One of the most recent revolutions of echocardiography has been the introduction of intravenous contrast agents for the optimization of echocardiographic imaging. This has proven to be of tremendous value, over and above the parallel improvement of equipment manufactured and new transducers capable of transmitting and receiving ultrasound at different frequencies. There are now clear recommendations by the American Society of Echocardiography jointly with the Europeans that regular use of intravenous contrast agents in echocardiography benefits image interpretation at rest and perhaps even more, during stress [1,2]

Nihoyannopoulos, Petros

Hospital Chronicles (E-Journal)

62HOSPITAL CHRONICLES, SUPPLEMENT 2006 CLINICAL APPLICATIONS OF CONTRAST ECHOCARDIOGRAPHY63Clinical Applications of Contrast EchocardiographyPetros Nihoyannopoulos, MDOne of the most recent revolutions of echocardiography has been the introduction of intravenous contrast agents for the optimization of echocardiographic imaging. This has proven to be of tremendous value, over and above the parallel improvement of equipment manufactured and new transducers capable of transmitting and receiving ultrasound at different frequencies. There are now clear recommendations by the American Society of Echocardiography jointly with the Europeans that regular use of intravenous contrast agents in echocardiography benefits image interpretation at rest and perhaps even more, during stress [1,2].The symposium held during the Euroecho 8 congress in Athens, December 2004 on “Clinical value and perspectives of Contrast Echocardiography” gives us the op-portunity to highlight the most important clinical implementations but also research opportunities ready to be implemented in clinical echocardiography today.There are now a number of second generation echo-contrast agents that have been in the market for several years all over the world and there are more to come very soon in the market, demonstrating the benefit of those agents. In the United States, Optison and Definity are routinely used to improve image quality. In Europe, Optison and Sonovue are used for the same indications. Several hundreds of thousands of patients have received echo-contrast todate and compared to other contrast agents used in imaging, echo contrast agents are the safest [3]. During that symposium, experts from all-over Europe presented their experience in considering current but also some future applications of contrast echocardiography. These new possibilities are clearly illustrated in the articles of this supplement from which some important remarks can be drawn.Image quality is crucial to formulate a diagnosis. Even experts can produce poor images and need to use contrast to improve quality. This is particularly important when other non-experts in echocardiography are looking at the pictures in order to make a clinical decision and if image quality is not convincing, then they will turn into alternative imaging modalities that may produce a better picture. One good picture is worth a thousand words! Using contrast echocardiography and thus improving endocardial delineation of the left ventricle, allows for a better and more reproducible assessment of left ventricu-lar ejection fraction in such a way that is comparable to cardiac magnetic resonance imaging (CMR) with only a fraction of its cost. This has been elegantly demonstrated by Hoffmann et al who used Sonovue in 120 patients from several centers in order to determine the agreement of unenhanced and contrast-enhanced echocardiography against biplane cine-ventriculography and CMR [4]. They convincingly showed that contrast-enhanced echocardiography significantly improves inter-observer variability for the assessment of ejection fraction to a level obtained by CMR, while