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Contrast Echocardiography

Opacification of the right heart cavities with dense ultrasonic reflectances during intravenous contrast injection was first applied clinically in 1968.123 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.124 Since room-air microbubbles with the diameter of pulmonary capillaries persist intact 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.125 Identification of intracardiac shunts, particularly patent foramen ovale in patients with unexplained cerebral ischemia (Fig. 15–55), remains a frequent indication for contrast echocardiography. Simple agitated normal saline solution remains the most commonly used contrast agent for such studies.   Figure 15–55. Contrast microbubble injection demonstrating a shunt (arrow) from the right atrium (RA) to left atrium (LA). RV = right ventricle; LV = left ventricle. Echocardiographic opacification of the LV cavity and myocardium by intracardiac or intravenous injection is now easily performed.126–128 The presence of echocardiographic contrast within the myocardium after such injections reflects the spatial distribution of coronary blood flow (CBF) and is valuable in identifying collateral CBF and the absence of reflow following reperfusion therapy of acute myocardial infarction (AMI).129,130 Of significance, the presence of microcirculatory flow and integrity in these studies was a reliable predictor of viable myocardium.129 Since direct injection of coronary contrast into the left heart or aorta (Fig. 15–56) is limited by its invasive nature, 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 dissolving in blood can be increased by utilizing a shell or surface modifying agent which inhibits the leakage 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.131,132   Figure 15–56. Short-axis plane through the left ventricle (LV) before (left) and after (right) injection of microbubbles into the aortic root. The myocardium is densely opacified on the right. (From Hagan AD, DeMaria AN. Clinical Applications of Two-Dimensional Echocardiography and Cardiac Doppler. Boston: Little, Brown; 1989. With permission.) Intravenous injection of stabilized solutions of microbubbles opacifies the LV 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.133 Marginal Doppler spectral tracings in cases of MR, tricuspid regurgitation, and aortic stenosis often improved dramatically after contrast injection, facilitating the quantitation of valvular lesions and pulmonary hypertension.134 In addition to new contrast agents, novel imaging technology directed to the amplification of contrast signals are also available. Harmonic imaging amplifies the ultrasonic backscatter from contrast microbubbles (which resonate in an ultrasonic field) relative to the returning signal from myocardium (which does not resonate). (Fig. 15–57). As discussed above, tissue harmonic imaging can also be used to visualize cardiac structures in the absence of contrast injection: this technique decreases clutter and other artifacts, often improving endocardial definition (Fig. 15–58).   Figure 15–57. Harmonic imaging after intravenous injection of echocardiographic contrast. Endocardial border definition before injection is fair (upper panel) but is markedly improved with harmonic imaging following contrast injection (lower panel).   Figure 15–58. Tissue harmonic imaging. The upper panel shows a parasternal long-exis new figure view obtained with standard (fundamental) imaging. Endocardial definition is poor, but is markedly enhanced with tissue harmonic imaging (lower panel). 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 suited to detect the changing signals produced by movement and/or dissolution of contrast microbubbles.47 Exposure to ultrasound energy can produce not only microbubble resonation but also destruction. Intermittent electrocardiographic (ECG-gated) imaging rather than continuous ultrasound transmission can also thereby prolong microbubble persistence and amplify contrast signals by limiting bubble destruction. Most recently, low power, real-time techniques have been developed that enable imaging of myocardial opacification without the need for ECG gating and intermittent imaging. 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.135,136 Myocardial contrast echocardiography can identify infarct areas in AMI, document the absence of microcirculatory flow after epicardial coronary reperfusion ("no-reflow" phenomenon), and predict postinfarction viability.129 Intravenous injection of contrast agents also permits visualization of intramyocardial vessels.134,137 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.