Abdominal Radiology

, Volume 43, Issue 11, pp 3166–3175 | Cite as

Contrast-enhanced ultrasonography in interventional oncology

  • Sriharsha Gummadi
  • John R. Eisenbrey
  • Andrej LyshchikEmail author
Pictorial essay


Contrast-enhanced ultrasound (CEUS) has evolved from the use of agitated saline to second generation bioengineered microbubbles designed to withstand insonation with limited destruction. While only one of these newer agents is approved by the Food and Drug Administration for use outside echocardiography, interventional radiologists are increasingly finding off-label uses for ultrasound contrast agents. Notably, these agents have an extremely benign safety profile with no hepatic or renal toxicities and no radiation exposure. Alongside diagnostic applications, CEUS has begun to develop its own niche within the realm of interventional oncology. Certainly, the characterization of focal solid organ lesions (such as hepatic and renal lesions) by CEUS has been an important development. However, interventional oncologists are finding that the dynamic and real-time information afforded by CEUS can improve biopsy guidance, ablation therapy, and provide early evidence of tumor viability after locoregional therapy. Even more novel uses of CEUS include lymph node mapping and sentinel lymph node localization. Critical areas of research still exist. The purpose of this article is to provide a narrative review of the emerging roles of CEUS in interventional oncology.


Contrast-enhanced ultrasound Interventional oncology Interventional radiology 


Compliance with ethical standards


Research reported in this publication was supported by the National Institutes of Health under the award numbers R01CA194307 and R01CA215520. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflicts of interest

The authors report non-financial and grant support from GE Healthcare and Toshiba Medical Systems outside the submitted work.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Because all clinical vignettes contain only de-identified retrospective data and are utilized for educational purposes only, no consent outside standard procedural consent was requested of any patients.


