Contrast echocardiography: applications and limitations

Echocardiography is one of the most commonly used noninvasive imaging modalities in cardiology. Its portability, lack of ionizing radiation, excellent temporal and spatial resolution, and low cost make echocardiography an attractive technology. However, a significant proportion of patients have suboptimal images that decrease the diagnostic utility of echocardiography. One method to enhance the assessment of cardiac structure and function involves the administration of microbubble contrast agents. Capitalizing on interactions between microbubbles and ultrasound, imaging modalities that were specifically designed to enhance microbubble signal while suppressing tissue signal have been developed. These modalities can be used for either left ventricular opacification or myocardial perfusion imaging. The current applications of contrast echocardiography, along with the safety and limitations of the technology will be reviewed.     

Contrast echocardiography: An update

Despite the advent of tissue harmonic imaging, echocardiography fails to produce diagnostically useful images in a significant proportion of patients. This often leads to inaccurate assessment of left ventricular function, necessitating the use of other, more expensive and laborious imaging techniques, purely for diagnostic purposes. This has facilitated the development of microbubbles, which together with ultrasound, produce opacification of the left ventricular cavity, thus enabling clear visualization and accurate quantification of left ventricular function. Contrast agents have also facilitated the development of myocardial contrast echocardiography. This allows assessment of cardiac anatomy, function, and perfusion, all in one sitting, by the bedside. Contrast ultrasound imaging also has now been applied to newer techniques (eg, real-time three-dimensional echocardiography) and is also showing promise in other cardiovascular scans (eg, carotid ultrasound for intima-media thickness). Thus, contrast agents play a pivotal role in noninvasive cardiovascular imaging and its use worldwide is likely to increase.     

Improved reliability for echocardiographic measurement of left ventricular volume using harmonic power imaging mode combined with contrast agent

Harmonic power imaging (HPI) is a new echocardiographic modality that enhances the detection of contrast agents in the left ventricle. The endocardium can be delineated by conventional echocardiography using ultrasound contrast agents, although the images tend to be faint. The present study was designed to assess left ventricular volume using HPI after intravenous injection of the contrast agent Levovist (Schering SA, Berlin, Germany) in 25 unselected patients. End-diastolic volume, end-systolic volume, and ejection fraction were determined for each patient with angiography and with 4 different ultrasound modalities: (1) conventional mode without contrast, (2) contrast conventional mode, (3) contrast harmonic intermittent imaging mode, and (4) contrast triggered HPI. The use of HPI improved correlations between the echographic and angiographic measurements for all parameters as well as precision and bias determined by Bland and Altman analysis. The relative errors for interobserver variability were also lower with HPI. This study demonstrates that echocardiographic determination of left ventricular volumes and ejection fraction is more accurate and reproducible using HPI combined with Levovist.     

Current applications of contrast echocardiography

Transthoracic echocardiography is a practical, widely available non-invasive imaging technique examining cardiac structure and function at rest and during stress. However, diagnostically useful images are not provided in a non-negligible proportion of patients, mainly because of obesity and lung disease. The use of echo-contrast agents (microbubbles consisting of high molecular weight gas encapsulated in a outer shell which have ultrasound characteristics distinctly different from those of the surrounding blood cells and heart tissue) solves these issues, providing cardiac chamber opacification and improving endocardial border definition, consequently allowing a more accurate quantification of left ventricular function. Besides improving the assessment of left ventricular function, echo-contrast agents may be used also to assess the myocardial perfusion at the capillary level, providing useful information about myocardial blood flow. Aim of the present paper is to provide an overview of the main clinical applications of contrast echocardiography, i.e. left ventricular opacification and myocardial contrast echocardiography.     

Clinical application and laboratory protocols for performing contrast echocardiography

Technically difficult echocardiographic studies with suboptimal images remain a significant challenge in clinical practice despite advances in imaging technologies over the past decades. Use of microbubble ultrasound contrast for left ventricular opacification and enhancement of endocardial border detection during rest or stress echocardiography has become an essential component of the operation of the modern echocardiography laboratory. Contrast echocardiography has been demonstrated to improve diagnostic accuracy and confidence across a range of indications including quantitative assessment of left ventricular systolic function, wall motion analysis, and left ventricular structural abnormalities. Enhancement of Doppler signals and myocardial contrast echocardiography for perfusion remain off-label uses. Implementation of a contrast protocol is feasible for most laboratories and both physicians and sonographers will require training in contrast specific imaging techniques for optimal use. Previous concerns regarding the safety of contrast agents have since been addressed by more recent data supporting its excellent safety profile and overall cost-effectiveness.     