cine-ven-triculography exhibits a large inter-observer variability [4]. Furthermore, assessing re-CARDIOLOGY UPDATE 2006Reader & Consultant Cardiologist, Hammersmith Hospital, NHLI, Imperial College London, e-mail: p.nihoyannopoulos@imperial.ac.ukHOSPITAL CHRONICLES 2006, SUPPLEMENT: 62–64Address for correspondence:Petros Nihoyannopoulose-mail: p.nihoyannopoulos@imperial.ac.uk62HOSPITAL CHRONICLES, SUPPLEMENT 2006 CLINICAL APPLICATIONS OF CONTRAST ECHOCARDIOGRAPHY63gional ventricular function is crucial when assessing coronary artery disease patients. In this symposium, Dr Roxy Senior outlined the benefits of using contrast in such patients, both at rest and during stress, as derived from several single- and multi-center trials [2,5].Perhaps the Holly Grail of contrast echocardiography is the detection of myocardial perfusion. Although this does not constitute a clinical indication for use of contrast at present, several laboratories use intravenous contrast agents in echo-cardiography for the assessment of myocardial opacification, over and above the better endocardial definition. In this way, one can obtain improved image quality but also indication on myocardial perfusion simultaneously. There is now a wealth of data derived from several studies demonstrating similar information being obtained from myocardial contrast echo-cardiography (MCE) and single photon emission computed tomography (SPECT) imaging [6-10] in terms of myocardial perfusion in a qualitative way. It is important however for any imaging modality to be able to quantify the information, which gives more objective and less operator-dependent informa-tion. Intravenous injection of microbubbles for MCE allows measurements of myocardial blood volumes and myocardial blood velocities. Interestingly, the product of myocardial blood volume and velocity provides a measure for myocardial blood flow [11-13], which can now be quantified and ultimately pro-vide an alternative to positron emission tomography (PET) at a fraction of its cost. Unfortunately, what many centers currently use for assessing myocardial perfusion of the heart is SPECT, which of course only provides relative assessment of myocardial blood volumes between segments, thus lacking the measurement of myocardial perfusion. New methods of quantitation of myocardial perfusion have been detailed by Dr Luciano Agati during this symposium on contrast echo-cardiography. The qualitative and quantitative assessment of myocardial perfusion could thus provide additional and important information on patient outcomes. Contrast echocardiography is a safe procedure [14]. Echo contrast agents have an excellent safety profile compared to all the other contrast agents used for X-ray, radioactive materials used in nuclear medicine, computed tomography or magnetic resonance imaging as they have the least side effects [3]. How-ever, all contrast agents may induce allergic reactions, which physicians have to be prepared for and patients should there-fore be under medical supervision after contrast injection.T A K E  H O M E  M E S S A G E S :• Contrast echocardiography is commercially available and it is here to stay. Primary indication is to optimize assess-ment of left ventricular function at rest and during stress. It is alleged that some 20% of patients undergoing stress echocardiography have sub-optimal endocardial defini-tion. All those patients ought to have contrast!• Numerous research studies have demonstrated that intra-venous contrast injection may opacify the myocardium, thus providing unique information on myocardial perfu-sion. Although no specific clinical indication for perfusion currently exists, this concomitant information may be of great additional value during stress.