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Opacification of the right heart cavities with dense ultrasonic reflectances during intravenous contrast injection was first applied clinically in 1968.192 Subsequently, it became clear that the origin of the dense intracavitary echoes were microbubbles within the injectate, and that any agitated liquid injected intravenously caused the effect.193 Since room-air microbubbles with the diameter of pulmonary capillaries persist in blood for less than 1 s before dissolving, agitated agents injected intravenously cannot cross the lungs and enter the left-sided cardiac chambers. Thus, the presence of echocardiographic contrast entering left heart chambers after intravenous injection of an agitated liquid indicates the presence of a right-to-left shunt.194,195

Identification of intracardiac shunts, particularly patent foramen ovale in patients with unexplained cerebral ischemia (Q-hB; Fig. 13-55), remains the most frequent indication for contrast echocardiography.!96 Simple agitated normal saline solution remains the most commonly used contrast agent for such studies.

In recent years, many attempts have been made to achieve echocardiographic opacification of the LV cavity and myocardium.197-200 Initial attempts utilized direct left-sided administration. Injection of agitated saline or other fluids into the LV or aorta causes echocardiographic opacification of those chambers and has been used as an alternative to angiography to evaluate mitral and aortic regurgitation.194 In addition, injection of sonicated radiographic contrast agents into the aortic root or coronary arteries can produce myocardial opacification^6! (Q-hB; Fig. 1356). The presence of echocardiographic contrast within the myocardium after such injections reflects the spatial distribution of coronary blood flow (CBF)i98 and is valuable in identifying collateral CBF and the absence of reflow following reperfusion therapy of acute myocardial infarction (MI).202-210 Of significance, the presence of microcirculatory flow and integrity in these studies was a reliable predictor of viable myocardium.207-209

Direct injection of coronary contrast into the left heart is limited by its invasive nature. Therefore, stabilized solutions of microbubbles have been developed which can traverse the pulmonary capillary bed in high concentration after intravenous injection. These new ultrasonic contrast agents have been designed to achieve prolonged bubble persistence or survival after injection into blood. The persistence time of a bubble prior to disolving in blood can be increased by utilizing a shell or surface modifying of gas across the bubble surface. Alternatively, prolonged bubble survival can be achieved by utilizing a dense, high-molecular-weight gas with a reduced capacity to diffuse across the bubble shell and a low saturation constant in blood, which favors return of gas back into the bubble. Therefore, the new ultrasonic contrast agents utilize shells made of human serum albumin, liposomes, or even biodegradable poliment materials, and the fluorocarbon gases, which are dense and poorly soluble. These new microbubble agents are all capable of producing dense, high-intensity signals not only within the LV but also within the myocardium following intravenous injection.210a,210b

Efforts to produce stabilized solutions of microbubbles have now resulted in a commercially available agent, Optison, which is composed of a perfluorocarbon gas in an albumin shell. Intravenous injection of Optison opacifies the left ventricle in nearly all patients, thereby facilitating identification of the endomyocardial border. This capacity has found its greatest application in stress echocardiography, where detection of the endocardium is of fundamental importance in recognizing abnormal contraction produced by ischemia. By intensifying backscatter within the intracardiac cavities, new ultrasonic agents also enhance Doppler recording of flow abnormalities.^!! Marginal Doppler spectral tracings in cases of mitral regurgitation, tricuspid regurgitation, and aortic stenosis often improved dramatically after contrast injection, facilitating the quantitation of valvular lesions and pulmonary hypertension.212-216 In addition to new contrast agents, novel imaging technology directed to the amplification of contrast signals are also available. Second harmonic imaging enhances the ultrasonic backscatter from contrast microbubbles (which resonate in an ultrasonic field) while decreasing the returning signal from myocardium (which does not resonate).217-219 (Fig. 13-57). Power Doppler imaging is a method that correlates signals between successfully transmitted pulses to derive images of moving blood or cardiac structures. Power Doppler techniques are especially well delineated to detect the changing signals produced by movement and/or dissolution of contrast microbubbles.46 Finally, since exposure to ultrasound energy can produce microbubble destruction, intermittent electrocardiography (ECG) gated rather than continuous ultrasound transmission can also prolong microbubble persistence and amplify contrast signals.220,221 When combined with the new ultrasonic contrast agents, these refined imaging modalities can achieve visualization of myocardial opacification following intravenous drug administration, thereby delineating myocardial perfusion. Initial studies indicate that myocardial contrast echocardiography can yield information regarding myocardial perfusion comparable to that obtainable by radionuclide techniques and can be of value in delineating coronary artery stenoses.221a,221b Intravenous injection of new contrast agents may actually permit visualization of intramyocardial vessels

Fig. 13-58).214-217'221c The ability to delineate regional myocardial perfusion is a major step forward in noninvasive imaging and can be expected to provide important information regarding coronary artery disease (CAD) in the near future.

Figure 13-57: Harmonic imaging with second-generation echocardiographic contrast. Endocardial border definition before injection is fair (upperpanel) but is markedly improved with harmonic imaging following contrast injection (lower panel).

In addition to new contrast agents, novel imaging technologies directed to the amplification of contrast signals are also available. For example, second-harmonic imaging enhances the ultrasonic backscatter from contrast microbubbles (which resonate in an ultrasonic field) while decreasing the returning signal from myocardium (which does not resonate)217-219 (Fig. 13-57). Early after contrast injection, second-harmonic imaging increases the cavity-to-myocardium contrast intensity ratio, improving visualization of the left ventricular cavity. Second-harmonic imaging may also enhance the myocardial contrast phase, which follows LV cavity opacification with second-generation contrast agents.217-219 As exposure to ultrasound energy can produce microbubble destruction, intermittent rather than continuous ultrasound transmission can also prolong microbubble persistence and amplify contrast signals.220,221,210b In recent years, harmonic imaging has been used to visualize cardiac structures in the absence of contrast injection. This tissue harmonic imaging decreases clutter and other artifacts, often improving endocardial definition (&H0; Fig. 13-58/1).


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