  1. 1.
    Paefgen V, Doleschel D, Kiessling F (2015) Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery. Front Pharmacol 6:197CrossRefGoogle Scholar
  2. 2.
    Piscaglia F, Nolsøe C, Dietrich CF, et al. (2012) The EFSUMB guidelines and recommendations on the clinical practice of contrast enhanced ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall in der Medizin-Eur J Ultrasound 33(01):33–59CrossRefGoogle Scholar
  3. 3.
    Claudon M, Dietrich CF, Choi BI, et al. (2013) Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver—update 2012. Ultraschall in der Medizin-Eur J Ultrasound 34(01):11–29Google Scholar
  4. 4.
    Eisenbrey JR, Sridharan A, Liu J-B, et al. (2015) Recent experiences and advances in contrast-enhanced subharmonic ultrasound. BioMed Res Int 2015:1–6CrossRefGoogle Scholar
  5. 5.
    Eisenbrey JR, Wilson CC, Ro RJ, et al. (2013) Correlation of ultrasound contrast agent derived blood flow parameters with immunohistochemical angiogenesis markers in murine xenograft tumor models. Ultrasonics 53(7):1384–1391CrossRefGoogle Scholar
  6. 6.
    Definity (R) [Package Insert] (2017) Lantheus Medical Imaging, North Billerica, MA, Accessed 6 Nov 2017
  7. 7.
    Muskula PR, Main ML (2017) Safety with echocardiographic contrast agents. Circulation 10(4):e005459PubMedGoogle Scholar
  8. 8.
    Lyshchik A, Kono Y, Dietrich CF, et al. (2017) Contrast-enhanced ultrasound of the liver: technical and lexicon recommendations from the ACR CEUS LI-RADS working group. Abdom Radiol 38:1–19Google Scholar
  9. 9.
    Barr RG (2013) Off-label use of ultrasound contrast agents for abdominal imaging in the United States. J Ultrasound Med 32(1):7–12CrossRefGoogle Scholar
  10. 10.
    Forsberg F, Piccoli CW, Liu J-B, et al. (2002) Hepatic tumor detection: MR imaging and conventional US versus pulse-inversion harmonic US of NC100100 during its reticuloendothelial system-specific phase. Radiology 222(3):824–829CrossRefGoogle Scholar
  11. 11.
    Li P, Hoppmann S, Du P, et al. (2017) Pharmacokinetics of Perfluorobutane after Intra-Venous Bolus Injection of Sonazoid in Healthy Chinese Volunteers. Ultrasound Med Biol 43(5):1031–1039CrossRefGoogle Scholar
  12. 12.
    Claudon M, Dietrich CF, Choi BI, et al. (2013) 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 39(2):187–210CrossRefGoogle Scholar
  13. 13.
    Wilson SR, Greenbaum LD, Goldberg BB (2009) Contrast-enhanced ultrasound: what is the evidence and what are the obstacles? Am J Roentgenol 193(1):55–60CrossRefGoogle Scholar
  14. 14.
    Wilson SR, Lyshchik A, Piscaglia F, et al. (2017) CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI. Abdom Radiol 43(1):1–16Google Scholar
  15. 15.
    Zarzour JG, Lockhart ME, West J, et al. (2017) Contrast-enhanced ultrasound classification of previously indeterminate renal lesions. J Ultrasound Med 36(9):1819–1827CrossRefGoogle Scholar
  16. 16.
    Barr RG, Peterson C, Hindi A (2013) Evaluation of indeterminate renal masses with contrast-enhanced US: a diagnostic performance study. Radiology 271(1):133–142CrossRefGoogle Scholar
  17. 17.
    Mauri G, Porazzi E, Cova L, et al. (2014) Intraprocedural contrast-enhanced ultrasound (CEUS) in liver percutaneous radiofrequency ablation: clinical impact and health technology assessment. Insights Imaging 5(2):209–216CrossRefGoogle Scholar
  18. 18.
    Zhao X, Wang W, Zhang S, et al. (2012) Improved outcome of percutaneous radiofrequency ablation in renal cell carcinoma: a retrospective study of intraoperative contrast-enhanced ultrasonography in 73 patients. Abdom Radiol 37(5):885–891CrossRefGoogle Scholar
  19. 19.
    Sever A, Jones S, Cox K, et al. (2009) Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer. Br J Surg 96(11):1295–1299CrossRefGoogle Scholar
  20. 20.
    Sparchez Z, Radu P, Zaharia T, et al. (2011) Usefulness of contrast enhanced ultrasound guidance in percutaneous biopsies of liver tumors. J Gastrointest Liver Dis 20(2):191–196Google Scholar
  21. 21.
    Wu W, Chen MH, Yan K, et al. (2006) Application of contrast-enhanced ultrasound to increase the diagnostic rate of liver tumor by biopsy. Zhonghua yi xue za zhi 86(2):116–120PubMedGoogle Scholar
