Contrast-Enhanced Ultrasonography: Clinical Applications

  • Julian KüstermeyerEmail author


Contrast-enhanced ultrasound (CEUS) is an emerging diagnostic technique that combines the use of a contrast agent with established ultrasound techniques. CEUS allows analysis of perfusion patterns in greater detail than conventional sonographic modalities. Though most applications in the head and neck remain off-label, many studies report an improvement of diagnostic accuracy by using CEUS in the head and neck, and there appear to be a variety of promising applications for future clinical routines.


Contrast-enhanced Contrast agent CEUS Salivary glands Lymph nodes Time-intensity curve Paraganglioma Tumor monitoring Thyroid gland 

Supplementary material

Video 16.1

Pleomorphic adenoma (MP4 20782 kb)

Video 16.2

Warthin’s tumor (MP4 24857 kb)

Video 16.3

Reactive lymph node (MP4 23120 kb)

Video 16.4

Carcinoma metastasis (MP4 31294 kb)

Video 16.5

Paraganglioma (MP4 15637 kb)

Video 16.6

Thyroid nodules (MP4 21089 kb)


  1. 1.
    Chung YE, Kim KW. Contrast-enhanced ultrasonography: advance and current status in abdominal imaging. Ultrasonography. 2014;34:3–18.CrossRefGoogle Scholar
  2. 2.
    Claudon M, Dietrich C, Choi B, Cosgrove D, Kudo M, Nolsøe C, et al. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012. Ultraschall Med. 2013;34:11–29.CrossRefGoogle Scholar
  3. 3.
    Nolsøe CP, Lorentzen T. International guidelines for contrast-enhanced ultrasonography: ultrasound imaging in the new millennium. Ultrasonography. 2016;35:89–103.CrossRefGoogle Scholar
  4. 4.
    Piscaglia F, Nolsøe C, Dietrich C, Cosgrove D, Gilja O, Bachmann Nielsen M, et al. The EFSUMB guidelines and recommendations on the clinical practice of Contrast Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications. Ultraschall Med. 2012;33:33–59.CrossRefGoogle Scholar
  5. 5.
    Meltzer RS. Food and Drug Administration ultrasound device regulation: the output display standard, the “mechanical index,” and ultrasound safety. J Am Soc Echocardiogr. 1996;9:216–20.CrossRefGoogle Scholar
  6. 6.
    von Herbay A, Haeussinger D, Gregor M, Vogt C. Characterization and detection of hepatocellular carcinoma (HCC): comparison of the ultrasound contrast agents SonoVue (BR 1) and Levovist (SH U 508A). Ultraschall Med. 2007;28:168–75.CrossRefGoogle Scholar
  7. 7.
    Blomley MJK, Cooke JC, Unger EC, Monaghan MJ, Cosgrove DO. Science, medicine, and the future: Microbubble contrast agents: a new era in ultrasound. BMJ. 2001;322:1222.CrossRefGoogle Scholar
  8. 8.
    Burns PN. Basics. In: Weskott H-P, editor. Contrast-enhanced ultrasound. 2nd ed. Bremen: UNI-MED; 2013. p. 16–24.Google Scholar
  9. 9.
    Lindner JR. Microbubbles in medical imaging: current applications and future directions. Nat Rev Drug Discov. 2004;3:527–33.CrossRefGoogle Scholar
  10. 10.
    Qin S, Caskey CF, Ferrara KW. Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering. Phys Med Biol. 2009;54:R27–57.CrossRefGoogle Scholar
  11. 11.
    Postema M, Gilja OH. Contrast-enhanced and targeted ultrasound. World J Gastroenterol. 2011;17:28–41.CrossRefGoogle Scholar
  12. 12.
    Ignee A, Atkinson NSS, Schuessler G, Dietrich CF. Ultrasound contrast agents. Endosc Ultrasound. 2016;5:355–62.CrossRefGoogle Scholar
  13. 13.
    Solivetti FM, Elia F, Musicco F, Bonagura AC, Di Leo N, Iera J, et al. Anaphylactic shock induced by sulphur hexafluoride in an individual with no history of heart disease: case report and literature review. Ultraschall Med. 2012;33:597–8.CrossRefGoogle Scholar
  14. 14.
    Torres A, Koskinen SK, Gjertsen H, Fischler B. Contrast-enhanced ultrasound using sulfur hexafluoride is safe in the pediatric setting. Acta Radiol. 2017;58:1395–9.CrossRefGoogle Scholar