Role of Contrast Echocardiography for the Assessment of Left Ventricular Function

The endocardial border of the left ventricle is incompletely identified in at least 30% of patients at rest or during stress echocardiography during fundamental imaging. This may lead to inaccurate assessment of regional and global left ventricular function or may lead to further diagnostic imaging with another modality resulting in a higher cost of healthcare. The recent development of second generation ultrasound contrast agents has resulted in improved detection of endocardial border at rest and during stress fundamental echocardiography. This has been consistently shown in various clinical trials involving 702 patients using a new contrast agent, SonoVue™. Other studies with contrast agents have also shown improved accuracy for determining left ventricular ejection fraction and volumes. Although unenhanced tissue harmonic imaging itself improved the assessment of left ventricular function, contrast enhanced harmonic imaging has recently been shown to be more accurate; however, larger clinical studies are required to establish the value of harmonic contrast imaging for the assessment of left ventricular function.     

Usefulness of contrast agents in the diagnosis of left ventricular pseudoaneurysm after acute myocardial infarction.

BACKGROUND AND OBJECTIVE: The diagnosis of left ventricular pseudoaneurysm after acute myocardial infarction is usually based on echocardiography. However, this technique may have limitations in some patients, especially in cases with suboptimal acoustic window. The objective of this study was to evaluate the usefulness of contrast echocardiography in the diagnosis of left ventricular pseudoaneurysm after myocardial infarction. METHODS AND RESULTS: The study population comprises six patients in whom a two-dimensional echocardiography showed an image consistent with left ventricular pseudoaneurysm. Levovist (Schering) 4gr was administered i.v. to more clearly visualize the blood flow from the left ventricle to the left ventricular pseudoaneurysm cavity in all patients. Infarct location was anterior in five patients, and posterolateral in one. No patient had received thrombolysis or primary angioplasty during the acute phase. The transthoracic echocardiographic study showed an echo-free space adjacent to left ventricle in all patients. In four cases, the diagnosis of left ventricular pseudoaneurysm was made before contrast administration. In the remaining two patients, the definite diagnosis was made only after Levovist administration. CONCLUSION: In the diagnosis of postinfarction left ventricular pseudoaneurysm, the administration of contrast agents may be of help in the correct visualization of the blood flow from the left ventricle to the left ventricular pseudoaneurysm cavity, and may allow a definite diagnosis to be obtained in some patients.     

Recent advances in myocardial contrast echocardiography

Myocardial contrast echocardiography (MCE) has undergone many advances in the past several years through remarkable developments in contrast agent and ultrasound equipment technology. Microbubble ultrasound contrast agents can now safely transit the pulmonary circulation to provide opacification of the left ventricular cavity, improved endocardial border definition, and detection of myocardial perfusion. The role of contrast echocardiography in enhancing technically difficult images is now well established in clinical practice, and has proven especially useful in the stress and intensive care unit settings. Major progress has been made in the application of MCE for myocardial perfusion assessment in acute and chronic ischemic heart disease syndromes, and comprises the focus of this review. Advances in novel applications of contrast echocardiography, including targeted delivery of genetic and pharmaceutical materials, have also occurred, but remain in a preclinical phase. In summary, the combination of recent innovations in ultrasound equipment, and microbubble acoustics, allows for exciting exploration of the expanding role of contrast echocardiography in clinical practice.     

The clinical applications of contrast echocardiography.

Ultrasound contrast agents are approved for opacification of the heart chambers and to improve endocardial border definition. The myocardial contrast enhancement is also very useful for assessing thickening of the myocardium and myocardial perfusion. Several multicentre and numerous single-centre trials have demonstrated the usefulness of contrast echocardiography in clinical practice. Contrast echocardiography is probably one of the best validated echocardiographic techniques. Improved accuracy of contrast-enhanced images is not restricted to patients with a poor baseline image quality. Even with an optimal baseline image quality the borders are not as well defined as after LV opacification. Usage of contrast can improve image alignment and helps to avoid off-axis scanning. Contrast studies are particularly useful when a precise measurement of LV function is needed: 1. To decide about the need of implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy (CRT), 2. Follow-up of patients with moderate valvular disease and decision for surgical treatment, 3. Selection and monitoring of patients undergoing chemotherapy with cardiotoxic drugs, 4. Assessment of LV function in patients in intensive care and coronary care units. Optimal endocardial border delineation is crucial and often can be achieved only by ultrasound contrast: 1. Assessment of LV thrombi and masses, 2. Left ventricular non-compaction/apical hypertrophy, 3. Right ventricular dysplasia, right ventricular thrombus, 4. Stress echocardiography and regional wall motion assessment. Future echocardiography will be more 3D and more quantitative than current echocardiography. And contrast echocardiography has already proven its value for both applications.     

