Journal of Gastroenterology

, Volume 51, Issue 5, pp 421–433 | Cite as

Role of contrast-enhanced ultrasonography with Sonazoid for hepatocellular carcinoma: evidence from a 10-year experience

  • Hitoshi MaruyamaEmail author
  • Tadashi Sekimoto
  • Osamu Yokosuka


Hepatocellular carcinoma (HCC) represents primary liver cancer. Because the development of HCC limits the prognosis as well as the quality of life of the patients, its management should be properly conducted based on an accurate diagnosis. The liver is the major target organ of ultrasound (US), which is the simple, non-invasive, and real-time imaging method available worldwide. Microbubble-based contrast agents are safe and reliable and have become popular, which has resulted in the improvement of diagnostic performances of US due to the increased detectability of the peripheral blood flow. Sonazoid (GE Healthcare, Waukesha, WI, USA), a second-generation contrast agent, shows the unique property of accumulation in the liver and spleen. Contrast-enhanced US with Sonazoid is now one of the most frequently used modalities in the practical management of liver tumors, including the detection and characterization of the nodule, evaluation of the effects of non-surgical treatment, intraoperative support, and post-treatment surveillance. This article reviews the 10-year evidence for contrast-enhanced US with Sonazoid in the practical management of HCC.


Hepatocellular carcinoma Contrast-enhanced ultrasound Sonazoid 



Area under the receiver operating characteristic curve


Contrast-enhanced ultrasound


Computed tomography


CT arteriography


CT arterioportal angiography


Dysplastic nodule


Gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid-MRI


Hepatocellular carcinoma


Intrahepatic cholangiocellular carcinoma


Moderately differentiated hepatocellular carcinoma


Maximum intensity projection


New focal liver lesions


Not statistically significant


Partial response


Progressive disease


Poorly differentiated hepatocellular carcinoma


Regenerative nodule


Radiofrequency ablation


Stable disease


Contrast-enhanced ultrasound with Sonazoid


Superparamagnetic iron oxide magnetic resonance imaging


Transcatheter arterial chemoembolization




Well-differentiated hepatocellular carcinoma


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Kudo M, Matsui O, Izumi N, Liver Cancer Study Group of Japan, et al. Surveillance and diagnostic algorithm for hepatocellular carcinoma proposed by the Liver Cancer Study Group of Japan: 2014 update. Oncology. 2014;87(Suppl 1):7–21.CrossRefPubMedGoogle Scholar
  2. 2.
    Jang HJ, Kim TK, Burns PN, et al. CEUS: an essential component in a multimodality approach to small nodules in patients at high-risk for hepatocellular carcinoma. Eur J Radiol. 2015;84:1623–35.CrossRefPubMedGoogle Scholar
  3. 3.
    Bouakaz A, de Jong N. WFUMB Safety Symposium on Echo-Contrast Agents: nature and types of ultrasound contrast agents. Ultrasound Med Biol. 2007;33:187–96.CrossRefPubMedGoogle Scholar
  4. 4.
    Numata K, Luo W, Morimoto M, et al. Contrast-enhanced ultrasound of hepatocellular carcinoma. World J Radiol. 2010;2:68–82.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Claudon M, Dietrich CF, Choi BI, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver—update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 2013;39:187–210.CrossRefPubMedGoogle Scholar
  6. 6.
    Sontum PC. Physicochemical characteristics of SonazoidTM, a new contrast agent for ultrasound imaging. Ultrasound Med Biol. 2008;34:824–33.CrossRefPubMedGoogle Scholar
  7. 7.
    Sasaki S, Iijima H, Moriyasu F, Hidehiko W. Definition of contrast enhancement phases of the liver using a perfluoro-based microbubble agent, perflubutane microbubbles. Ultrasound Med Biol. 2009;35:1819–27.CrossRefGoogle Scholar
  8. 8.
    Drugs in Japan forum. Drugs in Japan, ethical drugs 2011. Tokyo: Jiho; 2010.Google Scholar
  9. 9.
    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.CrossRefPubMedGoogle Scholar
  10. 10.
