New contrast agents are revolutionizing clinical echocardiography by enhancing the resulting images (Fig. 1). An albumin-coated air microbubbles agent was the first of these new agents, but has been replaced by an albumin-coated fluorocarbon-based bubbles agent that persists much longer and provides brighter echos. Saccharide-coated fluorocarbon bubbles, phospholipid-coated fluorocarbon bubbles, and fluorocarbon emulsions are available among many others. A large number of commercial bubbles will be available soon. Agents that will better opacify the myocardium to see whether or not there is perfusion throughout the entire heart muscle are under development.

The use of harmonic imaging, intermittent imaging, power Doppler, and how the contrast is analyzed are providing better images.

Harmonic imaging

Harmonic imaging is a major breakthrough. When an ultrasonic beam interacts with a bubble it expands and contracts and thus sends off a secondary frequency, a harmonic frequency, usually at a multiple of the transmitted frequency. Since bubbles oscillate and noise and for the most part tissue do not oscillate, the signal-to-noise ratio can be enhanced, allowing bubbles and echo to be better distinguished.

Intermittent Imaging

Intermittent imaging of every third or fifth cardiac cycle allows for better opacification of the myocardium. The Doppler signal itself interacts with the bubbles not only by oscillation but by actually destroying the bubble. In contrast, continuous imaging yields a very faint opacification because the ultrasonic beam is destroying the bubbles.

Power Doppler

Power Doppler is an even more powerful way to destroy bubbles to yield a very strong signal to enhance the contrast effect. Power modulation, another new technique offering great promise, hits the heart with a very high mechanical index, 0.7, to destroy all the bubbles. The myocardium is then echo free, which is followed by gradual reperfusion and bubble reaccumulation in the myocardium, allowing time to evaluate myocardial reperfusion.

Analysis of Contrast

Video densitometry and digital enhancement are being used to improve analysis of the contrast agents. Investigators are attempting quantification using video densitometry to see the change in amplitude of the signal of the contrast agent in the perfused area versus the nonperfused area. Kaul has shown that digital enhancement can produce striking images. However, this process is extremely intensive and the reproducibility of these studies by other investigators has been limited to date. Logistical and technical details must be worked out, but there is great optimism that it will be possible to reproduce such digital images in a consistent, reliable fashion.

Contrast echocardiography using harmonic imaging is being used for endocardial border definition by opacifying the left ventricular cavity. This has been approved for clinical use in the United States, and patients with coronary artery disease will warrant this application.

The most intriguing application and the one being most intensely investigated is for myocardial perfusion. The bubbles enhance the left ventricular cavity by passing through the right side, passing into the left ventricle, outlining the cavity and providing greater definition of the septal and lateral walls. The clinical aim is to consistently see the lack of myocardial perfusion resulting from coronary obstruction.

Kaul has shown that harmonic imaging of the ischemic muscle is a brighter more consistent recording that better shows the homogeneous lack of perfusion in the myocardium. Work from Porter has shown the lack of perfusion when ischemia is produced.

Broadband Tissue Imaging

Broadband multi-frequency transducers with a lower frequency that provides better penetration and a higher frequency that improves resolution are becoming standard. Replacing lower power transducers are 4-2 MHz broadband transducer, 7-4 MHz or an 11-8 MHz transducer.

Coronary artery visualization is being actively investigated. The left anterior descending is viewed transthoracically as a sample site of the coronary circulation based on the assumption that coronary artery disease is a diffuse process. Figures 2 to 4 demonstrate the utility of high frequency imaging. This technique is being developed to noninvasively detect subclinical coronary atherosclerosis to better define which patients should be treated with lipid lowering agents, statins, and aspirin.

Harmonic Tissue Imaging

Harmonic imaging of tissue clearly enhances endocardial and myocardial visualization (Fig. 5), and is available on virtually every instrument today. Tissue produces a harmonic signal and by sampling the signal returning from tissue a greater signal-to-noise ratio is achieved. Harmonic imaging of tissue requires a high mechanical index, whereas harmonic imaging of bubbles requires a low index. However, because this method can make things appear thicker, such as valves, it is necessary to consider this when viewing harmonic tissue images. This technique has become a standard way of doing most stress echocardiograms in most laboratories.

