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Review of Ultrasound Enhancing Agents in Echocardiography for Better Diagnostic Accuracy

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Abstract

Purpose of Review

This abstract aims to examine the advancements in the utilization, indications, and implementation of ultrasound enhancing agents (UEAs) and their potential to enhance cost-effective diagnostics.

Recent Findings

The review highlights significant progress in the application of UEAs, particularly in improving the delineation of endocardial borders, enhancing interpretation of wall motion, and increasing diagnostic accuracy. Moreover, UEAs contribute to streamlining workflows and help avoid more expensive procedures, especially in cases with technically challenging or suboptimal studies.

Summary

UEAs have shown great promise in various medical scenarios, such as enhancing the visualization of the cardiac blood pool and enabling better assessment of ventricular borders, ventricular function, masses, and other intracavitary or myocardial abnormalities. This abstract presents an overview of the recent findings that underscore the potential benefits of UEAs in optimizing cardiac diagnostics while considering cost-effectiveness.

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Data Availability

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radio. 1968;3:356–66.

    Article  CAS  Google Scholar 

  2. Porter TR, Abdelmoneim S, Belcik JT, McCulloch ML, Mulvagh SL, Olson JJ, et al. Guidelines for the cardiac sonographer in the performance of contrast echocardiography: a focused update from the American Society of Echocardiography. J Am Soc Echocardiogr. 2014;27:797–810.

    Article  PubMed  Google Scholar 

  3. Wang S, et al. Targeting of microbubbles: contrast agents for ultrasound molecular imaging. J Drug Target. 2018;26(5–6):420–34.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zullino S, et al. From micro- to nano-multifunctional theranostic platform: effective ultrasound imaging is not just a matter of scale. Mol Imaging. 2018;17:1536012118778216.

    Article  PubMed  PubMed Central  Google Scholar 

  5. de Jong N, et al. Ultrasonic characterization of ultrasound contrast agents. Med Biol Eng Comput. 2009;47(8):861–73.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Omata D, et al. Lipid-based microbubbles and ultrasound for therapeutic application. Adv Drug Deliver Rev. 2020;154–155:236–44.

    Article  Google Scholar 

  7. Chitnis PV, Koppolu S, Mamou J, et al. Influence of shell properties on high-frequency ultrasound imaging and drug delivery using polymer-shelled microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control 2013; 60.

  8. Chitnis PV, Lee P, Mamou J, et al. Rupture threshold characterization of polymer-shelled ultrasound contrast agents subjected to static overpressure. J Appl Phys. 2011;109:84906–8490610.

    Article  PubMed  Google Scholar 

  9. Sirsi S, Borden M. Microbubble compositions, properties and biomedical applications. Bubble Sci Eng Technol. 2009;1(1–2):3–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Feinstein SB, et al. Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. J Am College Cardiologyvol. 1990;16(2):316–24.

    Article  CAS  Google Scholar 

  11. Mulvagh SL, et al. American Society of Echocardiography consensus statement on the clinical applications of ultrasonic contrast agents in echocardiography. J Am Soc Echocardiogr. 2008;21(11):1179–201 quiz 1281.

    Article  PubMed  Google Scholar 

  12. • Porter TR, Mulvagh SL, Abdelmoneim SS, Becher H, Belcik JT, Bierig M, et al. Clinical applications of ultrasonic enhancing agents in echocardiography: 2018 American Society of Echocardiography guidelines update. J Am Soc Echocardiogr. 2018;31:241–74.This paper updates the 2008 guidelines and replaces the term microbubbles with ultrasound enhancing agents. The paper also updates the new clinical evidence showing that UEAs are safe and efficacious for LV opacification in various clinical scenarios.

    Article  PubMed  Google Scholar 

  13. • Fraiche A, Strom J. Impact of ultrasound enhancing agents on clinical management. Curr Opin Cardiol. 2022;37(5):389–93.This paper updates the evidence that UEAs are cost effective in reducing downstream costs by improving endocardial border delineation. Improving workflows through enhanced reader confidence and study accuracy makes UEAs an asset in the echo lab despite its current laggard use.

