Enormous strides have been made in cardiovascular ultrasound, as experimental advances are rapidly converted into practical clinical tools. Notable among recent developments are the clinical application of contrast echocardiography for perfusion imaging, the growing acceptance of three-dimensional imaging among cardiac specialists, identification of the clinical utility of tissue Doppler echocardiography, and the advent of ultrasound stethoscopy.
A major problem in echocardiography has been the difficulty in clearly visualizing cardiac structures in patients with suboptimal acoustic windows. The high signal-to-noise ratio and considerable clutter result in poor delineation of chamber borders. Innovations in imaging technology introduced to solve this problem include broadband transducers, Doppler imaging of tissue, moving target indicators, tissue harmonic imaging, and parallel processing. These functions provide crisp definition of tissue structures- myocardium in particular-and have become widely used.
Broadband transducers enable imaging with higher frequency even at maximum depths. Power Doppler imaging, in which the amplitude or power component of the myocardial signal is processed, yields better definition of myocardial borders, improving assessment of cavity volume and function as well as regional wall motion.
The realization that tissue yields harmonic signals, and that these signals can be incorporated into a two-dimensional display, led to the development of tissue harmonic imaging. This modality has become standard in most ultrasound instruments and is being used in echocardiographic practice as an adjuvant mode in cardiac examinations.
The use of Doppler modalities in the assessment of flow abnormalities and hemodynamic derangements is now commonplace. Doppler imaging can also be used to derive the velocity of motion in different regions of myocardium. Its diagnostic potential in evaluating myocardial kinetics is under intense study.
Using pulsed Doppler or the velocity mode of tissue Doppler imaging, the examiner can quantify the motion of the mitral and tricuspid annuli during both systole and diastole. Recent investigations indicate that mitral annular motion could aid in differentiating constrictive pericarditis from restrictive cardiomyopathy, even when flow velocity data might seem similar.
Other studies suggest that tissue Doppler imaging may also be of use in the identification of transplant rejection. It is conceivable that this technique could avoid excessive biopsies in transplant patients with normal tissue Doppler data.
Power or energy mode Doppler is already used in imaging cardiac structures in patients with technically difficult acoustic windows and in perfusion imaging. The next few years should define the precise clinical indications for tissue Doppler echocardiography.
3-D ECHOCARDIOGRAPHY
Three-dimensional echocardiography can be performed in real-time or within a few minutes in a range of clinical settings, including the operating room. Using conventional echocardiographic instruments equipped with multiplane transesophageal or transthoracic transducers, the examiner can acquire and quickly process sequential images and derive multiple 3-D projections. A freehand transducer can be applied to acquire images in a simpler manner.
Advances in image processing enable sectioning of the heart right from the 3-D image, without having to reprocess the raw data. The accuracy of 3-D echocardiography in the estimation of left and right ventricular volume, mass, shape, and function, as well as atrial volumes, has been well validated. In addition, qualitative and quantitative information is easily obtained for valvular lesions (Figure 1), as well as for congenital heart lesions.1
Interest has been growing in the translation of 3-D ultrasound data into physical models of the human heart. Physical replicas of heart structures and pathologic lesions can be fabricated using stereolithography or ultraviolet light-exposure rapid prototyping. This and other modeling techniques could have important applications in preoperative planning for cardiac surgery, as well as in teaching and training new physicians and in explaining cardiac pathology and planned corrective procedures to patients and families.
Intracardiac flow jets can also be visualized in all their dimensions by processing color Doppler signals. Three-dimensional color Doppler echocardiography aids in the study of mechanisms of abnormal flow and has the potential to assist in the quantitation of flow jets. Tissue Doppler data can also be developed into a 3-D tissue Doppler image that describes a physiologic event-myocardial kinetics-at any given time in the cardiac cycle. Thus, 3-D echocardiography can incorporate not only morphology but also physiology.
HANDHELD ECHO
For more than a century, the stethoscope has been part of the image of a physician. While the traditional stethoscope, perhaps more appropriately termed a stethophone, provides valuable information on cardiac dynamics, it does not display the anatomy or movements of the cardiac structures. Stethoscopy using miniaturized ultrasound instruments, or ultrasound stethoscopy, is becoming a clinical reality. A number of such small instruments are commercially available.
We have explored the potential of a small lightweight 2-D and color Doppler instrument in the evaluation of cardiac patients.2 By taking this instrument around the hospital during clinical rounds, we are able to perform a brief echocardiography exam instantly at the bedside after physical examination of the patient.
We have used the instrument to obtain cardiac imaging studies of diagnostic quality and to assess left and right ventricular function, pericardial effusion, and any major morphologic, functional, or flow abnormalities. Comparison of bedside ultrasound stethoscopic information with subsequent comprehensive echocardiographic examination in 30 patients indicated no differences between conventional and bedside imaging in the recognition of major cardiac pathology.
While various modalities of cardiovascular ultrasound have provided reliable evaluation of cardiac morphology, intracardiac flow jets, and hemodynamics, one major challenge has remained: assessment of coronary and myocardial blood flow. Following two decades of investigational work, contrast echocardiography is on the threshold of clinical application. A considerable body of experimental work has laid the foundation for contrast echo by illustrating that ultrasound contrast agents that follow the blood cells can opacify cardiac chambers, enhance myocardial signals, and display hypo- and nonperfused myocardial regions. These agents thus identify infarcted and ischemic areas and aid in gauging myocardial viability in dysfunctional zones by demonstrating microvascular integrity.