  15. 15.
    Torzilli G. Adverse effects associated with SonoVue® use. Expert Opin Drug Saf. 2005;4:399–401.CrossRefGoogle Scholar
  16. 16.
    Tang C, Fang K, Guo Y, Li R, Fan X, Chen P, et al. Safety of sulfur hexafluoride microbubbles in sonography of abdominal and superficial organs: retrospective analysis of 30,222 cases. J Ultrasound Med. 2017;36:531–8.CrossRefGoogle Scholar
  17. 17.
    Appis AW, Tracy MJ, Feinstein SB. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications. Echo Res Pract. 2015;2:R55–62.CrossRefGoogle Scholar
  18. 18.
    Dumitriu D, Dudea SM, Botar-Jid C, Baciut G. Ultrasonographic and sonoelastographic features of pleomorphic adenomas of the salivary glands. Med Ultrason. 2010;12:175–83.PubMedGoogle Scholar
  19. 19.
    Pinkston J, Cole P. Incidence rates of salivary gland tumors: results from a population-based study. Otolaryngol Head Neck Surg. 1999;120:834–40.CrossRefGoogle Scholar
  20. 20.
    David E, Cantisani V, De Vincentiis M, Sidhu PS, Greco A, Tombolini M, et al. Contrast-enhanced ultrasound in the evaluation of parotid gland lesions: an update of the literature. Ultrasound. 2016;24:104–10.CrossRefGoogle Scholar
  21. 21.
    Gou JM, Chen Q, Zhou Q, Liu YX. Quantitative diagnosis of salivary gland tumors with contrast-enhanced ultrasound--a preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:784–90.CrossRefGoogle Scholar
  22. 22.
    Küstermeyer J, Klingelhöfer G, Welkoborsky H-J. [Analysis of perfusion parameters within salivary gland tumors using contrast enhanced ultrasound]. [Article in German]. Laryngorhinootologie. 2016;95:688–93.CrossRefGoogle Scholar
  23. 23.
    Knopf A, Mansour N, Chaker A, Bas M, Stock K. Multimodal ultrasonographic characterisation of parotid gland lesions--a pilot study. Eur J Radiol. 2012;81:3300–5.CrossRefGoogle Scholar
  24. 24.
    Fischer T, Paschen C, Slowinski T, Alkhameri A, Berl J, Klingebiel R, et al. Differentiation of parotid gland tumors with contrast-enhanced ultrasound. Fortschr Röntgenstr. 2009;182:155–62.CrossRefGoogle Scholar
  25. 25.
    Pinkston JA, Cole P. Cigarette smoking and Warthin’s tumor. Am J Epidemiol. 1996;144:183–7.CrossRefGoogle Scholar
  26. 26.
    Zengel P, Berghaus A, Weiler C, Reiser M, Clevert DA. Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for evaluating obstructive disease and secretory dysfunction of the salivary glands. Eur Radiol. 2011;21:1339–48.CrossRefGoogle Scholar
  27. 27.
    Siedek V, Rytvina M, Klotz LV, Berghaus A, Clevert D-A, Strieth S. Validation of contrast-enhanced ultrasound-derived intensity-time gradients in submandibular gland sialolithotomy patients. Eur Arch Otorhinolaryngol. 2013;270:1941–6.CrossRefGoogle Scholar
  28. 28.
    Wei X, Li Y, Zhang S, Li X, Wang H, Yong X, et al. Evaluation of microvascularization in focal salivary gland lesions by contrast-enhanced ultrasonography (CEUS) and Color Doppler sonography. Clin Hemorheol Microcirc. 2013;54:259–71.PubMedGoogle Scholar
  29. 29.
    Klotz LV, Ingrisch M, Eichhorn ME, Niemoeller O, Siedek V, Gürkov R, et al. Monitoring parotid gland tumors with a new perfusion software for contrast-enhanced ultrasound. Clin Hemorheol Microcirc. 2014;58:261–9.PubMedGoogle Scholar
  30. 30.
    Badea AF, Bran S, Tamas-Szora A, Floareş A, Badea R, Baciut G. Solid parotid tumors: an individual and integrative analysis of various ultrasonographic criteria. A prospective and observational study. Med Ultrason. 2013;15:289–98.CrossRefGoogle Scholar
  31. 31.
    Moritz JD, Ludwig A, Oestmann J-W. Contrast-enhanced color doppler sonography for evaluation of enlarged cervical lymph nodes in head and neck tumors. Am J Roentgenol. 2000;174:1279–84.CrossRefGoogle Scholar
  32. 32.
