Skip to main content
SpringerLink
Log in

Contrast-enhanced endoscopic ultrasonography in digestive diseases

  • Review
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Contrast-enhanced endoscopic ultrasonography (CE-EUS) was introduced in the early 1990s. The concept of the injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) led to “endoscopic ultrasonographic angiography”. After the arrival of the first-generation contrast agent, high-frequency (12 MHz) EUS brought about the enhancement of EUS images in the diagnosis of pancreatico-biliary diseases, upper gastrointestinal (GI) cancer, and submucosal tumors. The electronic scanning endosonoscope with both radial and linear probes enabled the use of high-end ultrasound machines and depicted the enhancement of both color/power Doppler flow-based imaging and harmonic-based imaging using second-generation contrast agents. Many reports have described the usefulness of the differential diagnosis of pancreatic diseases and other abdominal lesions. Quantitative evaluation of CE-EUS images was an objective method of diagnosis using the time-intensity curve (TIC), but it was limited to the region of interest. Recently developed Inflow Time Mapping™ can be generated from stored clips and used to display the pattern of signal enhancement with time after injection, offering temporal difference of contrast agents and improved tumor characterization. On the other hand, three-dimensional CE-EUS images added new information to the literature, but lacked positional information. Three-dimensional CE-EUS with accurate positional information is awaited. To date, most reports have been related to pancreatic lesions or lymph nodes. Hemodynamic analysis might be of use for diseases in other organs: upper GI cancer diagnosis, submucosal tumors, and biliary disorders, and it might also provide functional information. Studies of CE-EUS in diseases in many other organs will increase in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Matsuda Y, Yabuuchi I. Hepatic tumors: US contrast enhancement with CO2 microbubbles. Radiology. 1986;161(3):701–5.

    PubMed  CAS  Google Scholar 

  2. Hirooka Y, Naitoh Y, Goto H, Ito A, Taki T, Hayakawa T. Usefulness of contrast-enhanced endoscopic ultrasonography with intravenous injection of sonicated serum albumin. Gastrointest Endosc. 1997;46(2):166–9.

    Article  PubMed  CAS  Google Scholar 

  3. Kato T, Tsukamoto Y, Naitoh Y, Hirooka Y, Furukawa T, Hayakawa T. Ultrasonographic and endoscopic ultrasonographic angiography in pancreatic mass lesions. Acta Radiol. 1995;36(4):381–7.

    PubMed  CAS  Google Scholar 

  4. Kuroiwa M, Tsukamoto Y, Naitoh Y, Hirooka Y, Furukawa T, Katou T. New technique using intraductal ultrasonography for the diagnosis of bile duct cancer. J Ultrasound Med. 1994;13(3):189–95.

    PubMed  CAS  Google Scholar 

  5. Reddy NK, Ioncica AM, Saftoiu A, Vilmann P, Bhutani MS. Contrast-enhanced endoscopic ultrasonography. World J Gastroenterol. 2011;17(1):42–8.

    Article  PubMed  Google Scholar 

  6. Bhutani MS, Hoffman BJ, van Velse A, Hawes RH. Contrast-enhanced endoscopic ultrasonography with galactose microparticles: SHU508 A (Levovist). Endoscopy. 1997;29(7):635–9.

    Article  PubMed  CAS  Google Scholar 

  7. Hirooka Y, Goto H, Ito A, Hayakawa S, Watanabe Y, Ishiguro Y, et al. Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a preliminary study. Am J Gastroenterol. 1998;93(4):632–5.

    Article  PubMed  CAS  Google Scholar 

  8. Hirooka Y, Naitoh Y, Goto H, Ito A, Hayakawa S, Watanabe Y, et al. Contrast-enhanced endoscopic ultrasonography in gallbladder diseases. Gastrointest Endosc. 1998;48(4):406–10.

    Article  PubMed  CAS  Google Scholar 

  9. Nomura N, Goto H, Niwa Y, Arisawa T, Hirooka Y, Hayakawa T. Usefulness of contrast-enhanced EUS in the diagnosis of upper GI tract diseases. Gastrointest Endosc. 1999;50(4):555–60.

    Article  PubMed  CAS  Google Scholar 

  10. Sakamoto H, Kitano M, Matsui S, Kamata K, Komaki T, Imai H, et al. Estimation of malignant potential of GI stromal tumors by contrast-enhanced harmonic EUS (with videos). Gastrointest Endosc. 2011;73(2):227–37.

