Endosonography, Contrast Agents, and Elastography

  • Masayuki KitanoEmail author
  • Kosuke Minaga
  • Masatoshi Kudo


Recent advances in endoscopic ultrasonography (EUS) imaging technology has led to the evolution of the image-enhanced EUS modalities called contrast-enhanced EUS and EUS elastography. These modalities can depict tissue structure in detail and thus are clinically useful for diagnosing pancreatobiliary and upper gastrointestinal diseases. Moreover, they complement EUS-guided fine-needle aspiration (EUS-FNA) by correctly diagnosing lesions with EUS-FNA false-negative findings and by identifying the most appropriate target site of EUS-FNA. This chapter focuses on the upcoming techniques of imaging in the field of EUS and how these techniques improve the diagnostic ability of EUS, particularly in terms of characterizing conventional EUS-detected lesions.


Ultrasound contrast agents Contrast-enhanced endoscopic ultrasound Endoscopic ultrasonography Elastography Elasticity imaging Pancreatobiliary diseases 



Area under ROC curve


Chronic pancreatitis


Computed tomography


Endoscopic ultrasonography


Fine-needle aspiration


Gastrointestinal stromal tumors


Negative predictive value


Pancreatic exocrine insufficiency


Positive predictive value


Primary sclerosing cholangitis


Region of interest


Subepithelial tumors


Strain ratio


Time–intensity curve


Ultrasound contrast agents

Supplementary material

Video 11.1

Endoscopic ultrasonography (EUS) image of a branch-duct type malignant intraductal papillary mucinous neoplasm in the head of the pancreas. EUS reveals a multilocular cystic lesion of 40 mm in diameter. A 15 × 12 mm mural nodule is depicted inside the cystic lesion. After infusion of UCA, contrast-enhanced harmonic EUS image shows that the mural nodule has abundant vascularity (MOV 10298 kb)

Video 11.2

Endoscopic ultrasonography (EUS) image of a gallbladder adenocarcinoma. EUS reveals a 30 × 13 mm low echoic mass lesion in the body of the gallbladder. After infusion of UCA, contrast-enhanced harmonic EUS indicates that the lesion exhibits heterogeneous enhancement with intratumoral irregular vessels (MP4 23389 kb)

Video 11.3

Endoscopic ultrasonography (EUS) image of a liver metastasis of a pancreatic carcinoma. Left image shows conventional EUS image, and right image shows EUS elastography image. EUS elastography depicts a nodule of 6 mm in diameter which shows relatively homogenous hard pattern (predominant blue pattern) in the liver (right). However, conventional EUS cannot identify the nodule (left) (MOV 3274 kb)

Video 11.4

Endoscopic ultrasonography (EUS) image and contrast-enhanced harmonic EUS-guided fine-needle aspiration of a malignant intra-abdominal lymph node. EUS reveals a low echoic lesion of 40 mm in diameter around the aorta. After infusion of UCA, contrast-enhanced harmonic EUS indicates that the lesion exhibits heterogeneous enhancement with avascular area. On real-time imaging with contrast-enhancement EUS, the site with hyperenhancement in the lesion is punctured with a 22-gauge EUS-FNA needle, which revealed a lymph node metastasis of neuroendocrine carcinoma (MP4 21721 kb)


  1. 1.
    Rösch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. 1992;326:1721–6.CrossRefPubMedGoogle Scholar
  2. 2.
    DeWitt J, Devereaux B, Chriswell M, et al. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004;141:753–63.CrossRefPubMedGoogle Scholar
  3. 3.
    Khashab MA, Yong E, Lennon AM, et al. EUS is still superior to multidetector computed tomography for detection of pancreatic neuroendocrine tumors. Gastrointest Endosc. 2011;7:691–6.CrossRefGoogle Scholar
  4. 4.
    Dietrich CF, Ignee A, Frey H. Contrast-enhanced endoscopic ultrasound with low mechanical index: a new technique. Z Gastroenterol. 2005;43:1219–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Kitano M, Sakamoto H, Matsui U, et al. A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2008;67:141–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Săftoiu A, Vilman P, Dietrich CF, et al. Quantitative contrast-enhanced harmonic EUS in differential diagnosis of focal pancreatic masses. Gastrointest Endosc. 2015;82:59–69.CrossRefPubMedGoogle Scholar
  7. 7.
    Săftoiu A, Vilman P. Endoscopic ultrasound elastography—a new imaging technique for the visualization of tissue elasticity distribution. J Gastrointestin Liver Dis. 2006;15:161–5.PubMedGoogle Scholar
  8. 8.
    Giovannini M, Hookey LC, Bories E, et al. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy. 2006;38:344–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Quaia E. Classification and safety of microbubble-based contrast agents. In: Quaia E, editor. Contrast media in ultrasonography. basic principles and clinical applications. Berlin: Springer; 2005. p. 1–14.CrossRefGoogle Scholar
  10. 10.
    Sontum PC. Physiochemical characteristics of Sonazoid, a new contrast agent for ultrasound imaging. Ultrasound Med Biol. 2008;34:824–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Kitano M, Kamata K, Imai H, et al. Contrast-enhanced harmonic endoscopic ultrasonography for pancreatobiliary diseases. Dig Endosc. 2015;27 Suppl 1:60–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Whittingham TA. Contrast-specific imaging techniques; technical perspective. In: Quaia E, editor. Contrast media in ultrasonography. Basic principles and clinical applications. Berlin: Springer; 2005. p. 43–84.CrossRefGoogle Scholar
  13. 13.
    Kitano M, Kudo M, Sakamoto H, et al. Preliminary study of contrast-enhanced harmonic endosonography with second-generation contrast agents. J Med Ultrason. 2008;35:11–8.CrossRefGoogle Scholar
  14. 14.
    Becker D, Strobel D, Bernatik T, et al. Echo-enhanced color and power-Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma. Gastrointest Endosc. 2001;53:784–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Hocke M, Schulze E, Gottschalk P, et al. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol. 2006;12:246–50.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Sakamoto H, Kitano M, Suetomi Y, et al. Utility of contrastenhanced endoscopic ultrasonography for diagnosis of small pancreatic carcinomas. Ultrasound Med Biol. 2008;34:525–32.CrossRefPubMedGoogle Scholar
  17. 17.
    Das K, Kudo M, Kitano M, et al. Diagnostic value of endoscopic ultrasound-guided directional eFLOW in solid pancreatic lesions. J Med Ultrason. 2013;40:211–8.CrossRefGoogle Scholar
  18. 18.
    Dietrich CF, Ignee A, Braden B, et al. Improved differentiation of pancreatic tumors using contrast-enhanced endoscopic ultrasound. Clin Gastroenterol Hepatol. 2008;6:590–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Ishikawa T, Itoh A, Kawashima H, 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;71:951–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Wilson SR, Greenbaum LD, Goldberg BB. Contrast-enhanced ultrasound: what is the evidence and what are the obstacles? AJR Am J Roentgenol. 2009;193:55–60.CrossRefPubMedGoogle Scholar
  21. 21.
    Ophir J, Cespedes I, Ponnekanti H, Yazdi Y, Li X. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason Imaging. 1991;13:111–34.CrossRefPubMedGoogle Scholar
  22. 22.
    Lerner RM, Huang SR, Parker KJ. “Sonoelasticity” images derived from ultrasound signals in mechanically vibrated tissues. Ultrasound Med Biol. 1990;16:231–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Ophir J, Cespedes EI, Garra BS, et al. Elastography: ultrasonic imaging of tissue strain and elastic modulus in vivo. Eur J Ultrasound. 1996;3:49–70.CrossRefGoogle Scholar
  24. 24.
    Doyley MM, Meaney PM, Bamber JC. Evaluation of an iterative reconstruction method for quantitative elastography. Phys Med Biol. 2000;45:1521–40.CrossRefPubMedGoogle Scholar
  25. 25.
    Janssen J, Schlorer E, Greiner L, et al. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrointest Endosc. 2007;65:971–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Giovannini M, Thomas B, Erwan B, et al. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study. World J Gastroenterol. 2009;15:1587–93.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. EUS elastography for the characterization of solid pancreatic masses. Gastrointest Endosc. 2009;70:1101–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Itokawa F, Itoi T, Sofuni A, et al. EUS elastography combined with the strain ratio of tissue elasticity for diagnosis of solid pancreatic masses. J Gastroenterol. 2011;46:843–53.CrossRefPubMedGoogle Scholar
  29. 29.
    Hocke M, Ignee A, Dietrich CF. Advanced endosonographic diagnostic tools for discrimination of focal chronic pancreatitis and pancreatic carcinoma-elastography, contrast enhanced high mechanical index (CEHMI) and low mechanical index (CELMI) endosonography in direct comparison. Z Gastroenterol. 2012;50:199–203.CrossRefPubMedGoogle Scholar
  30. 30.
    Mayerle J, Simon P, Dickson EJ, et al. The role of EUS guided elastography to diagnose solid pancreatic mass lesions. Pancreas. 2010;39:1334.Google Scholar
  31. 31.
    Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. Quantitative endoscopic ultrasound elastography: an accurate method for the differentiation of solid pancreatic masses. Gastroenterology. 2010;139:1172–80.CrossRefPubMedGoogle Scholar
  32. 32.
    Dawwas MF, Taha H, Leeds JS, et al. Diagnostic accuracy of quantitative EUS elastography for discriminating malignant from benign solid pancreatic masses: a prospective, single-center study. Gastrointest Endosc. 2012;76:953–61.CrossRefPubMedGoogle Scholar
  33. 33.
    Săftoiu A, Iordache SA, Gheonea DI, 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;72:739–47.CrossRefPubMedGoogle Scholar
  34. 34.
    Săftoiu A, Vilmann P, Gorunescu F, et al. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc. 2008;68:1086–94.CrossRefPubMedGoogle Scholar
  35. 35.
    Săftoiu A, Vilmann P, Gorunescu F, et al. Efficacy of an artificial neural network-based approach to endoscopic ultrasound elastography in diagnosis of focal pancreatic masses. Clin Gastroenterol Hepatol. 2012;10:84–90.CrossRefPubMedGoogle Scholar
  36. 36.
    Fusaroli P, Spada A, Mancino MG, et al. Contrast harmonic echo-endoscopic ultrasound improves accuracy in diagnosis of solid pancreatic masses. Clin Gastroenterol Hepatol. 2010;8:629–34.CrossRefPubMedGoogle Scholar
  37. 37.
    Kitano M, Kudo M, Yamao K, et al. Characterization of small solid tumors in the pancreas: the value of contrast enhanced harmonic endoscopic ultrasonography. Am J Gastroenterol. 2012;107:303–10.CrossRefPubMedGoogle Scholar
  38. 38.
    Romagnuolo J, Hoffman B, Vela S, et al. Accuracy of contrast enhanced harmonic EUS with a second-generation perflutren lipid microsphere contrast agent (with video). Gastrointest Endosc. 2011;73:52–63.CrossRefPubMedGoogle Scholar
  39. 39.
    Napoleon B, Alvarez-Sanchez MV, Gincoul R, et al. Contrast enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study. Endoscopy. 2010;42:564–70.CrossRefPubMedGoogle Scholar
  40. 40.
    Gincul R, Palazzo M, Pujol B, et al. Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial. Endoscopy. 2014;46:373–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Gong TT, Hu DM, Zhu Q. Contrast-enhanced EUS for differential diagnosis of pancreatic mass lesions: a meta-analysis. Gastrointest Endosc. 2012;76:301–9.CrossRefPubMedGoogle Scholar
  42. 42.
    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;31:571–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Imazu H, Kanazawa K, Mori N, et al. Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma. Scand J Gastroenterol. 2012;47:853–60.CrossRefPubMedGoogle Scholar
  44. 44.
    Gheonea DI, Streba CT, Ciurea T, Săftoiu A. Quantitative low mechanical index contrast enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastroenterol. 2013;13:2.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Matsubara H, Itoh A, Kawashima H, et al. Dynamic quantitative evaluation of contrast enhanced endoscopic ultrasonography in the diagnosis of pancreatic diseases. Pancreas. 2011;40:1073–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Pei Q, Zou X, Zhang X, et al. Diagnostic value of EUS elastography in differentiation of benign and malignant solid pancreatic masses: a meta-analysis. Pancreatology. 2012;12:402–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Mei M, Ni J, Liu D, et al. EUS elastography for diagnosis of solid pancreatic masses: a meta-analysis. Gastrointest Endosc. 2013;77:578–89.CrossRefPubMedGoogle Scholar
  48. 48.
    Koito K, Namieno T, Nagakawa T, et al. Solitary cystic tumor of the pancreas: EUS-pathologic correlation. Gastrointest Endosc. 1997;45:268–76.CrossRefPubMedGoogle Scholar
  49. 49.
    Kubo H, Nakamura K, Itaba S, et al. Differential diagnosis of cystic tumors of the pancreas by endoscopic ultrasonography. Endoscopy. 2009;41:684–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Hocke M, Cui XW, Domagk D, et al. Pancreatic cystic lesions: the value of contrast-enhanced endoscopic ultrasound to influence the clinical pathway. Endosc Ultrasound. 2014;3:123–30.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Yamashita Y, Ueda K, Itonaga M, et al. Usefulness of contrast-enhanced endoscopic ultrasonography for discriminating mural nodules from mucous clots in intraductul papillary mucinous neoplasms; a single-center prospective study. J Ultrasound Med. 2013;32:61–8.PubMedGoogle Scholar
  52. 52.
    Kamata K, Kitano M, Omoto S, et al. Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of pancreatic cysts. Endoscopy. 2016;48(1):35–41.PubMedGoogle Scholar
  53. 53.
    Ohno E, Hirooka Y, Itoh A, 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;249:628–34.CrossRefPubMedGoogle Scholar
  54. 54.
    Iglesias-Garcia J, Domínguez-Muñoz JE, Castiñeira-Alvariño M, et al. Quantitative elastography associated with endoscopic ultrasound for the diagnosis of chronic pancreatitis. Endoscopy. 2013;45:781–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Janssen J, Papavassiliou I. Effect of aging and diffuse chronic pancreatitis on pancreas elasticity evaluated using semiquantitative EUS elastography. Ultraschall Med. 2014;35:253–8.PubMedGoogle Scholar
  56. 56.
    Itoh Y, Itoh A, Kawashima H, et al. Quantitative analysis of diagnosing pancreatic fibrosis using EUS-elastography (comparison with surgical specimens). J Gastroenterol. 2014;49:1183–92.CrossRefPubMedGoogle Scholar
  57. 57.
    Dominguez-Muñoz JE, Iglesias-Garcia J, Castiñeira Alvariño M, et al. EUS elastography to predict pancreatic exocrine insufficiency in patients with chronic pancreatitis. Gastrointest Endosc. 2015;81:136–42.CrossRefPubMedGoogle Scholar