Contrast echocardiography: clinical applications and future prospects

BACKGROUND: Contrast echocardiography has been used as a clinical method for more than 20 years. Using conventional ultrasound techniques the clinical use of contrast was limited. Now the development of "contrast specific" imaging modalities has increased the indications for contrast echocardiography. CONTRAST AGENTS: For clinical use two classes of contrast agents are available: 1. "right heart" contrast media (Echovist, agitated solutions), which do not cross the pulmonary vascular bed following intravenous injection and which can be used with conventional (fundamental) imaging methods, 2. "left heart" contrast media (Levovist, Optison, SonoVue) which need "contrast specific" imaging modalities for optimal use. INDICATIONS: Despite of the developments in Doppler methods and transesophageal echocardiography "right heart" contrast media still are needed in some patients with atrial and pulmonary shunts, complex congenital heart disease, noisy Doppler recordings of tricuspid regurgitation. For "left heart" contrast media improvement of endocardial border definition is the most important indication, which has been validated in a series of well performed studies. Therefore contrast enhanced recordings are recommended in the clinical echo laboratory when unenhanced recordings are suboptimal. Coronary flow reserve of the LAD can be measured using contrast enhanced Doppler echocardiography. All contrast specific imaging modalities provide assessment of myocardial perfusion. The previously used imaging modalities (Harmonic B mode, Pulse Inversion and Harmonic Power Doppler) did not provide sufficient myocardial contrast signals using real-time imaging. Although intermittent imaging resulted in good myocardial opacification, this modality did not gain wider clinical acceptance. NEW TECHNOLOGIES: Using new contrast specific imaging technologies like Power Pulse Inversion, Power Modulation and Coherent Imaging myocardial perfusion can be evaluated in "real-time". Thus simultaneous assessment of left ventricular wall motion and myocardial perfusion became a reality and facilitated the data acquisition. New ultrasound contrast media like SonoVue can be used for all imaging modalities. Recent studies have demonstrated that the information derived from myocardial contrast echocardiography provides clinically relevant information on top of the findings obtained from conventional left ventricular wall motion analysis.     

Myocardial perfusion by contrast echocardiography: diagnosis of coronary artery disease using contrast-enhanced stress echocardiography and assessment of coronary anatomy and flow reserve

The advent of intravenous contrast agents, and newer ultrasound technology to enhance their detection, promises to improve and augment our conventional stress echocardiographic practice by improving diagnostic accuracy and providing novel information regarding myocardial perfusion and functional assessment of the coronary vasculature. The combination of intravenous contrast and harmonic stress echocardiography is a powerful tool for improved wall motion analysis through enhanced image quality, routinely permitting the evaluation of patients with suboptimal images. In this era of cost containment, we await studies in large populations addressing resource utilization and cost-effectiveness to determine if, indeed, all patients presenting with stress echocardiography should receive contrast. Myocardial perfusion can be observed using the technique, but the complex interactions of microbubbles and ultrasound in patients must be understood more fully before its implementation becomes routine practice. Non-invasive imaging of coronary arteries using contrast-enhanced transthoracic harmonic echo/Doppler promises to expand the field of diagnostic and experimental echocardiography, bringing new insight into the pathophysiology of ischemic and non-ischemic heart disease. The continued development of newer contrast agents and refinement of ultrasound imaging equipment ensures that the applications of contrast echocardiography in the assessment of CAD will continue to increase.     

