DOI QR코드

DOI QR Code

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology

  • Woo Kyoung Jeong (Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hyo-Jin Kang (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Sang Hyun Choi (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Mi-Suk Park (Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine) ;
  • Mi Hye Yu (Department of Radiology, Konkuk University Hospital, Konkuk University College of Medicine) ;
  • Bohyun Kim (Department of Radiology, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea) ;
  • Myung-Won You (Department of Radiology, Kyung Hee University Hospital, Kyung Hee University College of Medicine) ;
  • Sanghyeok Lim (Department of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Young Seo Cho (Department of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine) ;
  • Min Woo Lee (Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeong Ah Hwang (Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jae Young Lee (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jung Hoon Kim (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Ijin Joo (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • Jae Seok Bae (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine) ;
  • So Yeon Kim (Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yong Eun Chung (Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine) ;
  • Dong Hwan Kim (Department of Radiology, Seoul St. Mary Hospital, College of Medicine, The Catholic University of Korea) ;
  • Jeong Min Lee (Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine)
  • Received : 2023.04.07
  • Accepted : 2023.04.11
  • Published : 2023.06.01

Abstract

Sonazoid, a second-generation ultrasound contrast agent, was introduced for the diagnosis of hepatic nodules. To clarify the issues with Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma (HCC), the Korean Society of Radiology and Korean Society of Abdominal Radiology collaborated on the guidelines. The guidelines are de novo, evidence-based, and selected using an electronic voting system for consensus. These include imaging protocols, diagnostic criteria for HCC, diagnostic value for lesions that are inconclusive on other imaging results, differentiation from non-HCC malignancies, surveillance of HCC, and treatment response after locoregional and systemic treatment for HCC.

Keywords

Acknowledgement

The authors would like to thank Dr. Mi Young Choi (National Evidence-based Healthcare Collaborating Agency, Korea), Chang Hee Cho (The Korean Society of Radiology, Korea) and Euisoo Shin (University of Ulsan College of Medicine, Asan Medical Library, Korea) for consulting on the evidence search and guideline development process.

References

  1. Frinking P, Segers T, Luan Y, Tranquart F. Three decades of ultrasound contrast agents: a review of the past, present and future improvements. Ultrasound Med Biol 2020;46:892-908 https://doi.org/10.1016/j.ultrasmedbio.2019.12.008
  2. Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, et al. The AFSUMB consensus statements and recommendations for the clinical practice of contrast-enhanced ultrasound using Sonazoid. Ultrasonography 2020;39:191-220 https://doi.org/10.14366/usg.20057
  3. Yang Y, Liu C, Yan J, Liu K. Perfluorobutane contrast-enhanced ultrasonography for the diagnosis of HCC: a systematic review and meta-analysis. Abdom Radiol (NY) 2021;46:4619-4628 https://doi.org/10.1007/s00261-021-03141-5
  4. Centre for Evidence-based Medicine (CEBM). Oxford Centre for Evidence-Based Medicine: Levels of Evidence. University of Oxford.com https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009. Published March, 2009. Accessed Aug 30, 2022