Many new biologically safe contrast agents have been developed that are small in size (microbubbles of less than 7 mm) and persist for sufficient time periods to allow systematic echocardiographic imaging. Many contain a high-molecular-weight gas such as perfluorocarbon, although a few contain air. The shell composition has included albumin, saccharides, and synthetic polymers.
Two agents, Optison and Levovist, have been approved for clinical application for better delineation of ventricular cavity borders and enhancement of Doppler signals. Indeed, contrast agents are used for these purposes in patients with suboptimal acoustic windows and during stress echocardiography to better assess global and regional ventricular function and Doppler data.
PERFUSION STUDIES
Experimental and clinical research work using many agents has shown their potential in myocardial perfusion imaging. This research has been aided by the development of harmonic ultrasound imaging, which exploits the microbubble response to ultrasound emission. Processing the harmonic signals of microbubbles doubles the frequency of transmitted ultrasound received, enhancing the sensitivity of perfusion image analysis (Figure 2). Work in this area prompted the observation that tissue also gives harmonic signals, and this finding has translated into the clinical development of tissue harmonic imaging.
An obstacle encountered in early attempts at perfusion imaging-bubble destruction by ultrasound-resulted in false perfusion defects. This problem has been overcome by intermittent harmonic imaging, which allows time for instant replenishment of contrast agents during cardiac cycles and, thus, reliable myocardial enhancement. Intermittent imaging can be performed by triggering at any part of the cardiac cycle as well at intervals of one, two, four, or any number of, beats.
Clinical studies using intermittent imaging have shown that transvenous contrast agents enable perfusion imaging to display the myocardium in a variety of clinical situations. These include normal myocardial perfusion, evidenced by reasonably uniform myocardial enhancement (i.e., an increase in brightness); infarcted regions, evidenced by lack of myocardial signal enhancement or reduced brightness compared with normal regions; and viable myocardium in scenarios of reperfusion or hibernation, evidenced by normal myocardial enhancement in dysfunctional regions.
To assess coronary stenosis, some form of stress imaging must be used. Kaul and colleagues administered Optison during dipyridamole stress in a group of patients with established and suspected coronary artery disease.3 They found that contrast echo had excellent sensitivity and specificity when compared with nuclear imaging for the diagnosis of coronary disease, recognition of both fixed and reversible perfusion defects, and identification of myocardial segments involved in ischemia or infarction. Porter and associates performed systematic investigations during exercise and dobutamine stress and demonstrated diagnostic accuracy equal to nuclear imaging and coronary angiography.4
The largest clinical experience with perfusion imaging is from the laboratory of Morcerf's group in Brazil.5 They have carried out perfusion studies in more than 1000 patients employing a perfluorocarbon agent and adenosine bolus stress. In this protocol, imaging is performed at baseline without contrast, and then with contrast followed by adenosine administration. The ultrasound emission power and other technical controls are adjusted so that myocardium exhibits increased brightness with contrast at rest but with less intensity than that observed in the cavity. Following the adenosine bolus, myocardium perfused by a coronary artery with a stenosis demonstrates lack of further enhancement, while normal myocardium displays a further increase in brightness. This protocol has demonstrated excellent diagnostic accuracy in single- and multivessel disease in various clinical scenarios.
In a collaborative study with Nesser and associates, our group compared an adenosine bolus protocol with an adenosine infusion protocol and noted equal diagnostic accuracy in the identification of both fixed and reversible perfusion defects.6 Work by many investigators has clearly documented that perfusion assessment with triggered intermittent imaging could be a reliable clinical technique.
Another approach being examined is the use of power Doppler imaging during contrast to process the signals emanating from ultrasound-microbubble interaction. As ultrasound amplitude is gradually increased, contrast agents first exhibit a linear response, then a harmonic response, and eventually burst. Doppler imaging can be used to process such transitional events, and normally perfused and nonperfused zones can be recognized by the presence of intense Doppler signals, which indicate normal myocardium, and decreased or absent Doppler signals, indicating ischemic or infarcted myocardium (Figure 3). This approach awaits systematic clinical investigation.
An exciting development has been real-time perfusion imaging employing low emission power. Bubble destruction is reduced, and continuous imaging can be performed, enabling evaluation of not only myocardial perfusion but also wall motion during rest and stress. Early experience with this approach has been encouraging. If prospective studies attest to its accuracy, this method has the potential to be the most useful clinically.
While continuing to make valuable contributions to daily patient care, echocardiography is reaching new heights. The next challenge could be coronary artery visualization and direct detection of lesions in the coronary tree using surface imaging.
DR. PANDIAN is director of cardiovascular imaging and hemodynamics at Tufts-New England Medical Center in Boston.
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References
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3. Kaul S, Senior R, Dittrich H, et al. Detection of coronary artery disease with myocardial contrast echocardiography: comparison with Tc-sestamibi single photon emission tomography. Circulation 1997;96:785-792.
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