethylenetriamine pentaacetic acid enhanced T1 mapping in dysplastic nodule and hepatocellular carcinoma with different degrees of differentiation.Chin J Radiol,2018,52(8):603-607.覃夏丽,黄仲奎,龙莉玲,等.钆塞酸二钠增强MRI T1mapping鉴别诊断不典型增生结节及不同分化程度肝细胞癌的价值.中华放射学杂志,2018,52(8):603-607.
[23]Chen J,Chen C,Xia C,et al.Quantitative free-breathing dynamic contrast-enhanced MRI in hepatocellular carcinoma using gadoxetic acid:correlations with Ki67 proliferation status,histological grades,and microvascular density.Abdom Radiol(NY),2018,43(6):1393-1403.
[24]Yoon JH,Lee JM,Yu MH,et al.Evaluation of hepatic focal lesions using diffusion-weighted MR imaging:comparison of apparent diffusion coefficient and intravoxel incoherent motion-derived parameters.J Magn Reson Imaging,2014,39(2):276-285.
[22]Bartolozzi C,Battaglia V,Bargellini I,et al.Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis:correlation with histological findings on explanted livers.Abdom Imaging,2013,38(2):290-296.
[23]Kitao A,Matsui O,Yoneda N,et al.The uptake transporter OATP8expression decreases during multistep hepatocarcinogenesis:correlation with gadoxetic acid enhanced MR imaging.Eur Radiol,2011,21(10):2056-2066.
[24]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[25]Min JH,Kim YK,Kang TW,et al.Artifacts during the arterial phase of gadoxetate disodium-enhanced MRI:Multiple arterial phases using view-sharing from two different vendors versus single arterial phase imaging.Eur Radiol,2018,28(8):3335-3346.
[26]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid-enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[27]Suh CH,Kim KW,Pyo J,et al.Hypervascular transformation of hypovascular hypointense nodules in the hepatobiliary phase of gadoxetic acid-enhanced MRI:A systematic review and meta-analysis.AJR Am J Roentgenol,2017,209(4):781-789.
[28]Kim YS,Song JS,Lee HK,et al.Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acidenhanced MR images in patients with chronic liver disease:long-term outcomes and risk factors for hypervascular transformation.Eur Radiol,2016,26(10):3728-3736.
[29]Cho YK,Kim JW,Kim MY,et al.Non-hypervascular hypointense nodules on hepatocyte phaseGadoxetic acid-Enhanced MR images:Transformation of MR hepatobiliary hypointense nodules into hypervascular hepatocellular carcinomas.Gut Liver,2018,12(1):79-85.
[30]Higaki A,Ito K,Tamada T,et al.High-risk nodules detected in the hepatobiliary phase of Gd-EOB-DTPA-enhanced mr imaging in cirrhosis or chronic hepatitis:Incidence and predictive factors for hypervascular transformation,preliminary results.J Magn Reson Imaging,2013,37(6):1377-1383.
[31]Yang HJ,Song JS,Choi EJ,et al.Hypovascular hypointense nodules in hepatobiliary phase without T2 hyperintensity:long-term outcomes and added value of DWI in predicting hypervascular transformation.Clin Imaging,2018,50:123-129.
[32]Chou CT,Chou JM,Chang TA,et al.Differentiation between dysplastic nodule and early-stage hepatocellular carcinoma:The utility of conventional MR imaging.World J Gastroenterol,2013,19(42):7433-7439.
[33]Toyoda H,Kumada T,Tada T,et al.Non-hypervascular hypointense nodules detected by Gd-EOBDTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy.J Hepatol,2013,58(6):1174-1180.
[34]Lee DH,Lee JM,Lee JY,et al.Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI:Risk of HCC recurrence after radiofrequency ablation.J Hepatol,2015,62(5):1122-1130.
[35]Van Beers BE,Pastor CM,Hussain HK.Primovist,eovist:What to expect?.J Hepatol,2012,57(2):421-429.
[36]Sciarra A,Schmidt S,Pellegrinelli A,et al.OATPB1/B3 and MRP3expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy.Liver Int,2019,39(1):158-167.
[37]Kitao A,Zen Y,Matsui O,et al.Hepatocellular carcinoma:signal intensity at gadoxetic acid-enhanced MR imaging-correlation with molecular transporters and histopathologic features.Radiology,2010,256(3):817-826.
[38]Erra P,Puglia M,Ragozzino A,et al.Appearance of hepatocellular carcinoma on gadoxetic acid-enhanced hepato-biliary phase MRimaging:a systematic review.Radiol Med,2015,120(11):1002-1011.
[39]Tsuboyama T,Onishi H,Kim T,et al.Hepatocellular carcinoma:hepatocyte-selective enhancement at gadoxetic acid-enhanced MRimaging-correlation with expression of sinusoidal and canalicular transporters and bile accumulation.Radiology,2010,255(3):824-833.
[40]Sano K,Ichikawa T,Motosugi U,et al.Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis.Eur Radiol,2017,27(2):518-525.
[41]Matsuda M,Tsuda T,Yoshioka S,et al.Incidence for progression of hypervascular HCC in hypovascular hepatic nodules showing hyperintensity on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver diseases.Jpn J Radiol,2014,32(7):405-413.