    Article  PubMed  Google Scholar 

  11. Niwa K, Hirooka Y, Itoh A, Hashimoto S, Hirai T, Takeda K, et al. Preclinical study of endoscopic ultrasonography with electronic radial scanning echoendoscope. J Gastroenterol Hepatol. 2003;18(7):828–35.

    Article  PubMed  Google Scholar 

  12. Niwa K, Hirooka Y, Niwa Y, Itoh A, Ohmiya N, Hashimoto S, et al. Comparison of image quality between electronic and mechanical radial scanning echoendoscopes in pancreatic diseases. J Gastroenterol Hepatol. 2004;19(4):454–9.

    Article  PubMed  Google Scholar 

  13. Ishikawa H, Hirooka Y, Itoh A, Hashimoto S, Okada N, Itoh T, et al. A comparison of image quality between tissue harmonic imaging and fundamental imaging with an electronic radial scanning echoendoscope in the diagnosis of pancreatic diseases. Gastrointest Endosc. 2003;57(7):931–6.

    Article  PubMed  Google Scholar 

  14. Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and power-Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma. Gastrointest Endosc. 2001;53(7):784–9.

    Article  PubMed  CAS  Google Scholar 

  15. Hocke M, Schulze E, Gottschalk P, Topalidis T, Dietrich CF. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol. 2006;12(2):246–50.

    PubMed  Google Scholar 

  16. Kanamori A, Hirooka Y, Itoh A, Hashimoto S, Kawashima H, Hara K, et al. Usefulness of contrast-enhanced endoscopic ultrasonography in the differentiation between malignant and benign lymphadenopathy. Am J Gastroenterol. 2006;101(1):45–51.

    Article  PubMed  Google Scholar 

  17. Dietrich CF, Ignee A, Braden B, Barreiros AP, Ott M, Hocke M. Improved differentiation of pancreatic tumors using contrast-enhanced endoscopic ultrasound. Clin Gastroenterol Hepatol. 2008;6(5):590–7.

    Article  PubMed  Google Scholar 

  18. Hocke M, Menges M, Topalidis T, Dietrich CF, Stallmach A. Contrast-enhanced endoscopic ultrasound in discrimination between benign and malignant mediastinal and abdominal lymph nodes. J Cancer Res Clin Oncol. 2008;134(4):473–80.

    Article  PubMed  Google Scholar 

  19. Hocke M, Schmidt C, Zimmer B, Topalidis T, Dietrich CF, Stallmach A. Contrast enhanced endosonography for improving differential diagnosis between chronic pancreatitis and pancreatic cancer. Dtsch Med Wochenschr. 2008;133(38):1888–92.

    Article  PubMed  CAS  Google Scholar 

  20. Hirooka Y, Itoh A, Kawashima H, Ohno E, Ishikawa T, Matsubara H, et al. Diagnosis of pancreatic disorders using contrast-enhanced endoscopic ultrasonography and endoscopic elastography. Clin Gastroenterol Hepatol. 2009;7:S63–7.

    Article  PubMed  Google Scholar 

  21. Ohno E, Hirooka Y, Itoh A, Ishigami M, Katano Y, Ohmiya N, et al. Intraductal papillary mucinous neoplasms of the pancreas: differentiation of malignant and benign tumors by endoscopic ultrasound findings of mural nodules. Ann Surg. 2009;249(4):628–34.

    Article  PubMed  Google Scholar 

  22. Saftoiu A, Vilmann P. Role of endoscopic ultrasound in the diagnosis and staging of pancreatic cancer. J Clin Ultrasound. 2009;37(1):1–17.

    Article  PubMed  Google Scholar 

  23. Giovannini M. The place of endoscopic ultrasound in bilio-pancreatic pathology. Gastroenterol Clin Biol. 2010;34(8–9):436–45.

    Article  PubMed  CAS  Google Scholar 

  24. Ishikawa T, Itoh A, Kawashima H, Ohno E, Matsubara H, Itoh Y, et al. Usefulness of EUS combined with contrast-enhancement in the differential diagnosis of malignant versus benign and preoperative localization of pancreatic endocrine tumors. Gastrointest Endosc. 2010;71(6):951–9.

    Article  PubMed  Google Scholar 

  25. Saftoiu A, Iordache SA, Gheonea DI, Popescu C, Malos A, Gorunescu F, et al. Combined contrast-enhanced power Doppler and real-time sonoelastography performed during EUS, used in the differential diagnosis of focal pancreatic masses (with videos). Gastrointest Endosc. 2010;72(4):739–47.