  5. Dietrich CF, Nolsee CP, Barr RG, Berzigotti A, Burns PN, Cantisani V, et al. Guidelines and good clinical practice recommendations for contrast-enhanced ultrasound (CEUS) in the liver-update 2020 WFUMB in cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultrasound Med Biol 2020;46:2579-2604 https://doi.org/10.1016/j.ultrasmedbio.2020.04.030
  6. Shunichi S, Hiroko I, Fuminori M, Waki H. Definition of contrast enhancement phases of the liver using a perfluoro-based microbubble agent, perflubutane microbubbles. Ultrasound Med Biol 2009;35:1819-1827 https://doi.org/10.1016/j.ultrasmedbio.2009.05.013
  7. Kang HJ, Kim JH, Yoo J, Han JK. Diagnostic criteria of perfluorobutane-enhanced ultrasonography for diagnosing hepatocellular carcinoma in high-risk individuals: how is late washout determined? Ultrasonography 2022;41:530-542 https://doi.org/10.14366/usg.21172
  8. 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;272:635-654 https://doi.org/10.1148/radiol.14132361
  9. Korean Liver Cancer Association (KLCA); National Cancer Center (NCC), Goyang, Korea. 2018 Korean Liver Cancer Association-National Cancer Center Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 2019;20:1042-1113 https://doi.org/10.3348/kjr.2019.0140
  10. Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, et al. Liver imaging reporting and data system (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology 2018;289:816-830 https://doi.org/10.1148/radiol.2018181494
  11. Korean Liver Cancer Association (KLCA), National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 2022;23:1126-1240 https://doi.org/10.3348/kjr.2022.0822
  12. Joo I, Lee JM, Koh YH, Choi SH, Lee S, Chung JW. 2022 Korean Liver Cancer Association-National Cancer Center Korea practice guidelines for imaging diagnosis of hepatocellular carcinoma: what's new? Korean J Radiol 2023;24:1-5 https://doi.org/10.3348/kjr.2022.0538
  13. Hwang JA, Jeong WK, Min JH, Kim YY, Heo NH, Lim HK. Sonazoid-enhanced ultrasonography: comparison with CT/MRI Liver Imaging Reporting and Data System in patients with suspected hepatocellular carcinoma. Ultrasonography 2021;40:486-498 https://doi.org/10.14366/usg.20120
  14. Kang HJ, Lee JM, Yoon JH, Lee K, Kim H, Han JK. Contrast-enhanced US with sulfur hexafluoride and perfluorobutane for the diagnosis of hepatocellular carcinoma in individuals with high risk. Radiology 2020;297:108-116 https://doi.org/10.1148/radiol.2020200115
  15. Vilana R, Forner A, Bianchi L, Garcia-Criado A, Rimola J, de Lope CR, et al. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 2010;51:2020-2029 https://doi.org/10.1002/hep.23600
  16. Han J, Liu Y, Han F, Li Q, Yan C, Zheng W, et al. The degree of contrast washout on contrast-enhanced ultrasound in distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma. Ultrasound Med Biol 2015;41:3088-3095 https://doi.org/10.1016/j.ultrasmedbio.2015.08.001
  17. Wildner D, Bernatik T, Greis C, Seitz K, Neurath MF, Strobel D. CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients - early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med 2015;36:132-139 https://doi.org/10.1055/s-0034-1399147
  18. Zhang HC, Zhu T, Hu RF, Wu L. Contrast-enhanced ultrasound imaging features and clinical characteristics of combined hepatocellular cholangiocarcinoma: comparison with hepatocellular carcinoma and cholangiocarcinoma. Ultrasonography 2020;39:356-366 https://doi.org/10.14366/usg.19093
