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Contrast echocardiography: Contrast agents, safety, and imaging technique

Hanna Ahmed, MD
Section Editor
Warren J Manning, MD
Deputy Editor
Brian C Downey, MD, FACC


Contrast echocardiography is a technique for improving echocardiographic resolution and providing real time assessment of intracardiac blood flow. Agitated saline contrast provides contrast in the right heart and enables detection of right to left shunts. Opacification of the left ventricular (LV) cavity by contrast agents developed to traverse the pulmonary vasculature permits improved endocardial border detection [1]. Contrast echocardiography can also enhance delineation of Doppler signal [1]. Additional uses of contrast echocardiography are to assess myocardial perfusion [2] and viability [3].

The development and safety of microbubbles for echocardiographic contrast and the optimization of the echocardiographic settings for visualizing contrast will be reviewed here. The current and potential clinical applications of CE are discussed separately. (See "Contrast echocardiography: Clinical applications".)


Mechanism of contrast — As sound travels from one medium to another, the change in density (known as acoustic impedance) at the interface causes the reflection of sound waves [4]. The greater the difference in the media densities, the more echogenic the interface. Gas is an excellent contrast agent since it is 100,000 times less dense than blood.

Agitated saline contrast — Agitated saline solution administered via intravenous injection provides air microbubble contrast in the right heart. The air microbubbles are short-lived and diffuse into the lungs when traversing the pulmonary circulation. Therefore the microbubbles enter the left heart only in the presence of a right to left intracardiac or extracardiac (pulmonary arteriovenous) shunt. Saline microbubbles are therefore helpful in examining the right heart and identifying shunts. (See "Contrast echocardiography: Clinical applications", section on 'Clinical applications for agitated saline contrast' and "Patent foramen ovale", section on 'Ultrasound techniques'.)

Transpulmonary passage of contrast agents — To allow left heart evaluation, an ideal contrast microbubble must be small and durable enough to traverse the pulmonary circulation to pass into the left heart from an intravenous injection. Improvements in contrast agents have resulted from the exploitation of knowledge concerning both the mechanisms of echogenicity and the impediments to transpulmonary passage.