    Article  PubMed  PubMed Central  Google Scholar 

  14. • Ellenberger, Katherine et al. “The effect of obesity on echocardiographic image quality.” Heart Lung Circ 2022; 31(2): 207–215.This paper demonstrates that increasing BMI, a surrogate for obesity, necessitates increasing UEA use to reduce nondiagnostic studies.

  15. Kooiman K, et al. Ultrasound-responsive cavitation nuclei for therapy and drug delivery. Ultrasound Med Biol. 2020;46(6):1296–325.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang M, et al. Sonoporation-induced cell membrane permeabilization and cytoskeleton disassembly at varied acoustic and microbubble-cell parameters. Sci Rep. 2018;8(1):3885.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  17. Hu Y, et al. Membrane perforation and recovery dynamics in microbubble-mediated sonoporation. Ultrasound Med Biol. 2013;39(12):2393–405.

    Article  PubMed  Google Scholar 

  18. Man VH, et al. Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation. J Phys Chem B. 2019;123(1):71–8.

    Article  CAS  PubMed  Google Scholar 

  19. Yong Y, Wu D, Fernandes V, Kopelen HA, Shimoni S, Nagueh SF, Callahan JD, Bruns DE, Shaw LJ, Quinones MA, Zoghbi WA. Diagnostic accuracy and cost-effectiveness of contrast echocardiography on evaluation of cardiac function in technically very difficult patients in the intensive care unit. Am J Cardiol. 2002;89(6):711–8.

    Article  PubMed  Google Scholar 

  20. Hughes RK, et al. Apical hypertrophic cardiomyopathy: the variant less known. J Am Heart Assoc. 2020;9(5):e015294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. • Nagueh, Sherif F et al. “Recommendations for multimodality cardiovascular imaging of patients with hypertrophic cardiomyopathy: an update from the American Society of Echocardiography, in Collaboration with the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography.” J Am Soc Echocardiogr 2022; 35(6): 533–569. This paper provides the latest ASE guidelines on how to image in HCM patients and excellent examples of multimodality imaging incorporating UEAs.

  22. Urbano-Moral JA, et al. Contrast-enhanced echocardiographic measurement of left ventricular wall thickness in hypertrophic cardiomyopathy: comparison with standard echocardiography and cardiac magnetic resonance. J Am Soc Echocardiogr. 2020;33(9):1106–15.

    Article  PubMed  Google Scholar 

  23. Phelan D, et al. Comparison of ventricular septal measurements in hypertrophic cardiomyopathy patients who underwent surgical myectomy using multimodality imaging and implications for diagnosis and management. Am J Cardiol. 2017;119(10):1656–62.

    Article  PubMed  Google Scholar 

  24. Lang RM, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Euro Heart J Cardiovasc Imaging. 2015;16(3):233–70.

    Article  Google Scholar 

  25. Aggarwal S, et al. Masking and unmasking of isolated noncompaction of the left ventricle with real-time contrast echocardiography. Circ Cardiovasc Imaging. 2017;10(11):e006999.

    Article  PubMed  Google Scholar 

  26. Gin KG, et al. Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale. J Am Coll Cardiol. 1993;22(7):1994–2000.

    Article  CAS  PubMed  Google Scholar 

  27. Goyal SK, Punnam SR, Verma G, Ruberg FL. Persistent left superior vena cava: a case report and review of literature. Cardiovasc Ultrasound. 2008;10(6):50.

    Article  Google Scholar 

  28. Bagur R, et al. A novel application of contrast echocardiography to exclude active coronary perforation bleeding in patients with pericardial effusion. Catheter Cardiovasc Interv: official journal of the Society for Cardiac Angiography & Interventions. 2013;82(2):221–9.

    Article  Google Scholar 

  29. Weinsaft JW, et al. Echocardiographic algorithm for post-myocardial infarction LV thrombus: a gatekeeper for thrombus evaluation by delayed enhancement CMR. JACC Cardiovasc imaging. 2016;9(5):505–15.

    Article  PubMed  Google Scholar 

  30. Camaj A, et al. Left ventricular thrombus following acute myocardial infarction: JACC state-of-the-art review. J Am College Cardiol. 2022;79(10):1010–22. https://doi.org/10.1016/j.jacc.2022.01.011.