    Shimada T, Maruyama H, Sekimoto T, et al. Heterogeneous staining in the liver parenchyma after the injection of perflubutane microbubble contrast agent. Ultrasound Med Biol. 2012;38:1317–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Inoue T, Kudo M, Hatanaka K, et al. Imaging of hepatocellular carcinoma: qualitative and quantitative analysis of post vascular phase contrast-enhanced ultrasonography with Sonazoid. Comparison with super paramagnetic iron oxide magnetic resonance images. Oncology. 2008;75(Suppl 1):48–54.CrossRefPubMedGoogle Scholar
  12. 12.
    Goto E, Masuzaki R, Tateishi R, et al. Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma. J Gastroenterol. 2012;47:477–85.CrossRefPubMedGoogle Scholar
  13. 13.
    Hatanaka K, Chung H, Kudo M, et al. Usefulness of the post-vascular phase of contrast-enhanced ultrasonography with Sonazoid in the evaluation of gross types of hepatocellular carcinoma. Oncology. 2010;78(Suppl 1):53–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Tada T, Kumada T, Toyoda H, et al. Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinomas. Eur Radiol. 2014;24:2157–66.CrossRefPubMedGoogle Scholar
  15. 15.
    Hatanaka K, Minami Y, Kudo M, et al. The gross classification of hepatocellular carcinoma: usefulness of contrast-enhanced US. J Clin Ultrasound. 2014;42:1–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Mandai M, Koda M, Matono T, et al. Assessment of hepatocellular carcinoma by contrast-enhanced ultrasound with perfluorobutane microbubbles: comparison with dynamic CT. Br J Radiol. 2011;84:499–507.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Numata K, Fukuda H, Miwa H, et al. Contrast-enhanced ultrasonography findings using a perflubutane-based contrast agent in patients with early hepatocellular carcinoma. Eur J Radiol. 2014;83:95–102.CrossRefPubMedGoogle Scholar
  18. 18.
    Maruyama H, Takahashi M, Ishibashi H, et al. Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases. Br J Radiol. 2012;85:351–7.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kudo M, Hatanaka K, Inoue T, et al. 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):60–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Kita R, Sakamoto A, Nagata Y, et al. Visualization of blood drainage area from hypervascular hepatocellular carcinoma on ultrasonographic images during hepatic arteriogram: comparison with depiction of drainage area on contrast-enhanced ultrasound. Hepatol Res. 2012;42:999–1007.CrossRefPubMedGoogle Scholar
  21. 21.
    Sugimoto K, Shiraishi J, Moriyasu F, et al. Computer-aided diagnosis of focal liver lesions by use of physicians’ subjective classification of echogenic patterns in baseline and contrast-enhanced ultrasonography. Acad Radiol. 2009;16:401–11.CrossRefPubMedGoogle Scholar
  22. 22.
    Numata K, Fukuda H, Nihonmatsu H, et al. Use of vessel patterns on contrast-enhanced ultrasonography using a perflubutane-based contrast agent for the differential diagnosis of regenerative nodules from early hepatocellular carcinoma or high-grade dysplastic nodules in patients with chronic liver disease. Abdom Imaging. 2015;40:2372–83.CrossRefPubMedGoogle Scholar
  23. 23.
    Luo W, Numata K, Kondo M, 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;28:439–48.PubMedGoogle Scholar
  24. 24.
    Hatanaka K, Kudo M, Minami Y, et al. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology. 2008;75(Suppl 1):42–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Kan M, Hiraoka A, Uehara T, et al. Evaluation of contrast-enhanced ultrasonography using perfluorobutane (Sonazoid®) in patients with small hepatocellular carcinoma: comparison with dynamic computed tomography. Oncol Lett. 2010;1:485–8.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Takahashi M, Maruyama H, Shimada T, et al. Characterization of hepatic lesions (≤30 mm) with liver-specific contrast agents: a comparison between ultrasound and magnetic resonance imaging. Eur J Radiol. 2013;82:75–84.CrossRefPubMedGoogle Scholar
  27. 27.
    Mita K, Kim SR, Kudo M, et al. Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm. World J Gastroenterol. 2010;16:4187–92.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kawada N, Ohkawa K, Tanaka S, 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;40:930–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Alaboudy A, Inoue T, Hatanaka K, et al. Usefulness of combination of imaging modalities in the diagnosis of hepatocellular carcinoma using Sonazoid®-enhanced ultrasound, gadolinium diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging, and contrast-enhanced computed tomography. Oncology. 2011;81(Suppl 1):66–72.CrossRefPubMedGoogle Scholar