    Article  PubMed  Google Scholar 

  26. Hirooka Y, Itoh A, Kawashima H, Ohno E, Ishikawa T, Itoh Y, et al. Clinical oncology for pancreatic and biliary cancers: advances and current limitations. World J Clin Oncol. 2011;2(5):217–24.

    PubMed  Google Scholar 

  27. Hocke M, Ignee A, Dietrich CF. Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis. Endoscopy. 2011;43(2):163–5.

    Article  PubMed  CAS  Google Scholar 

  28. Kitano M, Kudo M, Sakamoto H, Komaki T. Endoscopic ultrasonography and contrast-enhanced endoscopic ultrasonography. Pancreatology. 2011;11(Suppl 2):28–33.

    Article  PubMed  Google Scholar 

  29. Ohno E, Itoh A, Kawashima H, Ishikawa T, Matsubara H, Itoh Y, et al. Malignant transformation of branch duct-type intraductal papillary mucinous neoplasms of the pancreas based on contrast-enhanced endoscopic ultrasonography morphological changes: focus on malignant transformation of intraductal papillary mucinous neoplasm itself. Pancreas. 2012;41(6):855–62.

    Article  PubMed  Google Scholar 

  30. Sakamoto H, Kitano M, Suetomi Y, Maekawa K, Takeyama Y, Kudo M. Utility of contrast-enhanced endoscopic ultrasonography for diagnosis of small pancreatic carcinomas. Ultrasound Med Biol. 2008;34(4):525–32.

    Article  PubMed  Google Scholar 

  31. Dietrich CF, Ignee A, Frey H. Contrast-enhanced endoscopic ultrasound with low mechanical index: a new technique. Z Gastroenterol. 2005;43(11):1219–23.

    Article  PubMed  CAS  Google Scholar 

  32. Kitano M, Sakamoto H, Matsui U, Ito Y, Maekawa K, von Schrenck T, et al. A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2008;67(1):141–50.

    Article  PubMed  Google Scholar 

  33. Imazu H, Uchiyama Y, Matsunaga K, Ikeda K, Kakutani H, Sasaki Y, et al. Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies. Scand J Gastroenterol. 2010;45(6):732–8.

    Article  PubMed  Google Scholar 

  34. Napoleon B, Alvarez-Sanchez MV, Gincoul R, Pujol B, Lefort C, Lepilliez V, et al. Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. Endoscopy. 2010;42(7):564–70.

    Article  PubMed  CAS  Google Scholar 

  35. Sakamoto H, Kitano M, Kamata K, El-Masry M, Kudo M. Diagnosis of pancreatic tumors by endoscopic ultrasonography. World J Radiol. 2010;2(4):122–34.

    Article  PubMed  Google Scholar 

  36. Seicean A, Badea R, Stan-Iuga R, Gulei I, Pop T, Pascu O. The added value of real-time harmonics contrast-enhanced endoscopic ultrasonography for the characterisation of pancreatic diseases in routine practice. J Gastrointestin Liver Dis. 2010;19(1):99–104.

    PubMed  Google Scholar 

  37. Seicean A, Badea R, Stan-Iuga R, Mocan T, Gulei I, Pascu O. Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses. Ultraschall Med. 2010;31(6):571–6.

    Article  PubMed  CAS  Google Scholar 

  38. Xia Y, Kitano M, Kudo M, Imai H, Kamata K, Sakamoto H, et al. Characterization of intra-abdominal lesions of undetermined origin by contrast-enhanced harmonic EUS (with videos). Gastrointest Endosc. 2010;72(3):637–42.

    Article  PubMed  Google Scholar 

  39. Hijioka S, Sawaki A, Mizuno N, Hara K, Mekky MA, El-Amin H, et al. Contrast-enhanced endoscopic ultrasonography (CE-EUS) findings in adrenal metastasis from renal cell carcinoma. J Med Ultrason. 2011;38(2):89–92.

    Article  Google Scholar 

  40. Kitano M, Sakamoto H, Komaki T, Kudo M. New techniques and future perspective of EUS for the differential diagnosis of pancreatic malignancies: contrast harmonic imaging. Dig Endosc. 2011;23(Suppl 1):46–50.

    Article  PubMed  Google Scholar 

  41. Matsubara H, Itoh A, Kawashima H, Kasugai T, Ohno E, Ishikawa T, et al. Dynamic quantitative evaluation of contrast-enhanced endoscopic ultrasonography in the diagnosis of pancreatic diseases. Pancreas. 2011;40(7):1073–9.