  19. Yang HK, Burns PN, Jang HJ, Kono Y, Khalili K, Wilson SR, et al. Contrast-enhanced ultrasound approach to the diagnosis of focal liver lesions: the importance of washout. Ultrasonography 2019;38:289-301 https://doi.org/10.14366/usg.19006
  20. Terzi E, Iavarone M, Pompili M, Veronese L, Cabibbo G, Fraquelli M, et al. Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1,006 nodules. J Hepatol 2018;68:485-492 https://doi.org/10.1016/j.jhep.2017.11.007
  21. Saito A, Yamamoto M, Katagiri S, Yamashita S, Nakano M, Morizane T. Early hemodynamics of hepatocellular carcinoma using contrast-enhanced ultrasound with Sonazoid: focus on the pure arterial and early portal phases. Glob Health Med 2020;2:319-327 https://doi.org/10.35772/ghm.2020.01092
  22. Kudo M, Hatanaka K, Inoue T, Maekawa K. Depiction of portal supply in early hepatocellular carcinoma and dysplastic nodule: value of pure arterial ultrasound imaging in hepatocellular carcinoma. Oncology 2010;78 Suppl 1:60-67 https://doi.org/10.1159/000315232
  23. Takahashi M, Maruyama H, Ishibashi H, Yoshikawa M, Yokosuka O. Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma. AJR Am J Roentgenol 2011;196:W123-W131 https://doi.org/10.2214/AJR.10.4242
  24. Hwang JA, Jeong WK, Kang HJ, Lee ES, Park HJ, Lee JM. Perfluorobutane-enhanced ultrasonography with a Kupffer phase: improved diagnostic sensitivity for hepatocellular carcinoma. Eur Radiol 2022;32:8507-8517 https://doi.org/10.1007/s00330-022-08900-6
  25. Inoue T, Kudo M, Hatanaka K, Takahashi S, Kitai S, Ueda T, et al. Imaging of hepatocellular carcinoma: qualitative and quantitative analysis of postvascular phase contrast-enhanced ultrasonography with Sonazoid. Comparison with superparamagnetic iron oxide magnetic resonance images. Oncology 2008;75 Suppl 1:48-54 https://doi.org/10.1159/000173424
  26. Yang WY, Park HS, Kim YJ, Yu MH, Jung SI, Jeon HJ. Visibility of focal liver lesions: comparison between Kupffer phase of CEUS with Sonazoid and hepatobiliary phase of gadoxetic acid-enhanced MRI. J Clin Ultrasound 2017;45:542-550 https://doi.org/10.1002/jcu.22499
  27. Sugimoto K, Kakegawa T, Takahashi H, Tomita Y, Abe M, Yoshimasu Y, et al. Usefulness of modified CEUS LI-RADS for the diagnosis of hepatocellular carcinoma using Sonazoid. Diagnostics (Basel) 2020;10:828
  28. American College of Radiology (ACR). CEUS LI-RADS(R) v2017. ACR Website. https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/LI-RADS/LI-RADS-CEUS-v2017. Accessed March 31, 2023
  29. Alaboudy A, Inoue T, Hatanaka K, Chung H, Hyodo T, Kumano S, et al. Usefulness of combination of imaging modalities in the diagnosis of hepatocellular carcinoma using Sonazoid(R)-enhanced ultrasound, gadolinium diethylene-triaminepentaacetic acid-enhanced magnetic resonance imaging, and contrast-enhanced computed tomography. Oncology 2011;81Suppl 1:66-72 https://doi.org/10.1159/000333264
  30. Goto E, Masuzaki R, Tateishi R, Kondo Y, Imamura J, Goto T, et al. Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma. J Gastroenterol 2012;47:477-485 https://doi.org/10.1007/s00535-011-0512-9
  31. Hatanaka K, Kudo M, Minami Y, Maekawa K. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology 2008;75 Suppl 1:42-47 https://doi.org/10.1159/000173423
  32. Hatanaka K, Kudo M, Minami Y, Ueda T, Tatsumi C, Kitai S, et al. Differential diagnosis of hepatic tumors: value of contrast-enhanced harmonic sonography using the newly developed contrast agent, Sonazoid. Intervirology 2008;51Suppl 1:61-69 https://doi.org/10.1159/000122600
  33. Hsiao CY, Chen PD, Huang KW. A prospective assessment of the diagnostic value of contrast-enhanced ultrasound, dynamic computed tomography and magnetic resonance imaging for patients with small liver tumors. J Clin Med 2019;8:1353