The value of contrast in stress echocardiography

Stress echocardiography is a well validated method of diagnosing myocardial ischaemia and viability. Its limitations are also well known, related to a subjective interpretation and lack of reproducibility. One of the solutions suggested to improve its diagnostic performance is the use of ultrasonic contrast agents which presents many advantages. In difficult patients, the left ventricular chamber may be opacified, both at rest and at peak effort with a significant improvement in the detection of the endocardial contour and in the reproducibility of the interpretation of the images. The diagnostic performance of stress echocardiography with contrast is less dependent on the conditions of observation. In addition, recent technical advances enable the same ultrasonic contrast agents to be used for the study of myocardial perfusion. The first clinical studies using these techniques report the feasibility of simultaneous analysis of wall motion abnormalities and myocardial perfusion on exercise. Further progress is expected to facilitate the interpretation and quantification of these investigations which should further increase the diagnostic value of stress echocardiography.     

Dual-frame image-freezing unit for two-dimensional echocardiography. Preliminary clinical report

We developed a "dual-frame image-freezing unit", which enables acquisition of two stop-frame images of the two-dimensional echocardiogram at different points within one cardiac cycle. We assessed the clinical usefulness of this unit by estimating the left ventricular ejection fraction with apical biplane two-dimensional echocardiography in 25 patients who underwent left ventricular biplane cineangiography. The unit functioned successfully in all instances. It was much easier to obtain the left ventricular end-diastolic and end-systolic echocardiographic images than to obtain such images using conventional videotape play-back. The quality of the images obtained by this unit was better than those obtained from videotape play-back. The echocardiographic estimates of the left ventricular ejection fraction showed an excellent correlation with estimates obtained by contrast left ventricular cineangiography. We conclude that this dual-frame image-freezing unit can be satisfactorily applied for the assessment of the left ventricular ejection fraction by two-dimensional echocardiography.     

Improvement in Endocardial Border Delineation Using Tissue Harmonic Imaging

Background and Methods: For years, tissue has been assumed to be a linear medium in diagnostic ultrasound applications; thus, no backscattered signals in the second harmonic band are expected in harmonic imaging without the injection of a contrast agent. However, it has been shown that a useful tissue image is formed even without a contrast agent. The aim of this study was to evaluate whether this tissue harmonic image provided improved visualization of endocardial borders. Fifty-six adult patients with various heart diseases were investigated using conventional two-dimensional echocardiography and tissue harmonic imaging. In 30 of these patients, the left ventricular endocardial borders were well defined in the standard parasternal and apical views using conventional two-dimensional echocardiography. In the remaining 26 patients, delineation of endocardial borders was not possible in at least two segments. The equipment used was an ATL HDI-3000 diagnostic system equipped with harmonic imaging. Results: In all 56 patients, the myocardium and valves could be imaged with tissue harmonic imaging. Harmonic recordings were sharper and contained fewer clutter artifacts than conventional recordings. Most striking was the enhancement of left ventricular endocardial borders. In the 26 patients with incomplete delineation of left ventricular endocardial borders, wall motion could be evaluated in 290 of 312 (93%) segments with tissue harmonic imaging compared with only 168 of 312 (54%) segments with conventional echocardiography (P < 0.001). Conclusions: Tissue harmonic imaging improves image quality and can be used to enhance the definition of left ventricular endocardial borders. These findings can be explained by the nonlinear propagation of ultrasound within the tissue, which results in distortion of the transmitted signal and, thus, harmonic generation.     

Freehand three-dimensional assessment of left ventricular volumes and ejection fraction with ultrasound contrast agent LK565.

AIMS: Accurate assessment of left ventricular function by determining left ventricular volumes and ejection fraction is important in evaluating the prognoses of patients with heart failure. Two-dimensional (2D) echocardiography suffers from low correlation with reference methods like ventriculography. Three-dimensionally (3D) assessed data have been proved to have better conformity. Endocardial border delineation remains a problem, however, especially in patients with suboptimal recordings. Few data exist on 3D-echocardiographic volumetry with ultrasound contrast agents (UCAs). We evaluated the second-generation UCA LK565 for its boundary-tracing capacities in freehand 3D echocardiography in a phase II clinical trial. Safety and efficacy of the novel contrast agent were also evaluated. METHODS AND RESULTS: Forty patients between the age of 42 and 77 were included in this trial. Left ventricular end-systolic and -diastolic volume (LVESV, LVEDV) and ejection fraction (EF) were determined by either 2D or 3D freehand second harmonic echocardiography with and without use of LK565. Parameters were compared statistically with ventriculography performed in 35 patients. Immune response to LK565 was evaluated by analysing phagocytosis capacity and kinetics of inflammatory cytokines (TNF-alpha, IL-4, IL-10, IFN-gamma). Patients were monitored for adverse events up to 72 h after application of the UCA. Calculated values for left ventricular volumes and ejection fraction correlated best for freehand 3D echocardiography in combination with LK565 (r=0.92 for LVEDV; r=0.96 for LVESV; r=0.94 for EF). Excellent left ventricular contrast enhancement was achieved for approximately 8 min. A reversible saturation of phagocytosis capacity for monocytes and neutrophils set in with a maximum peak at 6h. No significant increase in cytokine expression was observed. CONCLUSION: LK565 improves feasibility of endocardial border delineation in 3D echocardiography, leading to better correlation of left ventricular volumetry with reference methods. Efficacy and safety of LK565 are equivalent to those of conventional UCAs.     