    Article  Google Scholar 

  31. Janardhanan R, et al. Usefulness of myocardial contrast echocardiography using low-power continuous imaging early after acute myocardial infarction to predict late functional left ventricular recovery. Am J Cardiol. 2003;92(5):493–7.

    Article  PubMed  Google Scholar 

  32. Kurt M, et al. Impact of contrast echocardiography on evaluation of ventricular function and clinical management in a large prospective cohort. J Am College Cardiol. 2009;53(9):802–10.

    Article  Google Scholar 

  33. Senior R, et al. Clinical practice of contrast echocardiography: recommendation by the European Association of Cardiovascular Imaging (EACVI) 2017. Euro Heart J Cardiovasc Imaging. 2017;18(11):1205–1205af.

    Article  Google Scholar 

  34. Plana JC, Mikati IA, Dokainish H, et al. A randomized cross-over study for evaluation of the effect of image optimization with contrast on the diagnostic accuracy of dobutamine echocardiography in coronary artery disease: the OPTIMIZE trial. J Am Coll Cardiol Img. 2008;1:145.

    Article  Google Scholar 

  35. Woodward W, et al. Real-world performance and accuracy of stress echocardiography: the EVAREST observational multi-centre study. Euro Heart J Cardiovasc Imaging. 2022;23(5):689–98.

    Article  Google Scholar 

  36. Becher H, von Bibra H. “Verstärkung von Doppler-Signalen bei Aorten- und Mitralvitien” [Enhancement of Doppler signals in aortic and mitral valve diseases]. Zeitschrift fur Kardiologie. 1997;86(12):1033–9.

    Article  CAS  PubMed  Google Scholar 

  37. Smith LA, et al. Contrast agent increases Doppler velocities and improves reproducibility of aortic valve area measurements in patients with aortic stenosis. J Am Soc Echocardiogr. 2004;17(3):247–52.

    Article  PubMed  Google Scholar 

  38. Dwivedi G, Hickman M, Senior R. Accurate assessment of aortic stenosis with intravenous contrast. Eur J Echocardiogr. 2006;7(2):165–7.

    Article  PubMed  Google Scholar 

  39. Byrd BF 3rd, et al. Contrast echocardiography enhances tricuspid but not mitral regurgitation. Clin Cardiol. 1991;14(11 Suppl 5):V10–4.

    PubMed  Google Scholar 

  40. Sorrell, Vincent, Kumar, Sachin. "Doppler contrast echocardiography". Establishing better standards of care in doppler echocardiography, computed tomography and nuclear cardiology, edited by Richard Fleming, IntechOpen 2011; https://doi.org/10.5772/25152.

  41. Wei K, et al. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation. 1998;97(5):473–83.

    Article  CAS  PubMed  Google Scholar 

  42. Abdelmoneim SS, et al. Microvascular function in Takotsubo cardiomyopathy with contrast echocardiography: prospective evaluation and review of literature. J Am Soc Echocardiogr. 2009;22(11):1249–55.

    Article  PubMed  Google Scholar 

  43. Lashin H, et al. Contrast-enhanced echocardiography application in patients supported by extracorporeal membrane oxygenation (ECMO): a narrative review. J Cardiothorac Vasc Anesth. 2022;36(7):2080–9.

    Article  PubMed  Google Scholar 

  44. Pereira JB, et al. The feasibility of contrast echocardiography in the assessment of right ventricular size and function. Echocardiography. 2019;36(11):1979–88.

    Article  PubMed  Google Scholar 

  45. Argulian E, et al. Safety of ultrasonic enhancing agents in patients with COVID-19. J Am Soc Echocardiogr : official publication of the American Society of Echocardiography. 2020;33(7):906–8. https://doi.org/10.1016/j.echo.2020.04.022.

    Article  Google Scholar 

  46. Johri AM, et al. ASE statement on point-of-care ultrasound during the 2019 novel coronavirus pandemic. J Am Soc Echocardiogr. 2020;33(6):670–3.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Porter TR, Mulvagh SL, Abdelmoneim SS, Becher H, Belcik JT, Bierig M, et al. Clinical applications of ultrasonic enhancing agents in echocardiography: 2018 American Society of Echocardiography guidelines update. J Am Soc Echocardiogr. 2018;31:241–74.