  30. 30.
    Ohama H, Imai Y, Nakashima O, et al. Images of Sonazoid-enhanced ultrasonography in multistep hepatocarcinogenesis: comparison with Gd-EOB-DTPA-enhanced MRI. J Gastroenterol. 2014;49:1081–93.CrossRefPubMedGoogle Scholar
  31. 31.
    Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol. 2009;44(Suppl 19):112–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Suzuki K, Okuda Y, Ota M, et al. Diagnosis of hepatocellular carcinoma nodules in patients with chronic liver disease using contrast-enhanced sonography: usefulness of the combination of arterial- and Kupffer-phase enhancement patterns. J Ultrasound Med. 2015;34:423–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Tanaka H, Iijima H, Higashiura A, et al. New malignant grading system for hepatocellular carcinoma using the Sonazoid contrast agent for ultrasonography. J Gastroenterol. 2014;49:755–63.CrossRefPubMedGoogle Scholar
  34. 34.
    Kondo T, Maruyama H, Kiyono S, et al. Intensity-based assessment of microbubble-enhanced ultrasonography: phase-related diagnostic ability for cellular differentiation of hepatocellular carcinoma. Ultrasound Med Biol. 2015;41:3079–87.CrossRefPubMedGoogle Scholar
  35. 35.
    Maruyama H, Takahashi M, Ishibashi H, et al. Changes in tumor vascularity precede microbubble contrast accumulation deficit in the process of dedifferentiation of hepatocellular carcinoma. Eur J Radiol. 2010;75:e102–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Takahashi M, Maruyama H, Ishibashi H, et al. Contrast-enhanced ultrasound with perflubutane microbubble agent: evaluation of differentiation of hepatocellular carcinoma. AJR Am J Roentgenol. 2011;196:W123–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Sugimoto K, Moriyasu F, Saito K, et al. Comparison of Kupffer-phase Sonazoid-enhanced sonography and hepatobiliary-phase gadoxetic acid-enhanced magnetic resonance imaging of hepatocellular carcinoma and correlation with histologic grading. J Ultrasound Med. 2012;31:529–38.PubMedGoogle Scholar
  38. 38.
    Kondo T, Maruyama H, Sekimoto T, et al. Natural history of postvascular-phase iso-enhanced lesions on the sonogram in chronic liver diseases. J Gastroenterol Hepatol. 2014;29:165–72.CrossRefPubMedGoogle Scholar
  39. 39.
    Korenaga K, Korenaga M, Furukawa M, et al. Usefulness of Sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and super paramagnetic iron oxide magnetic resonance images. J Gastroenterol. 2009;44:733–41.CrossRefPubMedGoogle Scholar
  40. 40.
    Maruyama H, Takahashi M, Sekimoto T, et al. Heterogeneity of microbubble accumulation: a novel approach to discriminate between well-differentiated hepatocellular carcinomas and regenerative nodules. Ultrasound Med Biol. 2012;38:383–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Choi BI, Lee JM, Kim TK, et al. Diagnosing borderline hepatic nodules in hepatocarcinogenesis: imaging performance. AJR Am J Roentgenol. 2015;205:10–21.CrossRefPubMedGoogle Scholar
  42. 42.
    Kudo M, Hatanaka K, Kumada T, et al. Double-contrast ultrasound: a novel surveillance tool for hepatocellular carcinoma. Am J Gastroenterol. 2011;106:368–70.CrossRefPubMedGoogle Scholar
  43. 43.
    Maruyama H, Takahashi M, Ishibashi H, et al. Ultrasound-guided treatments under low acoustic power contrast harmonic imaging for hepatocellular carcinomas undetected by B-mode ultrasonography. Liver Int. 2009;29:708–14.CrossRefPubMedGoogle Scholar
  44. 44.
    Miyamoto N, Hiramatsu K, Tsuchiya K, et al. Contrast-enhanced sonography-guided radiofrequency ablation for the local recurrence of previously treated hepatocellular carcinoma undetected by B-mode sonography. J Clin Ultrasound. 2010;38:339–45.PubMedGoogle Scholar
  45. 45.
    Numata K, Morimoto M, Ogura T, et al. Ablation therapy guided by contrast-enhanced sonography with Sonazoid for hepatocellular carcinoma lesions not detected by conventional sonography. J Ultrasound Med. 2008;27:395–406.PubMedGoogle Scholar
  46. 46.