Tissue Doppler

Tissue Doppler can be used to quantitate wall motion, look at various parts of the heart, assess systolic and diastolic function as well as examine the mitral annulus for diastolic function. The concept of myocardial strain to improve quantitating myocardial contraction, and a variety of other ways to quantify ventricular function are also being investigated. The ability to automatically track the color Doppler to measure flow by measuring the diameter and the velocity is being developed. These developments will provide more direct myocardial indicators, rather than the hemodynamic indicators presently used.

The amplitude of motion of the annulus is a very important prognostic indicator of left ventricular function as shown by a 1997 study using M-mode echocardiography. In people with heart failure over age 65 years with an amplitude of the annulus greater than 10 mm, the one year mortality was zero. However, if the amplitude was less than 6 mm, there was about a 35% risk of mortality. Recording the motion using tissue Doppler of the annulus combined with the mitral flow allows for improved evaluation of the hemodynamics and myocardial function.

Tissue Doppler has been used for the differentiation of restrictive cardiomyopathy and constrictive pericarditis. Any condition that restricts the myocardium will cause abnormal annulus motion with a short E and a tall A. But in the case of a pericardial problem and a normal myocardium, the annular motion is normal because of the normal myocardium. Work from Garcia shows that the resting systolic velocity, roughly 10 cm/second, increases to about 30-40 cm/second with dobutamine in normal myocardium. But, if ischemia is present there is no increase in velocity in response to dobutamine.

Automated quantitation will be the likely result of improved endocardial border definition. This could be done on-line on the ultrasound instrument or off-line on a computer. The improved definition of the endocardium needed for on-line measurements will come from harmonic tissue imaging and the new contrast agents.

3-D echocardiography is an area of active investigation and has been used in valvular and congenital heart diseases. Potential applications are assessing left ventricular volumes, which will clearly be more accurate than 2-D, and for stress echo.

Parallel processing is an important technique. A limitation of ultrasound is the fact that sound moves slowly. Parallel processing samples one signal multiple times. One technique samples the signal 16 times, effectively increasing the speed by a factor of 16, with the goal of producing real-time 3-D echo. A prototype instrument for parallel processing is producing some very interesting and encouraging work. Real-time 3-D echocardiography will be a reality, and it will have a major impact on cardiac ultrasound.

Handheld Echocardiographs

Small handheld echographs being developed will provide the ability to put a transducer on a patient's chest at the bedside to actually see inside the heart and obtain either a color or black and white 2-D echocardiogram. This will have a major impact on the use of cardiac ultrasound. A former president of the American College of Cardiology, Dr. Richard Popp, wrote in a 1998 article that the physical examination of the future will include echocardiography as part of the assessment.

The reliance on analogue videotape in echocardiography has many limitations. Digital echocardiography offers manipulation and display of images not possible with videotape. The ability to view serial studies as well as resting and stress images side-by-side simultaneously is a clear advance. In the setting of coronary artery disease this ability is critical, and in acute myocardial infarction there is improved ability to assess changes in global or regional ventricular function over time. Regional dysfunction is more easily judged with digital echo, and some subtle wall motion abnormalities are best detected with digital echo. Wall motion may be delayed, or the abnormality may occur in diastole rather than systole and is not apparent in real-time imaging. Frame-by-frame or partial cardiac cycle analysis is an advantage when assessing wall motion. Simultaneous viewing of the digital echo and the coronary cineangiogram is a clear advantage.

All ultrasound instruments today have digital output. New software packages permit using the digital output in a convenient, simple fashion. Digital echo is the best technique to look at the damaged myocardial muscle as it best defines the infarct damage. Other complications, such as mitral insufficiency, can be seen in 10-15 seconds at the bedside with digital technology, whereas with videotape 10-15 minutes would be required.