  22. 22.
    Yoon SH, Lee KH, Kim SY, et al. (2010) Real-time contrast-enhanced ultrasound-guided biopsy of focal hepatic lesions not localised on B-mode ultrasound. Eur Radiol 20(8):2047–2056CrossRefGoogle Scholar
  23. 23.
    Cao B-S, Wu J-H, Li X-L, et al. (2011) Sonographically guided transthoracic biopsy of peripheral lung and mediastinal lesions. J Ultrasound Med 30(11):1479–1490CrossRefGoogle Scholar
  24. 24.
    Wang S, Yang W, Zhang H, et al. (2015) The role of contrast-enhanced ultrasound in selection indication and improveing diagnosis for transthoracic biopsy in peripheral pulmonary and mediastinal lesions. BioMed Res Int 2015:1–8Google Scholar
  25. 25.
    Mao F, Dong Y, Ji Z, et al. (2017) Comparison of contrast-enhanced ultrasound and conventional ultrasound for guiding peripheral pulmonary biopsies. Int J Clin Exp Med 10(2):3677Google Scholar
  26. 26.
    Sugimoto M, Takagi T, Hikichi T, et al. (2015) Conventional versus contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for diagnosis of solid pancreatic lesions: a prospective randomized trial. Pancreatology 15(5):538–541CrossRefGoogle Scholar
  27. 27.
    Boczko J, Messing E, Dogra V (2006) Transrectal sonography in prostate evaluation. Radiol Clin 44(5):679–687CrossRefGoogle Scholar
  28. 28.
    Halpern EJ, Gomella LG, Forsberg F, et al. (2012) Contrast enhanced transrectal ultrasound for the detection of prostate cancer: a randomized, double-blind trial of dutasteride pretreatment. J Urol 188(5):1739–1745CrossRefGoogle Scholar
  29. 29.
    Kundavaram CR, Halpern EJ, Trabulsi EJ (2012) Value of contrast-enhanced ultrasonography in prostate cancer. Curr Opin Urol 22(4):303–309CrossRefGoogle Scholar
  30. 30.
    Trabulsi EJ, Sackett D, Gomella LG, et al. (2010) Enhanced transrectal ultrasound modalities in the diagnosis of prostate cancer. Urology 76(5):1025–1033CrossRefGoogle Scholar
  31. 31.
    van Hove A, Savoie P-H, Maurin C, et al. (2014) Comparison of image-guided targeted biopsies versus systematic randomized biopsies in the detection of prostate cancer: a systematic literature review of well-designed studies. World J Urol 32(4):847–858CrossRefGoogle Scholar
  32. 32.
    Kuru TH, Fütterer JJ, Schiffmann J, et al. (2015) Transrectal ultrasound (US), contrast-enhanced US, real-time elastography, HistoScanning, magnetic resonance imaging (MRI), and MRI-US fusion biopsy in the diagnosis of prostate cancer. Eur Urol Focus 1(2):117–126CrossRefGoogle Scholar
  33. 33.
    Madsen HHT, Rasmussen F (2011) Contrast-enhanced ultrasound in oncology. Cancer Imaging 11(1A):S167CrossRefGoogle Scholar
  34. 34.
    Huang DY, Yusuf GT, Daneshi M, et al. (2016) Contrast-enhanced US–guided interventions: improving success rate and avoiding complications using US contrast agents. RadioGraphics 37(2):652–664CrossRefGoogle Scholar
  35. 35.
    Minami Y, Kudo M, Kawasaki T, et al. (2004) Treatment of hepatocellular carcinoma with percutaneous radiofrequency ablation: usefulness of contrast harmonic sonography for lesions poorly defined with B-mode sonography. Am J Roentgenol 183(1):153–156CrossRefGoogle Scholar
  36. 36.
    Hocke M, Menges M, Topalidis T, et al. (2008) Contrast-enhanced endoscopic ultrasound in discrimination between benign and malignant mediastinal and abdominal lymph nodes. J Cancer Res Clin Oncol 134(4):473–480CrossRefGoogle Scholar
  37. 37.
    Sever AR, Mills P, Jones SE, et al. (2011) Preoperative sentinel node identification with ultrasound using microbubbles in patients with breast cancer. Am J Roentgenol 196(2):251–256CrossRefGoogle Scholar
  38. 38.
    Kono Y, Lucidarme O, Choi S-H, et al. (2007) Contrast-enhanced ultrasound as a predictor of treatment efficacy within 2 weeks after transarterial chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 18(1):57–65CrossRefGoogle Scholar
  39. 39.
    Shaw CM, Eisenbrey JR, Lyshchik A, et al. (2015) Contrast-enhanced ultrasound evaluation of residual blood flow to hepatocellular carcinoma after treatment with transarterial chemoembolization using drug-eluting beads. J Ultrasound Med 34(5):859–867CrossRefGoogle Scholar
  40. 40.