• Finally, on the safety issue; transvenous administration of contrast agents for echocardiography is safe, certainly safer than many of the contrast agents used in radiology. All contrast agents may produce allergic reactions and echo contrast agents may do the same.R E F E R E N C E S 1. Mulvagh SL, DeMaria AN, Feinstein SB, Burns PN, et al. Contrast echocardiography: current and future applications. American Society of Echocardiography Task Force and Guide-lines for the use of ultrasound contrast in echocardiography. J Am Soc Echocardiogr 2000; 13:331. 2. Ikonomidis I, Holmes E, Narbuvold H, Bolstad B, Muan B, Nihoyannopoulos P. Left venticular wall motion assesment and endocardial border delineation after intravenous injection of Infoson™ during dobutamine stress echocardiography. Coro-nary Artery Disease 1998; 9:567-576. 3. Dijkmans PA, Visser CA, Kamp O. Adverse reactions to ul-trasound contrast agents: is the risk worth the benefit? Eur J Echocardiogr 2005; 6(5):363-6. 4. Hoffmann R, von Bardeleben S, ten Cate F, Borges AC, et al. Assessment of systolic left ventricular function: a multi-centre comparison of cineventriculography, cardiac magnetic reso-nance imaging, unenhanced and contrast-enhanced echocar-diography. Eur Heart J 2005; 26:607-616. 5. Hoffmann R, von Bardeleben S, Borges A, Kasprzak J, et al. Contrast-enhanced echocardiography improves interobserver agreement on assessment of ejection fraction-a multicenter study. J Am Soc Echocardiogr 2004; 17:503. 6. Amyot R, Morales MA, Rovai D. Contrast echocardiography for myocardial perfusion imaging using intravenous agents: pro-gress and promises. Eur J Echocardiogr 2000; 1:233-243. 7. Dijkmans PA, Juffermans LJM, Musters RJP, van Wamel A, et al. Microbubbles and ultrasound: from diagnosis to therapy. Eur J Echocardiogr 2004; 5:245-256. 8. Kaul S, Senior R, Dittrich H, Raval U, Khatter R, Lahiri A. Contrast echocardiography: comparison with 99m Tc-sesta-mibi single photon emission tomography. Circulation 1997; 96:785-92. 9. Sieswerda GT, Klein LJ, Kamp O, Aiazian EA, Lepper W, Visser FC, Hanrath P, Visser CA. Quantitative evaluation of myocardial perfusion in patients with revascularized myocar-dial infarction: comparison between intravenous myocardial contrast echocardiography and 99m Tc-sestamibi single photon emission computed tomography. Eur J Echocardiogr 2004; 5:41-50.64HOSPITAL CHRONICLES, SUPPLEMENT 2006 10. Jucquois I, Nihoyannopoulos P, D’Hontdt A-M, Roelants V, Robert A, Melin JA, Glass D, Vanoverschelde J-LJ. Compari-son of myocardial contrast echocardiography with NC100100 and Tc-99m sestamibi single photon emission computed to-mography for detection of resting myocardial perfusion abnor-malities in patients with previous myocardial infarction. Heart 2000; 83:518-524 11. Brodi V, Sanchis J, Losada A, Lopez-Lereu MP, Garcia D, Pellicer M, Chrono FJ, Llacer A. Usefulness of quantitative intravenous myocardial contrast echocardiography to analyze microvasculature perfusion in patients with a recent myocar-dial infarction and an open infarct-related artery: comparison with intracoronary myocardial contrast echocardiography. Eur J Echocardiogr 2005; 6:164-174.  12. Hagendorff A, Goeckritz A, Pfeiffer D, Becher H. Myocardial contrast echocardiography demonstrates myocardial hypoper-fusion in the LAD territory in patients with acute chest pain at rest-a prospective study using power Doppler harmonic imaging with intravenous bolus application. Eur J Echocardiogr 2004; 5:132-141.  13. Palmieri V, Arezzi E, Pezzullo S, Sabatella M, Celentano A. Inter- and intra-study reproducibility of contrast echocardiog-raphy for assessment of intraventricular septal wall perfusion rate in humans. Eur J Echocardiogr 2004; 5:367-374.  14. Becher H, Lofiego C, Mitchell A, Timperley J. Current indica-tions for contrast echocardiography imaging. Eur J Echocar-diogr 2005; 6 Suppl 2:S1-5. 