    Minami Y, Kudo M, Hatanaka K, et al. Radiofrequency ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles (Sonazoid) for hepatic malignancies: an initial experience. Liver Int. 2010;30:759–64.CrossRefPubMedGoogle Scholar
  47. 47.
    Kudo M. New sonographic techniques for the diagnosis and treatment of hepatocellular carcinoma. Hepatol Res. 2007;37(Suppl 2):S193–9.CrossRefPubMedGoogle Scholar
  48. 48.
    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):40–5.CrossRefPubMedGoogle Scholar
  49. 49.
    Ikeda K, Osaki Y, Nakanishi H, et al. Recent progress in radiofrequency ablation therapy for hepatocellular carcinoma. Oncology. 2014;87(Suppl 1):73–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Meloni MF, Smolock A, Cantisani V, et al. Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors. Eur J Radiol. 2015;84:1666–74.CrossRefPubMedGoogle Scholar
  51. 51.
    Hiraoka A, Ichiryu M, Tazuya N, et al. Clinical translation in the treatment of hepatocellular carcinoma following the introduction of contrast-enhanced ultrasonography with Sonazoid. Oncol Lett. 2010;1:57–61.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Masuzaki R, Shiina S, Tateishi R, et al. Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma. J Gastroenterol Hepatol. 2011;26:759–64.CrossRefPubMedGoogle Scholar
  53. 53.
    Dohmen T, Kataoka E, Yamada I, et al. Efficacy of contrast-enhanced ultrasonography in radiofrequency ablation for hepatocellular carcinoma. Intern Med. 2012;51:1–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Kudo M. Diagnostic imaging of hepatocellular carcinoma: recent progress. Oncology. 2011;81(Suppl 1):73–85.CrossRefPubMedGoogle Scholar
  55. 55.
    Inoue T, Kudo M, Hatanaka K, 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):51–7.CrossRefPubMedGoogle Scholar
  56. 56.
    Nishigaki Y, Hayashi H, Tomita E, 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;45:432–40.CrossRefPubMedGoogle Scholar
  57. 57.
    Inoue T, Minami Y, Chung H, et al. Radiofrequency ablation for hepatocellular carcinoma: assistant techniques for difficult cases. Oncology. 2010;78(Suppl 1):94–101.CrossRefPubMedGoogle Scholar
  58. 58.
    Andreana L, Kudo M, Hatanaka K, et al. Contrast-enhanced ultrasound techniques for guiding and assessing response to locoregional treatments for hepatocellular carcinoma. Oncology. 2010;78(Suppl 1):68–77.CrossRefPubMedGoogle Scholar
  59. 59.
    Takahashi M, Maruyama H, Shimada T, et al. Linear enhancement after radio-frequency ablation for hepatocellular carcinoma: Is it a sign of recurrence? Ultrasound Med Biol. 2012;38:1902–10.CrossRefPubMedGoogle Scholar
  60. 60.
    Maruyama H, Takahashi M, Shimada T, et al. Pretreatment microbubble-induced enhancement in hepatocellular carcinoma predicts intrahepatic distant recurrence after radiofrequency ablation. AJR Am J Roentgenol. 2013;200:570–7.CrossRefPubMedGoogle Scholar
  61. 61.
    Xia Y, Kudo M, Minami Y, 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.CrossRefPubMedGoogle Scholar
  62. 62.
    Takizawa K, Numata K, Morimoto M, et al. Use of contrast-enhanced ultrasonography with a perflubutane-based contrast agent performed 1 day after transarterial chemoembolization for the early assessment of residual viable hepatocellular carcinoma. Eur J Radiol. 2013;82:1471–80.CrossRefPubMedGoogle Scholar
  63. 63.
    Kudo M. The 2008 Okuda lecture: management of hepatocellular carcinoma: from surveillance to molecular targeted therapy. J Gastroenterol Hepatol. 2010;25:439–52.CrossRefPubMedGoogle Scholar
  64. 64.
    Shiozawa K, Watanabe M, Kikuchi Y, et al. Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced ultrasonography: a pilot study. World J Gastroenterol. 2012;18:5753–8.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Sugimoto K, Moriyasu F, Saito K, et al. Hepatocellular carcinoma treated with sorafenib: early detection of treatment response and major adverse events by contrast-enhanced US. Liver Int. 2013;33:605–15.CrossRefPubMedGoogle Scholar
  66. 66.
    Abo T, Nanashima A, Tobinaga S, et al. Usefulness of intraoperative diagnosis of hepatic tumors located at the liver surface and hepatic segmental visualization using indocyanine green-photodynamic eye imaging. Eur J Surg Oncol. 2015;41:257–64.CrossRefPubMedGoogle Scholar