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Literature review current through: Nov 2017. | This topic last updated: Aug 25, 2017.
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  1. Mulvagh SL, Rakowski H, Vannan MA, et al. American Society of Echocardiography Consensus Statement on the Clinical Applications of Ultrasonic Contrast Agents in Echocardiography. J Am Soc Echocardiogr 2008; 21:1179.
  2. Porter TR, Li S, Kricsfeld D, Armbruster RW. Detection of myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles using transient response second harmonic imaging. J Am Coll Cardiol 1997; 29:791.
  3. Rovai D, Zanchi M, Lombardi M, et al. Residual myocardial perfusion in reversibly damaged myocardium by dipyridamole contrast echocardiography. Eur Heart J 1996; 17:296.
  4. Feigenbaum H. Instrumentation. In: Echocardiography, Feigenbaum H (Ed), Lea and Febiger, Philadelphia 1981. p.3.
  5. Berwing K, Schlepper M, Bahavar H, Buchwald A. Significance and selection of contrast solution for myocardial contrast echocardiography. In: Myocardial Contrast Two-Dimensional Echocardiography, Meerbaum S, Meltzer R (Eds), Kluwer Academic Publishers, Boston 1989. p.63.
  6. Meerbaum S. Development and validation of MC-2DE methodology. In: Myocardial Contrast Two-Dimensional Echocardiography, Meerbaum S, Meltzer R (Eds), Kluwer Academic Publishers, Boston 1989. p.24.
  7. Edelman S. Understanding Ultrasound Physics, 4th ed, E.S.P. Ultrasound, Woodlands, TX 2012.
  8. Kates MA, Meza MF, Barbee RW, et al. Potential clinical implications of abnormal myocardial perfusion patterns immediately after reperfusion in a canine model: a myocardial contrast echocardiography study. Am Heart J 1996; 132:303.
  9. Ito H, Tomooka T, Sakai N, et al. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992; 85:1699.
  10. Sabia PJ, Powers ER, Ragosta M, et al. An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. N Engl J Med 1992; 327:1825.
  11. Meerbaum S. Introduction and general background. In: Myocardial Contrast Two-Dimensional Echocardiography, Meerbaum S, Meltzer R (Eds), Kluwer Academic Publishers, Boston 1989. p.3.
  12. Feinstein SB, Cheirif J, Ten Cate FJ, et al. Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. J Am Coll Cardiol 1990; 16:316.
  13. Kaul S. Myocardial contrast echocardiography: 15 years of research and development. Circulation 1997; 96:3745.
  14. Meza M, Greener Y, Hunt R, et al. Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent. Am Heart J 1996; 132:871.
  15. Cohen JL, Cheirif J, Segar DS, et al. Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. J Am Coll Cardiol 1998; 32:746.
  16. Kitzman DW, Goldman ME, Gillam LD, et al. Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images. Am J Cardiol 2000; 86:669.
  17. Romero JR, Frey JL, Schwamm LH, et al. Cerebral ischemic events associated with 'bubble study' for identification of right to left shunts. Stroke 2009; 40:2343.
  18. Herzog CA. Incidence of adverse events associated with use of perflutren contrast agents for echocardiography. JAMA 2008; 299:2023.
  19. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology 2005; 216:106.
  20. Main ML, Goldman JH, Grayburn PA. Thinking outside the "box"-the ultrasound contrast controversy. J Am Coll Cardiol 2007; 50:2434.
  21. Douglas, PS, Weyman, et al. ontrast echocardiography: Past, present and...future? J Am Coll Cardiol Img 2008; 1:107.
  22. Dolan MS, Gala SS, Dodla S, et al. Safety and efficacy of commercially available ultrasound contrast agents for rest and stress echocardiography a multicenter experience. J Am Coll Cardiol 2009; 53:32.
  23. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125574.htm (Accessed on March 07, 2014).
  24. Exuzides A, Main ML, Colby C, et al. A retrospective comparison of mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent. JACC Cardiovasc Imaging 2010; 3:578.
  25. Weiss RJ, Ahmad M, Villanueva F, et al. CaRES (Contrast Echocardiography Registry for Safety Surveillance): a prospective multicenter study to evaluate the safety of the ultrasound contrast agent definity in clinical practice. J Am Soc Echocardiogr 2012; 25:790.
  26. Main ML, Hibberd MG, Ryan A, et al. Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent. JACC Cardiovasc Imaging 2014; 7:40.
  27. Wei K, Shah S, Jaber WA, DeMaria A. An observational study of the occurrence of serious adverse reactions among patients who receive optison in routine medical practice. J Am Soc Echocardiogr 2014; 27:1006.