Clinical Applications of Contrast Echocardiography

In the past, routine clinical use of three-dimensional echocardiography has been hindered by the prolonged and tedious nature of data acquisition. Image processing is time consuming and requires dedicated manpower to generate three-dimensional reconstructions of the heart. The recent introduction of real-time three-dimensional echocardiographic imaging techniques has revolutionized echocardiography, as images are obtained in just one beat

THREE-DIMENSIONAL ECHOCARDIOGRAPHY65Three-Dimensional EchocardiographyPetros Nihoyannopoulos, MDIn the past, routine clinical use of three-dimensional echocardiography has been hindered by the prolonged and tedious nature of data acquisition. Image processing is time consuming and requires dedicated manpower to generate three-dimensional reconstructions of the heart. The recent introduction of real-time three-dimensional echocardiographic imaging techniques has revolutionized echocardiography, as im-ages are obtained in just one beat. Real-time three-dimensional imaging was initially performed using a sparse-array matrix transducer (2.5 or 3.5 MHz), which consisted of 256 non-simultaneously firing elements. This transducer acquired a pyramidal volume dataset measuring 60°x60° within a single heartbeat. Echocardiographic images were then displayed “on-line” using simultaneous orthogonal (B-scan images) as well as 2-3 parallel short-axis planes (C-scans). Similar to other 3D methods, the sparse-array transducer resulted in accurate left ventricular volumes, ejection fraction and mass when compared to gold standard tech-niques, such as magnetic resonance imaging (MRI) and radionuclide angiography. The sparse-array transducer was also used advantageously during stress testing, because all post-exercise images were simultaneously acquired during a single heart beat which was at higher peak stress heart rates compared to conventional stress tests. Full-matrix Array: A full-matrix array transducer (X4, Phillips Medical Systems, Andover, Massachusetts), which utilizes 3000 elements, has been developed.  This has resulted in (1) improved side-lobe performance (contrast resolution), (2) higher sensitivity and penetration, and (3) harmonic capabilities which may be used for both gray scale and contrast imaging. In addition, this transducer displays “on-line” 3D volume-rendered images and is also capable of displaying two simultaneous orthogonal two-dimensional imaging planes (i.e., biplane imaging). C L I N I C A L  A P P L I C A T I O N S  A R E  M U L T I P L E  One of the most important requests in cardiac imaging is the easy and accurate assessment of left ventricular (LV) function. With real-time 3D imaging, LV vol-umes can be obtained quickly and accurately. The left ventricle (apical 4-, 3- and 2-chamber views) is usually acquired from the apical window using a wide-angled acquisition. Images are displayed either using orthogonal long-axis views, or using multiple short-axis views, obtained at the level of the left ventricular apex, papillary muscles and the base. In contrast to 2D echocardiography, real-time 3D echocardiography does not rely on geometric assumptions to calculate left ventricular volumes. This constitutes a real advantage in ventricles with odd shapes and wall motion abnormalities. Similarly, the unique geometrical shape of the right ventricle has precluded accurate quantification CARDIOLOGY UPDATE 2006Reader & Consultant Cardiologist, Hammersmith Hospital, NHLI, Imperial College London, e-mail: p.nihoyannopoulos@imperial.ac.ukHOSPITAL CHRONICLES 2006, SUPPLEMENT: 65–66Address for correspondence:Petros Nihoyannopoulose-mail: p.nihoyannopoulos@imperial.ac.uk66HOSPITAL CHRONICLES, SUPPLEMENT 2006using traditional echocardiographic methods. Transthoracic three-dimensional echocardiography has the potential of over-coming these limitations resulting in accurate measurements of right ventricular size and function. Quantification of left ventricular volumes and mass using real-time 3D echocardiography can be performed from an apical wide-angled acquisition using different methods. Cur-rently, data analysis is performed on a desktop or laptop com-puter with dedicated 3D software (4D LV analysis, TomTec GMBH, Munich, Germany). Since a data set comprises the entire left ventricular volume, multiple slices can be obtained from the base to the apex of the heart to evaluate wall motion. This acquisition can be combined with the use of an infusion of contrast particularly in patients with difficult acoustic window in whom it might be of benefit to improve the delineation of the endocardial border.Biventricular pacing in patients with severe left ventricular dysfunction has shown to improve symptoms, but the mecha-nism responsible for this benefit is still the subject of contro-versy. Three-dimensional echocardiography may be helpful to elucidate this mechanism due to its ability to clearly display changes in both global and regional volumes during different biventricular pacing settings. Preliminary observations dem-onstrate that regional contractility occurs during biventricular pacing in a more synchronized manner.More accurate valve assessment: Mitral valve can now be readily displayed from transthoracic images and both leaflets can be described in a comprehensive manner. Thus, degenera-tive valves with or without prolapse can be evaluated and a decision to repair can be made in advance of the operation. Other applications include complex congenital heart disease, aortic valve and root pathology. R E F E R E N C E S 1.  Jenkins C, Bricknell K, Hanekom L, et al. Reproducibility and accuracy of echocardiographic measurements of left ventricu-lar parameters using real-time three-dimentional echocardiog-raphy. J Am Coll Cardiol 2004; 44:878-86.  2.  Zeidan Z, Erbel R, Barkhausen J, et al. Analysis of global sys-tolic and diastolic left ventricular performance using volume-time curves by real-time three-dimentional echocardiography. J Am Soc Echocardiogr 2003; 16:29-37.  3.  Gutierrez-Chico JL, Zamorano JL, Perez de Isla L, et al. Comparison of left ventricular volumes and ejection fractions measured by three-dimensional echocardiography versus by two-dimensional echocardiography and cardiac magnetic reso-nance in patients with various cardiomyopathies. Am J Cardiol 2005; 95:809-13.  4.  Mor-Avi V, Sugeng L, Weinart L, et al. Fast measurement of left ventricular mass with real-time three-dimensional echo-cardiography: comparison with magnetic resonance imaging. Circulation 2004; 110:1814-18.  5.  Kapetanakis S, Kearney MT, Siva A, et al. Real-time three-dimensional echocardiography. A novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation 2005; 112:992-1000. 