    Iqbal SI, Stuart KE (2018) Assessment of tumor response in patients receiving systemic and nonsurgical locoregional treatment of hepatocellular cancer. In: Goldberg RM (ed) UpToDate. Waltham: UpToDateGoogle Scholar
  41. 41.
    Hines-Peralta A, Goldberg SN (2016) Radiofrequency ablation and cryoablation of renal cell carcinoma. In: Ross ME (ed) UpToDate. Waltham: UpToDate IncGoogle Scholar
  42. 42.
    Barwari K, Wijkstra H, van Delden OM, et al. (2013) Contrast-enhanced ultrasound for the evaluation of the cryolesion after laparoscopic renal cryoablation: an initial report. J Endourol 27(4):402–407CrossRefGoogle Scholar
  43. 43.
    Sanz E, Hevia V, Arias F, et al. (2015) Contrast-enhanced ultrasound (CEUS): an excellent tool in the follow-up of small renal masses treated with cryoablation. Curr Urol Rep 16(1):1–5CrossRefGoogle Scholar
  44. 44.
    Zeccolini G, Del Biondo D, Cicero C, et al. (2014) Comparison of contrast-enhanced ultrasound scan (CEUS) and MRI in the follow-up of cryoablation for small renal tumors. Exp 25 Cases . CrossRefGoogle Scholar
  45. 45.
    Eisenbrey JR, Shaw CM, Lyshchik A, et al. (2015) Contrast-enhanced subharmonic and harmonic ultrasound of renal masses undergoing percutaneous cryoablation. Acad Radiol 22(7):820–826CrossRefGoogle Scholar
  46. 46.
    Chen M-H, Yang W, Yan K, et al. (2004) Large liver tumors: protocol for radiofrequency ablation and its clinical application in 110 patients—mathematic model, overlapping mode, and electrode placement process. Radiology 232(1):260–271CrossRefGoogle Scholar
  47. 47.
    Roccarina D, Garcovich M, Ainora ME, et al. (2015) Usefulness of contrast enhanced ultrasound in monitoring therapeutic response after hepatocellular carcinoma treatment. World J Hepatol 7(14):1866CrossRefGoogle Scholar
  48. 48.
    Du J, Li H-L, Zhai B, et al. (2015) Radiofrequency ablation for hepatocellular carcinoma: utility of conventional ultrasound and contrast-enhanced ultrasound in guiding and assessing early therapeutic response and short-term follow-up results. Ultrasound Med Biol 41(9):2400–2411CrossRefGoogle Scholar
  49. 49.
    Hoeffel C, Pousset M, Timsit M-O, et al. (2010) Radiofrequency ablation of renal tumours: diagnostic accuracy of contrast-enhanced ultrasound for early detection of residual tumour. Eur Radiol 20(8):1812–1821CrossRefGoogle Scholar
  50. 50.
    Dill-Macky MJ, Asch M, Burns P, et al. (2006) Radiofrequency ablation of hepatocellular carcinoma: predicting success using contrast-enhanced sonography. Am J Roentgenol 186(5):S287–S295CrossRefGoogle Scholar
  51. 51.
    Hou X, Jin Z, Xu C, et al. (2015) Contrast-enhanced harmonic endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic lesions: a retrospective study. PLoS ONE 10(3):e0121236CrossRefGoogle Scholar
  52. 52.
    Seicean A, Badea R, Moldovan-Pop A, et al. (2017) Harmonic contrast-enhanced endoscopic ultrasonography for the guidance of fine-needle aspiration in solid pancreatic masses. Ultraschall in der Medizin-Eur J Ultrasound 38(02):174–182Google Scholar
  53. 53.
    Frauscher F, Klauser A, Volgger H, et al. (2002) Comparison of contrast enhanced color Doppler targeted biopsy with conventional systematic biopsy: impact on prostate cancer detection. J Urol 167(4):1648–1652CrossRefGoogle Scholar
  54. 54.
    Linden RA, Trabulsi EJ, Forsberg F, et al. (2007) Contrast enhanced ultrasound flash replenishment method for directed prostate biopsies. J Urol 178(6):2354–2358CrossRefGoogle Scholar
  55. 55.
    Mitterberger MJ, Aigner F, Horninger W, et al. (2010) Comparative efficiency of contrast-enhanced colour Doppler ultrasound targeted versus systematic biopsy for prostate cancer detection. Eur Radiol 20(12):2791–2796CrossRefGoogle Scholar
  56. 56.
    Taverna G, Morandi G, Seveso M, et al. (2011) Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling. BJU Int 108(11):1723–1727CrossRefGoogle Scholar
  57. 57.
    Zhao H-X, Xia C-X, Yin H-X, et al. (2013) The value and limitations of contrast-enhanced transrectal ultrasonography for the detection of prostate cancer. Eur J Radiol 82(11):e647CrossRefGoogle Scholar
  58. 58.