Safety of ultrasound contrast agents in stress echocardiography

Definity and Optison are perflutren-based ultrasound contrast agents used in echocardiography. United States Food and Drug Administration warnings regarding serious cardiopulmonary reactions and death after Definity administration highlighted the limited safety data in patients who undergo contrast stress echocardiography. From 1998 and 2007, 2,022 patients underwent dobutamine stress echocardiography and 2,764 underwent exercise stress echocardiography with contrast at the Cleveland Clinic. The echocardiographic database, patient records, and the Social Security Death Index were reviewed for the timing and cause of death, severe adverse events, arrhythmias, and symptoms. Complication rates for contrast dobutamine stress echocardiography and exercise stress echocardiography were compared with those in a control group of 5,012 patients matched for test year and type who did not receive contrast. Ninety-five percent of studies were performed in outpatients. There were no differences in the rates of severe adverse events (0.19% vs 0.17%, p = 0.7), death within 24 hours (0% vs 0.04%, p = 0.1), cardiac arrest (0.04% vs 0.04%, p = 0.96), and sustained ventricular tachycardia (0.2% vs 0.1%, p = 0.32) between patients receiving and not receiving intravenous contrast, respectively. In conclusion, severe adverse reactions to intravenous contrast agents during stress echocardiography are uncommon. Contrast use does not add to the baseline risk for severe adverse events in patients who undergo stress echocardiography.     

Real-time three-dimensional echocardiography for improved evaluation of diastolic function using volume-time curves

BACKGROUND: Accurate assessment of left ventricular function is of the greatest importance in clinical cardiology for decision making. Diastolic dysfunction is getting more concern as a cause of heart failure while, currently used non-invasive modalities for diagnosing diastolic abnormalities have significant limitations. Dynamic left ventricular volume change was applied for the evaluation of diastolic function by various techniques that have been demonstrated to be of diagnostic value. However, it has not been accepted into clinical practice because existing techniques are either invasive, inaccurate, expensive or time consuming. REAL-TIME THREE-DIMENSIONAL ECHOCARDIOGRAPHY: Real-time three-dimensional (3-D) echocardiography is a new ultrasound technique that provides transthoracic volumetric images of the heart in real time. Thereby, the acquired images are ideally suited for the assessment of dynamic left ventricular volume change. Generation and analysis of left ventricular volume-time curves by real-time 3-D echocardiography has been demonstrated to be feasible in normal subjects and patients and accuracy of volume-time curves was good compared to magnetic resonance imaging. We compare the new real-time 3-D echo approach with the advantages and limitations of existing noninvasive and invasive techniques.     

Reproducibility of stress echocardiography using intravenous injection of ultrasound contrast agent (by 963)