    Article  PubMed  Google Scholar 

  48. Hoffmann R, et al. Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic resonance imaging, unenhanced and contrast-enhanced echocardiography. Euro Heart J. 2005;26(6):607–16.

    Article  Google Scholar 

  49. Lindner JR, Wei K. Contrast echocardiography. Curr Problems Cardiol. 2002;27(11):454–519.

    Article  Google Scholar 

  50. • Cosyns B, Helfen A, Leong-Poi H, Senior R. How to perform an ultrasound contrast myocardial perfusion examination? Euro Heart J Cardiovasc Imaging. 2022;23(6):727–9.This paper shows how to give UEAs step by step and tips and tricks on how to enhance the images.

    Article  Google Scholar 

  51. Gavan, Kane [@gavankane] “Really useful echo contrast (UEA) trouble shooting tips by @ceb_cardsdoc at #MayoEchoBR @JaeKOh2 @MayoClinicCV” Twitter, April 24,2021. https://twitter.com/garvankane/status/1385986960087470080

  52. D’Amico A, et al. Definity, an affinity for painful crisis: a case series describing vaso-occlusive pain crises in sickle cell patients undergoing echocardiogram with Definity contrast. Euro Heart J Case Rep. 2020;5(2):ytaa555.

    Article  Google Scholar 

  53. Lindner JR, et al. Expert consensus statement from the American Society of Echocardiography on hypersensitivity reactions to ultrasound enhancing agents in patients with allergy to polyethylene glycol. J Am Soc Echocardiogr. 2021;34(7):707–8.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Desai AK, et al. Hypersensitivity cross-reactivity for ultrasound-enhancing agents and COVID-19 vaccines. J Am Soc Echocardiogr. 2022;35(5):523–5.

    Article  PubMed  PubMed Central  Google Scholar 

  55. • Lindner JR. Contrast echocardiography: current status and future directions. Heart (British Cardiac Society). 2021;107(1):18–24.This paper reviews the latest clinical indications, current and emerging, for UEAs.

    PubMed  Google Scholar 

  56. Kopechek JA, McTiernan CF, Chen X, et al. Ultrasound and microbubble-targeted delivery of a microRNA inhibitor to the heart suppresses cardiac hypertrophy and preserves cardiac function. Theranostics. 2019;9:7088–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pacella JJ, Brands J, Schnatz FG, Black JJ, Chen X, Villanueva FS. Treatment of microvascular micro-embolization using microbubbles and long-tone-burst ultrasound: an in vivo study. Ultrasound Med Biol. 2015;41:456–64.

    Article  PubMed  Google Scholar 

  58. Roos ST, Juffermans LJM, Slikkerveer J, Unger EC, Porter TR, Kamp O. Sonothrombolysis in acute stroke and myocardial infarction: a systematic review. IJC Heart Vess. 2014;4:1–6.

    Article  Google Scholar 

  59. • Mathias W., Tsutsui J.M., Tavares B.G., et al."Sonothrombolysis in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention". J Am Coll Cardiol 2019;73:2832–2842.This paper shows the first cardiology benefit of UEAs in myocardial infarction.

  60. Mason OR, Davidson BP, Sheeran P, et al. Augmentation of tissue perfusion in patients with peripheral artery disease using microbubble cavitation. J Am Coll Cardiol Img. 2020;13:641–51.

    Article  Google Scholar 

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Authors and Affiliations

  1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Ritu Thamman

  2. Division of Cardiology, Sarver Heart Center, University of Arizona, Tucson, USA

    Rajesh Janardhanan

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  1. Ritu Thamman
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R.T. and R.J. wrote the main manuscript text and prepared the figures. All authors reviewed the manuscript.

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Correspondence to Ritu Thamman.

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Thamman, R., Janardhanan, R. Review of Ultrasound Enhancing Agents in Echocardiography for Better Diagnostic Accuracy. Curr Cardiovasc Imaging Rep 17, 33–42 (2024). https://doi.org/10.1007/s12410-024-09589-5

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