    Meloni MF, Bertolotto M, Alberzoni C, et al. (2008) Follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: contrast-enhanced sonography versus contrast-enhanced CT or MRI. Am J Roentgenol 191(4):1233–1238CrossRefGoogle Scholar
  59. 59.
    Kong W-T, Zhang W-W, Guo H-Q, et al. (2011) Application of contrast-enhanced ultrasonography after radiofrequency ablation for renal cell carcinoma: is it sufficient for assessment of therapeutic response? Abdom Imaging 36(3):342–347CrossRefGoogle Scholar
  60. 60.
    Li X, Liang P, Yu J, et al. (2013) Role of contrast-enhanced ultrasound in evaluating the efficiency of ultrasound guided percutaneous microwave ablation in patients with renal cell carcinoma. Radiol Oncol 47(4):398–404CrossRefGoogle Scholar
  61. 61.
    Garbajs M, Popovic P (2016) Contrast-enhanced ultrasound for assessment of therapeutic response after percutaneous radiofrequency ablation of small renal tumors. Age (years) 77:58–94Google Scholar
  62. 62.
    Meloni MF, Goldberg SN, Livraghi T, et al. (2001) Hepatocellular carcinoma treated with radiofrequency ablation: comparison of pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power Doppler sonography, and helical CT. Am J Roentgenol 177(2):375–380CrossRefGoogle Scholar
  63. 63.
    Choi D, Lim HK, Lee WJ, et al. (2003) Early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma. J Ultrasound Med 22(11):1163–1172CrossRefGoogle Scholar
  64. 64.
    Wen YL, Kudo M, Zheng RQ, et al. (2003) Radiofrequency ablation of hepatocellular carcinoma: therapeutic response using contrast-enhanced coded phase-inversion harmonic sonography. Am J Roentgenol 181(1):57–63CrossRefGoogle Scholar
  65. 65.
    Kim CK, Choi D, Lim HK, et al. (2005) Therapeutic response assessment of percutaneous radiofrequency ablation for hepatocellular carcinoma: utility of contrast-enhanced agent detection imaging. Eur J Radiol 56(1):66–73CrossRefGoogle Scholar
  66. 66.
    Yu X-L, Li A-H, Jiang T-A, et al. (2007) Comparison of contrast enhanced ultrasound and contrast enhanced CT or MRI in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma: a multi-center study in China. Ultrasound Med Biol 33(11):1736–1749CrossRefGoogle Scholar
  67. 67.
    Salvaggio G, Campisi A, Greco VL, et al. (2010) Evaluation of posttreatment response of hepatocellular carcinoma: comparison of ultrasonography with second-generation ultrasound contrast agent and multidetector CT. Abdom Imaging 35(4):447–453CrossRefGoogle Scholar
  68. 68.
    Bo X-W, Xu H-X, Sun L-P, et al. (2014) Bipolar radiofrequency ablation for liver tumors: comparison of contrast-enhanced ultrasound with contrast-enhanced MRI/CT in the posttreatment imaging evaluation. Int J Clin Exp Pathol 7(9):6108PubMedPubMedCentralGoogle Scholar
  69. 69.
    Minami Y, Kudo M, Kawasaki T, et al. (2003) Transcatheter arterial chemoembolization of hepatocellular carcinoma: usefulness of coded phase-inversion harmonic sonography. Am J Roentgenol 180(3):703–708CrossRefGoogle Scholar
  70. 70.
    Kim HJ, Kim TK, Kim PN, et al. (2006) Assessment of the therapeutic response of hepatocellular carcinoma treated with transcatheter arterial chemoembolization. J Ultrasound Med 25(4):477–486CrossRefGoogle Scholar
  71. 71.
    Xia Y, Kudo M, Minami Y, et al. (2008) Response evaluation of transcatheter arterial chemoembolization in hepatocellular carcinomas: the usefulness of sonazoid-enhanced harmonic sonography. Oncology 75(1):99–105CrossRefGoogle Scholar
  72. 72.
    Morimoto M, Shirato K, Sugimori K, et al. (2003) Contrast-enhanced harmonic gray-scale sonographic–histologic correlation of the therapeutic effects of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Am J Roentgenol 181(1):65–69CrossRefGoogle Scholar
  73. 73.
    Liu M, Lin M-X, Xu Z-F, et al. (2015) Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography in evaluating the treatment response to transcatheter arterial chemoembolization of hepatocellular carcinoma using modified RECIST. Eur Radiol 25(8):2502–2511CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of SurgeryLankenau Medical CenterWynnewoodUSA
  2. 2.Department of RadiologyThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations