Clinical Experience with SonoVue in Myocardial Perfusion Imaging

Ultrasound-enhancing agents have the potential to evaluate myocardial perfusion, adding a new dimension to echocardiography. This article summarizes the clinical studies involving SonoVue, a new intravenous ultrasound contrast agent, in assessing myocardial perfusion. Safe and well tolerated, SonoVue coupled with echocardiography has the capability to identify perfusion abnormalities, as confirmed by scintigraphic imaging. While the optimal modalities for ultrasound perfusion assessment are not yet determined, numerous technical advances have been introduced: continuous infusion or slow intravenous administration of the agent, harmonic intermittent imaging, pulse inversion, background subtraction, color coding, and others. SonoVue is a promising new agent in the booming field of myocardial contrast echocardiography.     

Subendocardial Steal Effect Seen with Real-Time Perfusion Imaging at Low Emission Power during Adenosine Stress: Replenishment M-Mode Processing Allows Visualization of Vertical Steal

We present a patient in whom power pulse inversion imaging clearly demonstrated a subendocardial myocardial perfusion defect during contrast vasodilator stress using adenosine. The defect was best appreciated with M-mode postprocessing of power pulse inversion imaging data.     

Bulls-Eye Display and Quantitation of Myocardial Perfusion Defects Using Three-Dimensional Contrast Echocardiography

Three-dimensional (3-D) myocardial contrast echocardiography (MCE) is able to derive parallel cutting planes of the left ventricle (LV). However, assessment of the site and extent of myocardial perfusion abnormalities has to rely on the reader's 3-D mental reconstruction from the tomograms, and a manual approach has to be employed for quantitative analysis. The objective of this study was to explore the display and quantitative capability of a bulls-eye format from contrast 3-D MCE in the assessment of perfusion abnormalities derived from a canine model of acute myocardial infarction (MI). Three-dimensional MCE data were acquired sequentially in a rotational scanning format during triggered harmonic imaging with an intravenous contrast agent. Reconstructed short-axis views of the LV were aligned in a bulls-eye format with the apex as the inner most ring. The total LV was divided into 120 sectors. The number of sectors with lack of contrast enhancement was used to derive the percent of the LV (%LV) with perfusion defect and was compared with the extent of MI calculated from postmortem triphenyl tetrazolium chloride (TTC) staining. The perfusion defect regions shown on bulls-eye images corresponded correctly with the territories of the occluded coronary arteries. Three-dimensional MCE perfusion defect mass (19.2 +/- 6.0 %LV) correlated well with anatomic MI mass (19.3 +/- 5.6 %LV; r = 0.92, SEE = 2.3%, mean differential = 0.1 +/- 2.4%). We conclude that bulls-eye display of contrast 3-D MCE demonstrates the site and extent of perfusion abnormalities in an easily appreciable manner. It also allows fast and accurate assessment of endangered myocardium.     

Myocardial Contrast Echocardiography: Clinical Benefit and Practical Issues

Real-time bedside evaluation of myocardial perfusion after intravenous application of micro-bubbles is the ultimate goal for contrast echocardiography. Over the past decade rapid evolution has occurred in the development of contrast agents, ultrasound equipment tailored to their detection, and image interpretation. This article offers a review of the basic concepts of the technique's background, contrast agent design, and imaging technology. The major clinical indications of myocardial contrast echocardiography are evaluation of acute ischemic syndromes, diagnosis of viable myocardium following AMI, and the detection of CAD using stress contrast perfusion imaging. Furthermore, the article addresses the most significant practical problems and suggested solutions to master those problems. As major new achievements are realistic expectations for the first decade of the twenty-first century, we conclude that the coupling of a new generation of contrast agents with innovative echocardiographic instrumentation will ultimately enable the full potential of myocardial contrast echocardiography to be realized which may revolutionize modern echocardiography.     

Myocardial Perfusion Abnormalities by Intravenous Administration of the Contrast Agent NC100100 in an Experimental Model of Coronary Artery Thrombosis and Reperfusion

The aim of this study was to evaluate a second-generation echo contrast agent (NC100100) for the study of myocardial perfusion. In eight anesthetized open-chest dogs, this agent was injected intravenously under baseline conditions, during acute coronary thrombosis, and after reperfusion, using both fundamental (FI) and harmonic (HI) imaging, both continuous and intermittent imaging, and both ultrasound (US) and integrated backscatter (IBS) imaging. Contrast injections did not modify the hemodynamic parameters. With all imaging modalities, myocardial contrast enhancement (MCE) was higher with intermittent than with continuous imaging (134 vs 82 gray level/pixel using FI, P = 0.02; 62 vs 32 acoustic units using US HI, P = 0.02; and 52 vs 12 dB using IBS, P = 0.05). MCE equally increased using either US or IBS imaging. The accuracy of MCE in detecting perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis was very good (sensitivity and specificity = 93% and 95% and 89% and 93%, respectively). The extent of myocardial perfusion defects by echo contrast showed a closer correlation with microspheres using HI (r = 0.82) than FI (r = 0.53). Thus, the intravenous administration of NC100100 during intermittent HI allows myocardial perfusion abnormalities to be accurately detected during acute myocardial infarction.     

Stimulated Acoustic Emission Nonbackscatter Contrast Effect of Microbubbles Seen with Harmonic Power Doppler Imaging

Transient imaging has been introduced to enhance the signal intensities when using echo contrast agents. However, this phenomenon is not clearly understood. To evaluate the mechanisms of this phenomenon, isolated pig hearts were investigated with different echo imaging techniques in the beating, working heart as well as in an asystolic state without any motion of the heart. The hearts of five German farm pigs (21 ± 2.5 kg) were surgically explanted and inserted in an artificial circulation providing physiological flow and pressures. Levovist in the dosage of 0.05–0.3 g was injected into the left atrium and contrast effects evaluated in the left ventricular (LV) cavity and in the myocardium with an ultrasound imager (ATL, HDI 3000) equipped with a prototype software for harmonic imaging. Harmonic B-scans and power Doppler registrations were performed with continuous and intermittent recordings (ECG triggered at end-systole) in the beating heart and using an external trigger in the asystolic heart in which perfusion was interrupted for 20 seconds. In the beating pig heart, transient harmonic power Doppler imaging provided intensive opacification of the LV cavity and visible myocardial uptake when ECG triggering was performed. In the asystolic pig heart, with uninterrupted perfusion, both triggered and nontriggered registrations showed contrast signals in the LV cavity and in the myocardium. These findings cannot be explained with the known physics of ultrasound contrast media. Stimulated acoustic emission occurring during disintegration of the microbubbles in the acoustic field would explain this phenomenon, which has not yet been described for Levovist.     

Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results

Background: In fundamental and second harmonic echocardiography new contrast media opacify the cavities and reduce the difference in the gray level between the cavity and the myocardium thus obscuring the borders of the myocardium. Objectives: The aim of the study was to examine the potential usefulness of second harmonic power Doppler imaging (HPD) in providing adequate delineation of the myocardium from the left ventricular (LV) and right ventricular (RV) cavities during intravenous contrast echocardiography. Using HPD, microbubbles in a cavity or a tissue are imaged as colored pixels superimposed on a conventional B-scan image. Methods: In a pilot study, three healthy volunteers and two patients with ischemic heart disease were investigated using an ATL-HDI 3000 echo system. Four chamber views were obtained using fundamental B-scan, harmonic B-scan two-dimensional echocardiography (H2D) and HPD following intravenous injections of 3 g Levovist*. Results: Using intermittent scanning/recording, H2D and HPD provided intensive and homogenous contrast effects in the RV and LV cavities. Good delineation of the myocardium was found in all subjects using HPD, whereas in two of three volunteers and in one of two patients ventricular septal and apical endocardial borders were obscured during H2D. No obvious change in myocardial backscatter was visually found with H2D. However, in all three healthy volunteers and in one of two patients, HPD recordings demonstrated patchy and reticular patterns in the myocardium, which were different from the homogenous signals in the LV cavity. These are consistent with imaging of intramyo-cardial coronary vessels. Conclusions: HPD with intravenous Levovist is feasible. This technique demonstrated good delineation of ventricular cavities from the myocardium as well as presence of visible contrast in the myocardium. This pilot study justifies further clinical trials to evaluate the clinical benefit of this approach.     