  58. 58.
    Imazu H, Mori N, Kanazawa K, et al. Contrast-enhanced harmonic endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening. Dig Dis Sci. 2014;59:1909–16.CrossRefPubMedGoogle Scholar
  59. 59.
    Choi JH, Seo DW, Choi JH, Park do H, Lee SS, Lee SK, Kim MH. Utility of contrast-enhanced harmonic EUS in the diagnosis of malignant gallbladder polyps (with videos). Gastrointest Endosc 2013; 78: 484–93Google Scholar
  60. 60.
    Park CH, Chung MJ, Oh TG, Park JY, Bang S, Park SW, Kim H, Hwang HK, Lee WJ, Song SY. Differential diagnosis between gallbladder adenomas and cholesterol polyps on contrast-enhanced harmonic endoscopic ultrasonography. Surg Endosc. 2013;27:1414–21.CrossRefPubMedGoogle Scholar
  61. 61.
    Rustemovic N, Cukovic-Cavka S, Opacic M, et al. Endoscopic ultrasound elastography as a method for screening the patients with suspected primary sclerosing cholangitis. Eur J Gastroenterol Hepatol. 2010;22:748–53.PubMedGoogle Scholar
  62. 62.
    Kannengiesser K, Mahlke R, Petersen F, et al. Contrast enhanced harmonic endoscopic ultrasound is able to discriminate benign submucosal lesions from gastrointestinal stromal tumors. Scand J Gastroenterol. 2012;47:1515–20.CrossRefPubMedGoogle Scholar
  63. 63.
    Sakamoto H, Kitano M, Matsui S, et al. Estimation of malignant potential of GIST by contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2011;73:27–237.Google Scholar
  64. 64.
    Yamashita Y, Kato J, Ueda K, et al. Contrast-enhanced endoscopic ultrasonography can predict a higher malignant potential of gastrointestinal stromal tumors by visualizing large newly formed vessels. J Clin Ultrasound. 2015;43:89–97.CrossRefPubMedGoogle Scholar
  65. 65.
    Gheorghe L, Gheorghe C, Cotruta B, Carabela A. CT aspects of gastrointestinal stromal tumors: adding EUS and EUS elastography to the diagnostic tools. J Gastrointestin Liver Dis. 2007;16:346–7.PubMedGoogle Scholar
  66. 66.
    Imazu H, Uchiyama Y, Matsunaga K, et al. Contrast-enhanced harmonic EUS with novel ultrasonographic contrast (Sonazoid) in the preoperative T-staging for pancreaticobiliary malignancies. Scand J Gastroenterol. 2010;45:732–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Kanamori A, Hirooka Y, Itoh A, et al. Usefulness of contrast enhanced endoscopic ultrasonography in the differentiation between malignant and benign lymphadenopathy. Am J Gastroenterol. 2006;101:45–51.CrossRefPubMedGoogle Scholar
  68. 68.
    Xia Y, Kitano M, Kudo M, et al. Characterization of intra-abdominal lesions of undetermined origin by contrast-enhanced harmonic EUS (with video). Gastrointest Endosc. 2010;72:637–42.CrossRefPubMedGoogle Scholar
  69. 69.
    Okasha HH, Mansour M, Attia KA, et al. Role of high resolution ultrasound/endosonography and elastography in predicting lymph node malignancy. Endosc Ultrasound. 2014;3:58–62.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Xu W, Shi J, Zeng X, et al. EUS elastography for the differentiation of benign and malignant lymph nodes: a meta-analysis. Gastrointest Endosc. 2011;74:1001–9.CrossRefPubMedGoogle Scholar
  71. 71.
    Knabe M, Günter E, Ell C, et al. Can EUS elastography improve lymph node staging in esophageal cancer? Surg Endosc. 2013;27:1196–202.CrossRefPubMedGoogle Scholar
  72. 72.
    Larsen MH, Fristrup C, Hansen TP, et al. Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard. Endoscopy. 2012;44:759–66.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Masayuki Kitano
    • 1
    Email author
  • Kosuke Minaga
    • 1
  • Masatoshi Kudo
    • 1
  1. 1.Department of Gastroenterology and HepatologyKinki University Faculty of MedicineOsaka-SayamaJapan

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