    Schade G. [Experiences with using the ultrasound contrast medium Levovist in differentiation of cervical lymphomas with color-coded duplex ultrasound]. [Article in German]. Laryngorhinootologie. 2001;80:209–13.CrossRefGoogle Scholar
  33. 33.
    Jecker P, Engelke JC, Westhofen M. [Possible application of a signal enhancer for duplex ultrasound in otorhinolaryngology]. [Article in German]. Laryngorhinootologie. 2008;77:289–93.CrossRefGoogle Scholar
  34. 34.
    Dudea SM, Lenghel M, Botar-Jid C, Vasilescu D, Duma M. Ultrasonography of superficial lymph nodes: benign vs. malignant. Med Ultrason. 2012;14:294–306.PubMedGoogle Scholar
  35. 35.
    Zenk J, Bozzato A, Steinhart H, Greess H, Iro H. Metastatic and inflammatory cervical lymph nodes as analyzed by contrast-enhanced color-coded Doppler ultrasonography: quantitative dynamic perfusion patterns and histopathologic correlation. Ann Otol Rhinol Laryngol. 2005;114:43–7.CrossRefGoogle Scholar
  36. 36.
    Schulte-Altedorneburg G, Demharter J, Linné R, Droste DW, Bohndorf K, Bücklein W. Does ultrasound contrast agent improve the diagnostic value of colour and power Doppler sonography in superficial lymph node enlargement? Eur J Radiol. 2003;48:252–7.CrossRefGoogle Scholar
  37. 37.
    Schröder RJ, Mäurer J, Hidajat N, Willam C, Hell B, Weber S, et al. [Signal-enhanced color-coded duplex sonography of reactively and metastatically enlarged lymph nodes]. [Article in German]. Rofo. 1998;168:57–63.CrossRefGoogle Scholar
  38. 38.
    Rubaltelli L, Khadivi Y, Tregnaghi A, Stramare R, Ferro F, Borsato S, et al. Evaluation of lymph node perfusion using continuous mode harmonic ultrasonography with a second-generation contrast agent. J Ultrasound Med. 2004;23:829–36.CrossRefGoogle Scholar
  39. 39.
    Yu M, Liu Q, Song HP, Han ZH, Su HL, He GB, et al. Clinical application of contrast-enhanced ultrasonography in diagnosis of superficial lymphadenopathy. J Ultrasound Med. 2010;29:735–40.CrossRefGoogle Scholar
  40. 40.
    Dudau C, Hameed S, Gibson D, Muthu S, Sandison A, Eckersley RJ, et al. Can contrast-enhanced ultrasound distinguish malignant from reactive lymph nodes in patients with head and neck cancers? Ultrasound Med Biol. 2014;40:747–54.CrossRefGoogle Scholar
  41. 41.
    Weskott H-P. Ultrasound in the diagnostic management of malignant lymphomas. Radiologe. 2012;52:347–59.CrossRefGoogle Scholar
  42. 42.
    Nakase K, Yamamoto K, Hiasa A, Tawara I, Yamaguchi M, Shiku H. Contrast-enhanced ultrasound examination of lymph nodes in different types of lymphoma. Cancer Detect Prev. 2006;30:188–91.CrossRefGoogle Scholar
  43. 43.
    Rübenthaler J, Lutz J, Reiser M, Clevert DA. [Paraganglioma of the head and neck: follow-up of interventional procedures with CEUS]. [Article in German]. Ultraschall Med. 2015;36:541–3.CrossRefGoogle Scholar
  44. 44.
    Küstermeyer J, Deichmüller CC, Albers M, Graß SK, Welkoborsky HJ. Quantifizierung des präoperativen Embolisationseffektes bei Glomus caroticum Tumoren durch kontrastverstärkte Sonographie. [Abstract.] 88th Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery; 2017.
  45. 45.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1–133.CrossRefGoogle Scholar
  46. 46.
    Nemec U, Nemec SF, Novotny C, Weber M, Czerny C, Krestan CR. Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy. Eur Radiol. 2012;22:1357–65.CrossRefGoogle Scholar
  47. 47.
    Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L, et al. American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi Medical Guidelines for clinical practice for the diagnosis and management of thyroid nodules--2016 update. Endocr Pract. 2016;22:622–39.CrossRefGoogle Scholar
  48. 48.