  34. Kan M, Hiraoka A, Uehara T, Hidaka S, Ichiryu M, Nakahara H, et al. Evaluation of contrast-enhanced ultrasonography using perfluorobutane (Sonazoid(R)) in patients with small hepatocellular carcinoma: comparison with dynamic computed tomography. Oncol Lett 2010;1:485-488 https://doi.org/10.3892/ol_00000085
  35. Kawada N, Ohkawa K, Tanaka S, Matsunaga T, Uehara H, Ioka T, et al. Improved diagnosis of well-differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid-enhanced magnetic resonance imaging and Sonazoid contrast-enhanced ultrasonography. Hepatol Res 2010;40:930-936 https://doi.org/10.1111/j.1872-034X.2010.00697.x
  36. Luo W, Numata K, Morimoto M, Kondo M, Takebayashi S, Okada M, et al. Focal liver tumors: characterization with 3D perflubutane microbubble contrast agent-enhanced US versus 3D contrast-enhanced multidetector CT. Radiology 2009;251:287-295 https://doi.org/10.1148/radiol.2511081324
  37. Luo W, Numata K, Morimoto M, Nozaki A, Ueda M, Kondo M, et al. Differentiation of focal liver lesions using three-dimensional ultrasonography: retrospective and prospective studies. World J Gastroenterol 2010;16:2109-2119 https://doi.org/10.3748/wjg.v16.i17.2109
  38. Lv K, Zhai H, Jiang Y, Liang P, Xu HX, Du L, et al. Prospective assessment of diagnostic efficacy and safety of Sonazoid(TM) and SonoVue((R)) ultrasound contrast agents in patients with focal liver lesions. Abdom Radiol (NY) 2021;46:4647-4659 https://doi.org/10.1007/s00261-021-03010-1
  39. Masuzaki R, Shiina S, Tateishi R, Yoshida H, Goto E, Sugioka Y, et al. Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma. J Gastroenterol Hepatol 2011;26:759-764 https://doi.org/10.1111/j.1440-1746.2010.06559.x
  40. Mita K, Kim SR, Kudo M, Imoto S, Nakajima T, Ando K, et al. Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm. World J Gastroenterol 2010;16:4187-4192 https://doi.org/10.3748/wjg.v16.i33.4187
  41. Moriyasu F, Itoh K. Efficacy of perflubutane microbubble-enhanced ultrasound in the characterization and detection of focal liver lesions: phase 3 multicenter clinical trial. AJR Am J Roentgenol 2009;193:86-95 https://doi.org/10.2214/AJR.08.1618
  42. Sugimoto K, Kim SR, Imoto S, Tohyama M, Kim SK, Matsuoka T, et al. Characteristics of hypovascular versus hypervascular well-differentiated hepatocellular carcinoma smaller than 2 cm - focus on tumor size, markers and imaging detectability. Dig Dis 2015;33:721-727 https://doi.org/10.1159/000439078
  43. Sugimoto K, Moriyasu F, Takeuchi H, Kojima M, Ogawa S, Sano T, et al. Optimal injection rate of ultrasound contrast agent for evaluation of focal liver lesions using an automatic power injector: a pilot study. Springerplus 2016;5:749
  44. Zhai HY, Liang P, Yu J, Cao F, Kuang M, Liu FY, et al. Comparison of Sonazoid and SonoVue in the diagnosis of focal liver lesions: a preliminary study. J Ultrasound Med 2019;38:2417-2425 https://doi.org/10.1002/jum.14940
  45. Wilson SR, Lyshchik A, Piscaglia F, Cosgrove D, Jang HJ, Sirlin C, et al. CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI. Abdom Radiol (NY) 2018;43:127-142 https://doi.org/10.1007/s00261-017-1250-0
  46. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017;11:317-370 https://doi.org/10.1007/s12072-017-9799-9
  47. Korean Liver Cancer Association (KLCA), National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022;28:583-705 https://doi.org/10.3350/cmh.2022.0294
  48. Mandai M, Koda M, Matono T, Nagahara T, Sugihara T, Ueki M, et al. Assessment of hepatocellular carcinoma by contrast-enhanced ultrasound with perfluorobutane microbubbles: comparison with dynamic CT. Br J Radiol 2011;84:499-507 https://doi.org/10.1259/bjr/38682601
  49. Wang F, Numata K, Chuma M, Miwa H, Moriya S, Ogushi K, et al. A study on the inconsistency of arterial phase hypervascularity detection between contrast-enhanced ultrasound using Sonazoid and gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid magnetic resonance imaging of hepatocellular carcinoma lesions. J Med Ultrason (2001) 2021;48:215-224 https://doi.org/10.1007/s10396-021-01086-2
  50. Chou YH, Liang JD, Wang SY, Hsu SJ, Hu JT, Yang SS, et al. Safety of perfluorobutane (Sonazoid) in characterizing focal liver lesions. J Med Ultrasound 2019;27:81-85 https://doi.org/10.4103/JMU.JMU_44_19
  51. Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014;60:1268-1289 https://doi.org/10.1016/j.jhep.2014.01.021
  52. Chung YE, Kim MJ, Park YN, Choi JY, Pyo JY, Kim YC, et al. Varying appearances of cholangiocarcinoma: radiologic-pathologic correlation. Radiographics 2009;29:683-700 https://doi.org/10.1148/rg.293085729
  53. Chen LD, Xu HX, Xie XY, Xie XH, Xu ZF, Liu GJ, et al. Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol 2010;20:743-753 https://doi.org/10.1007/s00330-009-1599-8
  54. Li R, Yuan MX, Ma KS, Li XW, Tang CL, Zhang XH, et al. Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis. PLoS One 2014;9:e98612
  55. Dietrich CF, Cui XW, Boozari B, Hocke M, Ignee A. Contrast-enhanced ultrasound (CEUS) in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma, comments on the AASLD guidelines. Ultraschall Med 2012;33 Suppl 1:S57-S66 https://doi.org/10.1055/s-0032-1312903
  56. Jo PC, Jang HJ, Burns PN, Burak KW, Kim TK, Wilson SR. Integration of contrast-enhanced US into a multimodality approach to imaging of nodules in a cirrhotic liver: how I do it. Radiology 2017;282:317-331 https://doi.org/10.1148/radiol.2016151732
  57. Burns PN, Wilson SR. Focal liver masses: enhancement patterns on contrast-enhanced images--concordance of US scans with CT scans and MR images. Radiology 2007;242:162-174 https://doi.org/10.1148/radiol.2421051006
  58. Rimola J, Forner A, Reig M, Vilana R, de Lope CR, Ayuso C, et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology 2009;50:791-798 https://doi.org/10.1002/hep.23071
  59. D'Onofrio M, Vecchiato F, Cantisani V, Barbi E, Passamonti M, Ricci P, et al. Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging. Radiol Med 2008;113:76-86 https://doi.org/10.1007/s11547-008-0225-1
  60. Patel S, Saito A, Yoneda Y, Hayano T, Shiratori K. Comparing enhancement and washout patterns of hepatic lesions between sonazoid-enhanced ultrasound and contrast-enhanced computed tomography. J Med Ultrason (2001) 2010;37:167-173 https://doi.org/10.1007/s10396-010-0277-4
  61. Feng Y, Qin XC, Luo Y, Li YZ, Zhou X. Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation. Ultrasound Med Biol 2015;41:1553-1560 https://doi.org/10.1016/j.ultrasmedbio.2015.01.026
  62. Zhu W, Qing X, Yan F, Luo Y, Li Y, Zhou X. Can the contrast-enhanced ultrasound washout rate be used to predict microvascular invasion in hepatocellular carcinoma? Ultrasound Med Biol 2017;43:1571-1580 https://doi.org/10.1016/j.ultrasmedbio.2017.04.003
  63. Leoni S, Serio I, Pecorelli A, Marinelli S, Bolondi L. Contrast-enhanced ultrasound in liver cancer. Hepat Oncol 2015;2:51-62 https://doi.org/10.2217/hep.14.25
  64. Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, et al. The AFSUMB consensus statements and recommendations for the clinical practice of contrast-enhanced ultrasound using Sonazoid. J Med Ultrasound 2020;28:59-82 https://doi.org/10.4103/JMU.JMU_124_19
  65. Luo W, Numata K, Kondo M, Morimoto M, Sugimori K, Hirasawa K, et al. Sonazoid-enhanced ultrasonography for evaluation of the enhancement patterns of focal liver tumors in the late phase by intermittent imaging with a high mechanical index. J Ultrasound Med 2009;28:439-448 https://doi.org/10.7863/jum.2009.28.4.439
  66. Son JH, Choi SH, Kim SY, Jang HY, Byun JH, Won HJ, et al. Validation of US liver imaging reporting and data system version 2017 in patients at high risk for hepatocellular carcinoma. Radiology 2019;292:390-397 https://doi.org/10.1148/radiol.2019190035
  67. Kudo M, Hatanaka K, Kumada T, Toyoda H, Tada T. Double-contrast ultrasound: a novel surveillance tool for hepatocellular carcinoma. Am J Gastroenterol 2011;106:368-370 https://doi.org/10.1038/ajg.2010.432
  68. Kudo M, Hatanaka K, Maekawa K. Newly developed novel ultrasound technique, defect reperfusion ultrasound imaging, using Sonazoid in the management of hepatocellular carcinoma. Oncology 2010;78 Suppl 1:40-45 https://doi.org/10.1159/000315229
  69. Kudo M, Ueshima K, Osaki Y, Hirooka M, Imai Y, Aso K, et al. B-mode ultrasonography versus contrast-enhanced ultrasonography for surveillance of hepatocellular carcinoma: a prospective multicenter randomized controlled trial. Liver Cancer 2019;8:271-280 https://doi.org/10.1159/000501082
  70. Park JH, Park MS, Lee SJ, Jeong WK, Lee JY, Park MJ, et al. Contrast-enhanced US with perfluorobutane for hepatocellular carcinoma surveillance: a multicenter diagnostic trial (SCAN). Radiology 2019;292:638-646 https://doi.org/10.1148/radiol.2019190183
  71. Tanaka H, Iijima H, Nouso K, Aoki N, Iwai T, Takashima T, et al. Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Hepatol Res 2012;42:376-384 https://doi.org/10.1111/j.1872-034X.2011.00936.x
  72. Kim JE, Kim SH, Lee SJ, Rhim H. Hypervascular hepatocellular carcinoma 1 cm or smaller in patients with chronic liver disease: characterization with gadoxetic acid-enhanced MRI that includes diffusion-weighted imaging. AJR Am J Roentgenol 2011;196:W758-W765 https://doi.org/10.2214/AJR.10.4394
  73. Park MJ, Kim YK, Lee MW, Lee WJ, Kim YS, Kim SH, et al. Small hepatocellular carcinomas: improved sensitivity by combining gadoxetic acid-enhanced and diffusion-weighted MR imaging patterns. Radiology 2012;264:761-770 https://doi.org/10.1148/radiol.12112517
  74. Lee MW, Kim YJ, Park HS, Yu NC, Jung SI, Ko SY, et al. Targeted sonography for small hepatocellular carcinoma discovered by CT or MRI: factors affecting sonographic detection. AJR Am J Roentgenol 2010;194:W396-W400 https://doi.org/10.2214/AJR.09.3171
  75. Dohmen T, Kataoka E, Yamada I, Miura K, Ohshima S, Shibuya T, et al. Efficacy of contrast-enhanced ultrasonography in radiofrequency ablation for hepatocellular carcinoma. Intern Med 2012;51:1-7 https://doi.org/10.2169/internalmedicine.51.6042
  76. Lee SJ, Won HJ, Kim KW, Shin YM, Kim PN. Value of contrast-enhanced sonography of small hepatocellular carcinoma with Sonazoid prior to radiofrequency ablation. J Clin Ultrasound 2017;45:383-390 https://doi.org/10.1002/jcu.22469
  77. Minami Y, Kudo M, Hatanaka K, Kitai S, Inoue T, Hagiwara S, et al. Radiofrequency ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles (Sonazoid) for hepatic malignancies: an initial experience. Liver Int 2010;30:759-764 https://doi.org/10.1111/j.1478-3231.2010.02226.x
  78. Min JH, Lim HK, Lim S, Kang TW, Song KD, Choi SY, et al. Radiofrequency ablation of very-early-stage hepatocellular carcinoma inconspicuous on fusion imaging with B-mode US: value of fusion imaging with contrast-enhanced US. Clin Mol Hepatol 2014;20:61-70 https://doi.org/10.3350/cmh.2014.20.1.61
  79. Lee MW, Lim HK, Rhim H, Cha DI, Kang TW, Song KD, et al. Percutaneous radiofrequency ablation of small (1-2 cm) hepatocellular carcinomas inconspicuous on B-mode ultrasonographic imaging: usefulness of combined fusion imaging with MRI and contrast-enhanced ultrasonography. Can J Gastroenterol Hepatol 2018;2018:7926923
  80. Inoue T, Kudo M, Hatanaka K, Arizumi T, Takita M, Kitai S, et al. Usefulness of contrast-enhanced ultrasonography to evaluate the post-treatment responses of radiofrequency ablation for hepatocellular carcinoma: comparison with dynamic CT. Oncology 2013;84 Suppl 1:51-57 https://doi.org/10.1159/000345890
  81. Nishigaki Y, Hayashi H, Tomita E, Suzuki Y, Watanabe N, Watanabe S, et al. Usefulness of contrast-enhanced ultrasonography using Sonazoid for the assessment of therapeutic response to percutaneous radiofrequency ablation for hepatocellular carcinoma. Hepatol Res 2015;45:432-440 https://doi.org/10.1111/hepr.12370
  82. Takahashi M, Maruyama H, Shimada T, Kamezaki H, Okabe S, Kanai F, et al. Linear enhancement after radio-frequency ablation for hepatocellular carcinoma: is it a sign of recurrence? Ultrasound Med Biol 2012;38:1902-1910 https://doi.org/10.1016/j.ultrasmedbio.2012.07.003
  83. Shiozawa K, Watanabe M, Takayama R, Takahashi M, Wakui N, Iida K, et al. Evaluation of local recurrence after treatment for hepatocellular carcinoma by contrast-enhanced ultrasonography using Sonazoid: comparison with dynamic computed tomography. J Clin Ultrasound 2010;38:182-189 https://doi.org/10.1002/jcu.20685
  84. Shiozawa K, Matsui T, Murakami T, Watanabe M, Maetani I. Predicting therapeutic efficacy of transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma using contrast-enhanced ultrasound. Diagnostics (Basel) 2021;11:291
  85. Takizawa K, Numata K, Morimoto M, Kondo M, Nozaki A, Moriya S, et al. Use of contrast-enhanced ultrasonography with a perflubutane-based contrast agent performed one day after transarterial chemoembolization for the early assessment of residual viable hepatocellular carcinoma. Eur J Radiol 2013;82:1471-1480 https://doi.org/10.1016/j.ejrad.2013.04.045
  86. Xia Y, Kudo M, Minami Y, Hatanaka K, Ueshima K, Chung H, et al. Response evaluation of transcatheter arterial chemoembolization in hepatocellular carcinomas: the usefulness of Sonazoid-enhanced harmonic sonography. Oncology 2008;75 Suppl 1:99-105 https://doi.org/10.1159/000173430
  87. Funaoka A, Numata K, Takeda A, Saigusa Y, Tsurugai Y, Nihonmatsu H, et al. Use of contrast-enhanced ultrasound with Sonazoid for evaluating the radiotherapy efficacy for hepatocellular carcinoma. Diagnostics (Basel) 2021;11:486
  88. Kamachi N, Nakano M, Okamura S, Niizeki T, Iwamoto H, Shimose S, et al. Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast-enhanced ultrasound. Cancer Rep (Hoboken) 2022;5:e1471
  89. Shiozawa K, Watanabe M, Ikehara T, Shimizu R, Shinohara M, Igarashi Y, et al. Evaluation of sorafenib for advanced hepatocellular carcinoma with low α-fetoprotein in arrival time parametric imaging using contrast-enhanced ultrasonography. J Med Ultrason (2001) 2017;44:101-107 https://doi.org/10.1007/s10396-016-0757-2
  90. Shiozawa K, Watanabe M, Ikehara T, Kogame M, Kikuchi Y, Igarashi Y, et al. Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: preliminary result. Oncol Lett 2016;12:579-584 https://doi.org/10.3892/ol.2016.4669
  91. Sugimoto K, Moriyasu F, Saito K, Rognin N, Kamiyama N, Furuichi Y, et al. Hepatocellular carcinoma treated with sorafenib: early detection of treatment response and major adverse events by contrast-enhanced US. Liver Int 2013;33:605-615 https://doi.org/10.1111/liv.12098