Three-Dimensional Echocardiography

This brief overview relates to the recent introduction of real-time three-dimensional echocardiographic imaging techniques, which has revolutionized echocardiography, as images are obtained in just one beat. A great potential lies ahead as clinical applications are multiple

Three-Dimensional EchocardiographyPetros Nihoyannopoulos, MD, FRCPA B S T R A C TThis brief overview relates to the recent introduction of real-time three-dimensional echocardiographic imaging techniques, which has revolutionized echocardiography, as images are obtained in just one beat. A great potential lies ahead as clinical ap-plications are multiple.T H R E E - D I M E N S I O N A L  E C H O C A R D I O G R A P H YIn the past, routine clinical use of three-dimensional echocardiography has been hindered by the prolonged and tedious nature of data acquisition. Image processing is time consuming and requires dedicated manpower to generate three-dimensional reconstructions of the heart. The recent introduction of real-time three-dimensional echocardiographic imaging techniques has revolutionized echocardiography, as images are obtained in just one beat.1,2Real-time three-dimensional imaging was initially performed using a sparse-array matrix transducer (2.5 or 3.5 MHz), which consisted of 256 non-simultaneously firing elements. This transducer acquired a pyramidal volume dataset measuring 60°x60° within a single heartbeat. Echocardiographic images were then displayed “on-line” using simultaneous orthogonal (B-scan images) as well as 2-3 parallel short-axis planes (C-scans).Similar to other 3D methods, the sparse-array transducer resulted in accurate left ventricular volumes, ejection fraction and mass when compared to gold standard tech-niques, such as magnetic resonance imaging (MRI) and radionuclide angiography.3,4 The sparse-array transducer was also used advantageously during stress testing, because all post-exercise images were simultaneously acquired during a single heart beat which was at higher peak stress heart rates compared to conventional stress tests.Full-matrix Array: A full-matrix array transducer (X4, Phillips Medical Systems, Andover, Massachusetts), which utilizes 3000 elements, has been developed.5 This has resulted in (1) improved side-lobe performance (contrast resolution), (2) higher sensitivity and penetration, and (3) harmonic capabilities which may be used for both gray scale and contrast imaging. In addition, this transducer displays “on-line” 3D volume-rendered images and is also capable of displaying two simultaneous orthogonal two-dimensional imaging planes (i.e., biplane imaging).EDITORIALHammersmith Hospital, London, UKHOSPITAL CHRONICLES 2008, 3(4): 159–160Correspondence to:Petros Nihoyannopoulos, MD, FRCPProfessor of CardiologyHammersmith Hospital, Du Cane RoadLondon W12 0HS, UKE-mail: p.nihoyannopoulos@imperial.ac.ukKEY WORDS: echocardiography; three-dimensional echocardiography; valvular heart diseaseLIST OF ABBREVIATIONS: MRI = magnetic resonance imagingLV = left ventric-le(-ular)Presented in part at “Cardiology Update 2006”, International Cardiology Symposium of Evagelismos General Hospital of Athens, Athens, Greece, April 13-15, 2006160HOSPITAL CHRONICLES 3(4), 2008C L I N I C A L  A P P L I C A T I O N S  A R E  M U L T I P L EOne of the most important requests in cardiac imaging is the easy and accurate assessment of left ventricular (LV) function.6-12 With real-time 3D imaging, LV volumes can be obtained quickly and accurately. The left ventricle (apical 4-, 3- and 2-chamber views) is usually acquired from the apical window using a wide-angled acquisition. Images are displayed either using orthogonal long-axis views, or using multiple short-axis views, obtained at the level of the left ventricular apex, papillary muscles and the base.In contrast to 2D echocardiography, real-time 3D echocar-diography does not rely on geometric assumptions to calculate left ventricular volumes. This constitutes a real advantage in ventricles with odd shapes and wall motion abnormalities. Similarly, the unique geometrical shape of the right ventri-cle has precluded accurate quantification using traditional echocardiographic methods. Transthoracic