    Argalia G, De Bernardis S, Mariani D, Abbattista T, Taccaliti A, Ricciardelli L, et al. Ultrasonographic contrast agent: evaluation of time-intensity curves in the characterisation of solitary thyroid nodules. Radiol Med. 2002;103:407–13.PubMedGoogle Scholar
  49. 49.
    Bartolotta TV, Midiri M, Galia M, Runza G, Attard M, Savoia G, et al. Qualitative and quantitative evaluation of solitary thyroid nodules with contrast-enhanced ultrasound: initial results. Eur Radiol. 2006;16:2234–41.CrossRefGoogle Scholar
  50. 50.
    Spiezia S, Farina R, Cerbone G, Assanti AP, Iovino V, Siciliani M, et al. Analysis of color Doppler signal intensity variation after Levovist injection: a new approach to the diagnosis of thyroid nodules. J Ultrasound Med. 2001;20:223–31.CrossRefGoogle Scholar
  51. 51.
    Jin L, Xu C, Xie X, Li F, Lv X, Du L. An algorithm of image heterogeneity with contrast-enhanced ultrasound in differential diagnosis of solid thyroid nodules. Ultrasound Med Biol. 2017;43:104–10.CrossRefGoogle Scholar
  52. 52.
    Cantisani V, Consorti F, Guerrisi A, Guerrisi I, Ricci P, Di Segni M, et al. Prospective comparative evaluation of quantitative-elastosonography (Q-elastography) and contrast-enhanced ultrasound for the evaluation of thyroid nodules: preliminary experience. Eur J Radiol. 2013;82:1892–8.CrossRefGoogle Scholar
  53. 53.
    Friedrich-Rust M, Sperber A, Holzer K, Diener J, Grünwald F, Badenhoop K, et al. Real-time elastography and contrast-enhanced ultrasound for the assessment of thyroid nodules. Exp Clin Endocrinol Diabetes. 2010;118:602–9.CrossRefGoogle Scholar
  54. 54.
    Jiang J, Shang X, Zhang H, Ma W, Xu Y, Zhou Q, et al. Correlation between maximum intensity and microvessel density for differentiation of malignant from benign thyroid nodules on contrast-enhanced sonography. J Ultrasound Med. 2014;33:1257–63.CrossRefGoogle Scholar
  55. 55.
    Molinari F, Mantovani A, Deandrea M, Limone P, Garberoglio R, Suri JS. Characterization of single thyroid nodules by contrast-enhanced 3-d ultrasound. Ultrasound Med Biol. 2010;36:1616–25.CrossRefGoogle Scholar
  56. 56.
    Zhang Y, Luo Y-K, Zhang M-B, Li J, Li J, Tang J. Diagnostic accuracy of contrast-enhanced ultrasound enhancement patterns for thyroid nodules. Med Sci Monit. 2016;22:4755–64.CrossRefGoogle Scholar
  57. 57.
    Li F, Wang Y, Bai B, Wang S, Liu S. Advantages of routine ultrasound combined with contrast-enhanced ultrasound in diagnosing papillary thyroid carcinoma. Ultrasound Q. 2017;33:213–8.CrossRefGoogle Scholar
  58. 58.
    Zhou X, Zhou P, Hu Z, Tian SM, Zhao Y, Liu W, et al. Diagnostic efficiency of quantitative contrast-enhanced ultrasound indicators for discriminating benign from malignant solid thyroid nodules. J Ultrasound Med. 2017;22:4755.Google Scholar
  59. 59.
    Ma J-J, Ding H, Xu B-H, Xu C, Song L-J, Huang B-J, et al. Diagnostic performances of various gray-scale, color Doppler, and contrast-enhanced ultrasonography findings in predicting malignant thyroid nodules. Thyroid. 2014;24:355–63.CrossRefGoogle Scholar
  60. 60.
    Schleder S, Janke M, Agha A, Schacherer D, Hornung M, Schlitt HJ, et al. Preoperative differentiation of thyroid adenomas and thyroid carcinomas using high resolution contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc. 2015;61:13–22.CrossRefGoogle Scholar
  61. 61.
    Williams R, Hudson JM, Lloyd BA, Sureshkumar AR, Lueck G, Milot L, et al. Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy. Radiology. 2011;260:581–90.CrossRefGoogle Scholar
  62. 62.
    Lassau N, Lamuraglia M, Vanel D, Le Cesne A, Chami L, Jaziri S, et al. Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases. Ann Oncol. 2005;16:1054–60.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology, Head and Neck SurgeryKRH Nordstadt Clinic–Academic HospitalHannoverGermany

Personalised recommendations