    Article  PubMed  Google Scholar 

  42. Romagnuolo J, Hoffman B, Vela S, Hawes R, Vignesh S. Accuracy of contrast-enhanced harmonic EUS with a second-generation perflutren lipid microsphere contrast agent (with video). Gastrointest Endosc. 2011;73(1):52–63.

    Article  PubMed  Google Scholar 

  43. Imazu H, Kanazawa K, Mori N, Ikeda K, Kakutani H, Sumiyama K, et al. Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma. Scand J Gastroenterol. 2012;47(7):853–60.

    Article  PubMed  Google Scholar 

  44. Kitano M, Kudo M, Yamao K, Takagi T, Sakamoto H, Komaki T, et al. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012;107(2):303–10.

    Article  PubMed  Google Scholar 

  45. Kitano M, Sakamoto H, Kudo M. Endoscopic ultrasound: contrast enhancement. Gastrointest Endosc Clin N Am. 2012;22(2):349–58.

    Article  PubMed  Google Scholar 

  46. Giovannini M. Contrast-enhanced endoscopic ultrasound and elastosonoendoscopy. Best Pract Res Clin Gastroenterol. 2009;23(5):767–79.

    Article  PubMed  Google Scholar 

  47. Tanaka M, Jang JY, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12(3):183–97.

    PubMed  Google Scholar 

  48. Calliada F, Campani R, Bottinelli O, Bozzini A, Sommaruga MG. Ultrasound contrast agents: basic principles. Eur J Radiol. 1998;27(Suppl 2):S157–60.

    Article  PubMed  Google Scholar 

  49. Saftoiu A, Gheonea DI. Tridimensional (3D) endoscopic ultrasound—a pictorial review. J Gastrointestin Liver Dis. 2009;18(4):501–5.

    PubMed  Google Scholar 

  50. Giovannini M. Contrast-enhanced and 3-dimensional endoscopic ultrasonography. Gastroenterol Clin North Am. 2010;39(4):845–58.

    Article  PubMed  Google Scholar 

  51. Hocke M, Dietrich CF. New technology–combined use of 3D contrast enhanced endoscopic ultrasound techniques. Ultraschall Med. 2011;32(3):317–8.

    Article  PubMed  Google Scholar 

  52. Hocke M, Ignee A, Dietrich CF. Three-dimensional contrast-enhanced endoscopic ultrasound for the diagnosis of autoimmune pancreatitis. Endoscopy. 2011;43:Suppl 2 UCTN:E381-2.

    Google Scholar 

  53. Pochon S, Tardy I, Bussat P, Bettinger T, Brochot J, von Wronski M, et al. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol. 2010;45(2):89–95.

    Article  PubMed  CAS  Google Scholar 

  54. Anderson CR, Hu X, Zhang H, Tlaxca J, Decleves AE, Houghtaling R, et al. Ultrasound molecular imaging of tumor angiogenesis with an integrin targeted microbubble contrast agent. Invest Radiol. 2011;46(4):215–24.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Endoscopy, Nagoya University Hospital, 65 Tsuruma-Cho, Showa-ku, Nagoya City, Japan

    Yoshiki Hirooka, Eizaburo Ohno, Yosuke Nakamura, Kohei Funasaka & Hidemi Goto

  2. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-ku, Nagoya City, Japan

    Akihiro Itoh, Hiroki Kawashima, Yuya Itoh, Takeshi Hiramatsu, Hiroyuki Sugimoto, Hajime Sumi, Daijiro Hayashi, Naoki Ohmiya, Ryoji Miyahara, Masanao Nakamura, Masatoshi Ishigami, Yoshiaki Katano & Hidemi Goto

Authors
  1. Yoshiki Hirooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akihiro Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroki Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eizaburo Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuya Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yosuke Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeshi Hiramatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroyuki Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hajime Sumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daijiro Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Naoki Ohmiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ryoji Miyahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masanao Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kohei Funasaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masatoshi Ishigami
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yoshiaki Katano
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hidemi Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshiki Hirooka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirooka, Y., Itoh, A., Kawashima, H. et al. Contrast-enhanced endoscopic ultrasonography in digestive diseases. J Gastroenterol 47, 1063–1072 (2012). https://doi.org/10.1007/s00535-012-0662-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-012-0662-4

Keywords

Search

Navigation