three-dimensional echocardiography has the potential of overcoming these limi-tations resulting in accurate measurements of right ventricular size and function.Quantification of left ventricular volumes and mass using real-time 3D echocardiography can be performed from an api-cal wide-angled acquisition using different methods. Currently, data analysis is performed on a desktop or laptop computer with dedicated 3D software (4D LV analysis, TomTec GMBH, Munich, Germany). Since a data set comprises the entire left ventricular volume, multiple slices can be obtained from the base to the apex of the heart to evaluate wall motion. This acquisition can be combined with the use of an infusion of contrast particularly in patients with difficult acoustic window in whom it might be of benefit to improve the delineation of the endocardial border.Biventricular pacing in patients with severe left ventricular dysfunction has shown to improve symptoms, but the mecha-nism responsible for this benefit is still the subject of contro-versy. Three-dimensional echocardiography may be helpful to elucidate this mechanism due to its ability to clearly display changes in both global and regional volumes during different biventricular pacing settings. Preliminary observations dem-onstrate that regional contractility occurs during biventricular pacing in a more synchronized manner.6More accurate valve assessment: Mitral valve can now be readily displayed from transthoracic images and both leaflets can be described in a comprehensive manner.9,10 Thus, degen-erative valves with or without prolapse can be evaluated and a decision to repair can be made in advance of the operation. Other applications include complex congenital heart disease, aortic valve and root pathology.R E F E R E N C E S 1. Jenkins C, Bricknell K, Hanekom L, et al. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimentional echocardiogra-phy. J Am Coll Cardiol 2004; 44:878-886. 2. Zeidan Z, Erbel R, Barkhausen J, et al. Analysis of global systo-lic and diastolic left ventricular performance using volume-time curves by real-time three-dimentional echocardiography. J Am Soc Echocardiogr 2003; 16:29-37. 3. Gutierrez-Chico JL, Zamorano JL, Perez de Isla L, et al. Com-parison of left ventricular volumes and ejection fractions meas-ured by three-dimensional echocardiography versus by two-di-mensional echocardiography and cardiac magnetic resonance in patients with various cardiomyopathies. Am J Cardiol 2005; 95:809-813. 4. Mor-Avi V, Sugeng L, Weinart L, et al. Fast measurement of left ventricular mass with real-time three-dimensional echocar-diography: comparison with magnetic resonance imaging. Cir-culation 2004; 110:1814-1818. 5. Salgo IS. Three-dimensional echocardiographic technology. Cardiol Clin 2007;25:231-239. 6. Kapetanakis S, Kearney MT, Siva A, et al. Real-time three-di-mensional echocardiography. A novel technique to quantify glo-bal left ventricular mechanical dyssynchrony. Circulation 2005; 112:992-1000. 7. Kort S. Real-time 3-dimensional echocardiography for pros-thetic valve endocarditis: initial experience. J Am Soc Echocar-diogr 2006;19:130-139. 8. Hare JL, Jenkins C, Nakatani S, Ogawa A, Yu CM, Marwick TH. Feasibility and clinical decision-making with 3D echocardi-ography in routine practice. Heart 2008;94:440-445. Epub 2007 Jul 30. 9. Agricola E, Oppizzi M, Pisani M, Maisano F, Margonato A. Accuracy of real-time 3D echocardiography in the evaluation of functional anatomy of mitral regurgitation. Int J Cardiol 2008;127:342-349. Epub 2007 Jul 23. 10. Song JM, Kim MJ, Kim YJ, et al. Three-dimensional character-istics of functional mitral regurgitation in patients with severe left ventricular dysfunction: a real-time three-dimensional col-our Doppler echocardiography study. Heart 2008;94:590-596. Epub 2007 Jul 23. 11. Hung J, Lang R, Flachskampf F, et al; ASE. 3D echocardiogra-phy: a review of the current status and future directions. J Am Soc Echocardiogr 2007;20:213-233. 12. Cheng TO. Clinical application of real-time three-dimensional echocardiography. J Cardiol 2007;49:213-214.

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Clinical Applications of Contrast Echocardiography

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