  67. 67.
    Uchiyama K, Ueno M, Ozawa S, et al. Combined intraoperative use of contrast-enhanced ultrasonography imaging using a Sonazoid and fluorescence navigation system with indocyanine green during anatomical hepatectomy. Langenbecks Arch Surg. 2011;396:1101–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Nanashima A, Tobinaga S, Abo T, et al. Usefulness of Sonazoid-ultrasonography during hepatectomy in patients with liver tumors: a preliminary study. J Surg Oncol. 2011;103:152–7.CrossRefPubMedGoogle Scholar
  69. 69.
    Arita J, Takahashi M, Hata S, et al. Usefulness of contrast-enhanced intraoperative ultrasound using Sonazoid in patients with hepatocellular carcinoma. Ann Surg. 2011;254:992–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Mitsunori Y, Tanaka S, Nakamura N, et al. Contrast-enhanced intraoperative ultrasound for hepatocellular carcinoma: high sensitivity of diagnosis and therapeutic impact. J Hepatobiliary Pancreat Sci. 2013;20:234–42.CrossRefPubMedGoogle Scholar
  71. 71.
    Arita J, Hasegawa K, Takahashi M, et al. Correlation between contrast-enhanced intraoperative ultrasound using Sonazoid and histologic grade of resected hepatocellular carcinoma. AJR Am J Roentgenol. 2011;196:1314–21.CrossRefPubMedGoogle Scholar
  72. 72.
    Sato K, Tanaka S, Mitsunori Y, et al. Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: clinical and biological significance. Hepatology. 2013;57:1436–47.CrossRefPubMedGoogle Scholar
  73. 73.
    Luo W, Numata K, Morimoto M, et al. Three-dimensional contrast-enhanced sonography of vascular patterns of focal liver tumors: pilot study of visualization methods. AJR Am J Roentgenol. 2009;192:165–73.CrossRefPubMedGoogle Scholar
  74. 74.
    Luo W, Numata K, Morimoto M, et al. Clinical utility of contrast-enhanced three-dimensional ultrasound imaging with Sonazoid: findings on hepatocellular carcinoma lesions. Eur J Radiol. 2009;72:425–31.CrossRefPubMedGoogle Scholar
  75. 75.
    Numata K, Fukuda H, Ohto M, et al. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent. Eur J Radiol. 2010;75:e67–75.CrossRefPubMedGoogle Scholar
  76. 76.
    Kunishi Y, Numata K, Morimoto M, et al. Efficacy of fusion imaging combining sonography and hepatobiliary phase MRI with Gd-EOB-DTPA to detect small hepatocellular carcinoma. AJR Am J Roentgenol. 2012;198:106–14.CrossRefPubMedGoogle Scholar
  77. 77.
    Makino Y, Imai Y, Ohama H, et al. Ultrasonography fusion imaging system increases the chance of radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on conventional ultrasonography. Oncology. 2013;84(Suppl 1):44–50.CrossRefPubMedGoogle Scholar
  78. 78.
    Min JH, Lim HK, Lim S, 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.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Numata K, Fukuda H, Morimoto M, et al. Use of fusion imaging combining contrast-enhanced ultrasonography with a perflubutane-based contrast agent and contrast-enhanced computed tomography for the evaluation of percutaneous radiofrequency ablation of hypervascular hepatocellular carcinoma. Eur J Radiol. 2012;81:2746–53.CrossRefPubMedGoogle Scholar
  80. 80.
    Shindoh J, Seyama Y, Umekita N. Three-dimensional staining of liver segments with an ultrasound contrast agent as an aid to anatomic liver resection. J Am Coll Surg. 2012;215:e5–10.CrossRefPubMedGoogle Scholar
  81. 81.
    Bota S, Piscaglia F, Marinelli S, et al. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver Cancer. 2012;1:190–200.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Tanaka H, Iijima H, Nouso K, et al. Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Hepatol Res. 2012;42:376–84.CrossRefPubMedGoogle Scholar
  83. 83.
    Shiozawa K, Watanabe M, Takayama R, 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;38:182–9.PubMedGoogle Scholar

Copyright information

© Japanese Society of Gastroenterology 2015

Authors and Affiliations

  • Hitoshi Maruyama
    • 1
    Email author
  • Tadashi Sekimoto
    • 1
  • Osamu Yokosuka
    • 1
  1. 1.Department of Gastroenterology and NephrologyChiba University Graduate School of MedicineChibaJapan

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