Despite the widespread use of stress echocardiography, its reproducibility is still limited by high interobserver variability. Therefore, the purpose of the present study was to improve the reproducibility of a stress (exercise) echocardiography using a new transpulmonary ultrasound agent (BY 963). Stress echocardiography was performed in 12 healthy volunteers with suboptimal endocardial border delineation during exercise echocardiography. A special 45° lateral tilted bike stress echocardiography table was used for exercise testing. Echocardiographic images were recorded on-line at rest and during exercise on a video tape and additionally digitized on-line on a stress echo computer. End-diastolic (EDVml), end-systolic (ESVml) volume and ejection fraction (EF%) were estimated in the 4-chamber view. The measurements were performed before and after injection of 2.5 ml and 5 ml BY963 at rest and in maximal exercise. A new contrast agent (BY 963) leads to a sufficient contrast effect for the left ventricular cavity after intravenous administration and permits a good delineation of left the endocardial border. The interobserver variability was determined using blinded investigation by two observers. The correlation of EDV and ESV determination at rest was r = 0.68/0.33, after 2.5 ml BY 963 r = 0.97/0.93 and after 5 ml BY 963 r = 0.90/0.93. The correlation for EDV and ESV during exercise was r = 0.52/0.33, after 2.5 ml BY 963 r = 0.88/0.80 and after 5 ml BY 963 r = 0.95/0.92. At rest mean EF without contrast was 61 ± 6%/67 ± 7% (r = 0. 130), after 2.5 ml BY 963 i.v. 69 ± 8%/72 ± 7% (r = 0.82) and after 5 ml BY 963 i.v. 73 ± 8%/73 ± 8% (r = 0.98%) respectively. In exercise, mean EF without contrast was 68 ± 8%/70 ± 6 (r = 0.013), after 2.5 ml BY 963 83 ± 6%/81 ± 5 and after 5 ml 83 ± 4%/82 ± 3 (r = 0.86). Summary: The estimation of the end-systolic volume in exercise will be improved significantly and the estimated EF values will be higher compared to EF values obtained without contrast application. Transpulmonary contrast echocardiography for analysis of left ventricular volumes and ejection fraction can be routinely used in stress echocardiography. Intravenous administration of BY 963 improves the reproducibility of quantitative analysis of left ventricular function in healthy volunteers. Further studies in patients with cardiac diseases are required to corroborate this observation.     

Pulmonary transit of echocontrast agents during mechanical ventilation: a clinical transthoracic echocardiographic study

In this study, we investigated whether the ultrasound contrast agents Levovist or Sono Vue injected intravenously during mechanical ventilation effectively pass through the pulmonary circulation. With echocardiography, we measured the time for the contrast to pass through the lungs; and the intensity of right and left ventricular cavity opacification at four time points: during spontaneous breathing (baseline), 5 minutes after the beginning of mechanical ventilation, and 5 minutes and 30 minutes after extubation. Forty patients undergoing elective peripheral neurosurgical procedures were prospectively and randomly enrolled: 20 patients received intravenous Levovist 1 g and 20 patients received intravenous Sono Vue 1 mL, at the four predefined time points. After intravenous injection, both Levovist and Sono Vue effectively passed through the lungs and opacified the right and left ventricular cavities, at the four time points. Pulmonary transit times were similar and constant for the two contrast agents tested: 6 +/- 2 seconds at baseline, 5 +/- 2 seconds during mechanical ventilation, 7 +/- 2 seconds at 5 minutes and 6 +/- 2 seconds at 30 minutes after extubation with Levovist; and 6 +/- 4 seconds at baseline, 6 +/- 3 seconds during mechanical ventilation, 6 +/- 2 seconds at 5 minutes and 7 +/- 3 seconds at 30 minutes after extubation with Sono Vue. In all patients, each of the four contrast injections achieved high-grade right and left ventricular chamber opacification. In conclusion, both the ultrasound contrast agents tested in this study, Levovist and Sono Vue, after intravenous injection pass through the pulmonary circulation during mechanical ventilation. Ultrasound contrast agents with these characteristics are suitable for intraoperative organ perfusion studies, with intravenous injection.     

Intravenous contrast echocardiography

Intravenous contrast echocardiography has become possible in Japan because of the release of the commercially available contrast agent, Levovist. Intravenous administration of Levovist satisfactorily stains the left ventricular cavity, which makes it possible to clearly delineate the endocardial border. Clear delineation of the endocardial border provides easy and accurate measurement of left ventricular dimension and wall thickness, and wall motion abnormalities can be easily and accurately judged, too. Another benefit of intravenous contrast echocardiography is the assessment of myocardial perfusion. Our preliminary experimental and clinical experiences showed the possibility of myocardial staining with intravenous contrast echocardiography. Impressive myocardial staining is obtainable with the combined use of intermittent and contrast harmonic power Doppler imaging. In order to obtain reproducible and clear myocardial contrast images, we have to pay attention to how to inject contrast and settings of ultrasound equipment, i.e., mechanical index, gain setting, depth of focus point, and pulse repetition frequency, artifacts. In the near future, a lot of issues should be standardized to make it possible to compare myocardial contrast echo studies.