  28. Wei K, Main ML, Lang RM, et al. The effect of Definity on systemic and pulmonary hemodynamics in patients. J Am Soc Echocardiogr 2012; 25:584.
  29. Main ML, Grayburn PA, Lang RM, et al. Effect of Optison on pulmonary artery systolic pressure and pulmonary vascular resistance. Am J Cardiol 2013; 112:1657.
  30. Muskula PR, Main ML. Safety With Echocardiographic Contrast Agents. Circ Cardiovasc Imaging 2017; 10.
  31. Fine NM, Abdelmoneim SS, Dichak A, et al. Safety and feasibility of contrast echocardiography for LVAD evaluation. JACC Cardiovasc Imaging 2014; 7:429.
  32. Bennett CE, Tweet MS, Michelena HI, et al. Safety and Feasibility of Contrast Echocardiography for ECMO Evaluation. JACC Cardiovasc Imaging 2017; 10:603.
  33. Grecu L, Fishman MA. Beware of life-threatening activation of air bubble detector during contrast echocardiography in patients on venoarterial extracorporeal membrane oxygenator support. J Am Soc Echocardiogr 2014; 27:1130.
  34. Kutty S, Xiao Y, Olson J, et al. Safety and Efficacy of Cardiac Ultrasound Contrast in Children and Adolescents for Resting and Stress Echocardiography. J Am Soc Echocardiogr 2016; 29:655.
  35. McMahon CJ, Ayres NA, Bezold LI, et al. Safety and efficacy of intravenous contrast imaging in pediatric echocardiography. Pediatr Cardiol 2005; 26:413.
  36. Lindner JR, Firschke C, Wei K, et al. Myocardial perfusion characteristics and hemodynamic profile of MRX-115, a venous echocardiographic contrast agent, during acute myocardial infarction. J Am Soc Echocardiogr 1998; 11:36.
  37. Lindner JR, Dent JM, Moos SP, et al. Enhancement of left ventricular cavity opacification by harmonic imaging after venous injection of Albunex. Am J Cardiol 1997; 79:1657.
  38. Kaul S. New developments in ultrasound systems for contrast echocardiography. Clin Cardiol 1997; 20:I27.
  39. Colon PJ 3rd, Richards DR, Moreno CA, et al. Benefits of reducing the cardiac cycle-triggering frequency of ultrasound imaging to increase myocardial opacification with FSO69 during fundamental and second harmonic imaging. J Am Soc Echocardiogr 1997; 10:602.
  40. Nahar T, Croft L, Shapiro R, et al. Comparison of four echocardiographic techniques for measuring left ventricular ejection fraction. Am J Cardiol 2000; 86:1358.
  41. Wei K, Skyba DM, Firschke C, et al. Interactions between microbubbles and ultrasound: in vitro and in vivo observations. J Am Coll Cardiol 1997; 29:1081.
  42. Firschke C, Lindner JR, Wei K, et al. Myocardial perfusion imaging in the setting of coronary artery stenosis and acute myocardial infarction using venous injection of a second-generation echocardiographic contrast agent. Circulation 1997; 96:959.
  43. Ohmori K, Cotter B, Kwan OL, et al. Relation of contrast echo intensity and flow velocity to the amplification of contrast opacification produced by intermittent ultrasound transmission. Am Heart J 1997; 134:1066.
  44. Porter TR, Kricsfeld A, Deligonul U, Xie F. Detection of regional perfusion abnormalities during adenosine stress echocardiography with intravenous perfluorocarbon-exposed sonicated dextrose albumin. Am Heart J 1996; 132:41.
  45. Ismail S, Jayaweera AR, Goodman NC, et al. Detection of coronary stenoses and quantification of the degree and spatial extent of blood flow mismatch during coronary hyperemia with myocardial contrast echocardiography. Circulation 1995; 91:821.
  46. Sutherland GR, Stewart MJ, Groundstroem KW, et al. Color Doppler myocardial imaging: a new technique for the assessment of myocardial function. J Am Soc Echocardiogr 1994; 7:441.
  47. Tuchnitz A, von Bibra H, Sutherland GR, et al. Doppler energy: a new acquisition technique for the transthoracic detection of myocardial perfusion defects with the use of a venous contrast agent. J Am Soc Echocardiogr 1997; 10:881.
  48. Venkatraman S, Rao NA. Combining pulse compression and adaptive drive signal design to inverse filter the transducer system response and improve resolution in medical ultrasound. Med Biol Eng Comput 1996; 34:318.
  49. Albrecht T, Urbank A, Mahler M, et al. Prolongation and optimization of Doppler enhancement with a microbubble US contrast agent by using continuous infusion: preliminary experience. Radiology 1998; 207:339.
  50. Weissman NJ, Cohen MC, Hack TC, et al. Infusion versus bolus contrast echocardiography: a multicenter, open-label, crossover trial. Am Heart J 2000; 139:399.