Harmonic Power Doppler Contrast Echocardiography: Preliminary Experimental Results

This preliminary experimental study demonstrates the potential usefulness of harmonic power Doppler imaging in producing left ventricular myocardial opacification and demonstrating intra-myocardial coronary vessels during contrast echocardiography using Levovist, a saccharide-based contrast agent. The contrast effect was most dramatic when a vasodilator such as dipyridamole or nitroglycerin was used in conjunction with contrast injections of Levovist. No significant myocardial opacification was noted with B-mode harmonic imaging alone.     

Correlation between Myocardial Dysfunction and Perfusion Impairment in Diabetic Rats with Velocity Vector Imaging and Myocardial Contrast Echocardiography

The purpose of this study was to investigate whether myocardial systolic dysfunction and perfusion impairment occur in diabetic rats, and to assess their relationship using velocity vector imaging (VVI) and myocardial contrast echocardiography (MCE). Forty‐six rats were randomly divided into either control or the diabetes mellitus (DM) groups. DM was induced by intraperitoneal administration of streptozotocin. Twelve weeks later, 39 survival rats underwent VVI and MCE in short‐axis view at the middle level of the left ventricle, both at rest and after dipyridamole stress. VVI‐derived contractile parameters included peak systolic velocity (V_s), circumferential strain (ε_c), strain rate (SR_c), and their reserves. MCE‐derived perfusion parameters consisted of myocardial blood flow (MBF) and myocardial flow reserve (MFR). At rest, SR_c in the DM group was significantly lower than in the control group, V_s, ε_c, and MBF did not differ significantly between groups. After dipyridamole stress, all VVI parameters and their reserves in the DM group were significantly lower than those in the control group, MBF and MFR were substantially lower than those in the control group, too. Meanwhile, significant correlations between VVI parameter reserves and MFR were observed in the DM group. Both myocardial systolic function and perfusion were impaired in DM rats. Decreased MFR could be an important contributor to the reduction in myocardial contractile reserve.     

Identification of Perfusion Abnormalities Using FSO69, a Novel Contrast Agent, in Conscious Dogs

Recent advances in the production of echocardiographic contrast agents has resulted in the ability to delineate areas of hypoperfusion after coronary occlusions and stenoses following their intravenous injection. Most of these studies though have been done in open chest animals. This study was done to determine if we could assess myocardial perfusion following the intravenous administration of FSO69, a suspension of perfluoropropane filled albumin microspheres (3.6 μm average microbubble size, concentration 8 × 10⁸), in spontaneously breathing closed chest dogs. Twenty-seven mongrel dogs were instrumented on day 1. The chest was then closed and the dogs were restudied 3–7 days later, while spontaneously breathing. Homogeneous perfusion was observed in most dogs by all three independent and blinded observers. Perfusion abnormalities were likewise identified in most instances by all blinded reviewers on interventions designed to decrease regional blood flow. A good correlation between perfusion defect size between investigators was observed. In summary, our data suggest that FSO69 can be used to assess regional myocardial perfusion in spontaneously breathing dogs. These results support its use in humans.     

负荷心肌灌注显像在心肌桥临床应用中的研究进展

负荷心肌灌注显像通过检测核素在心肌的分布,明确心肌缺血的部位和程度,因此,它能够评价冠状动脉心肌桥是否影响心肌供血及影响程度。负荷心肌灌注显像具有敏感性及特异性较高,且相对价廉、安全无创等优点,在评价心肌桥导致的心肌缺血及缺血的程度范围、判断预后及指导下一步治疗中具有重要的临床价值及应用前景。     

Optimal Use of Contrast Echo in Daily Practice: What Do We Need?

With new low power imaging and contrast application technology, it seems possible for the first time to develop a protocol that combines acquisition of both function and perfusion data using a simple modality. For this purpose a European network has been created and this group is currently developing a protocol using a commercially available ultrasound scanner and the infusion of the echocontrast agent SonoVue^® (Bracco). This study describes the technical developments that will promote a comprehensive clinical contrast protocol for assessment of patients with ischemic heart disease. (ECHOCARDIOGRAPHY, Volume 20, Supplement 1, 2003)     

Myocardial Contrast Echocardiography in Assessment of Stable Coronary Artery Disease at Intermediate Dobutamine-Induced Stress Level

Background: Myocardial contrast stress echocardiography (stress MCE) is a novel method for diagnosing coronary artery disease (CAD). Few studies have compared the diagnosis of ischemia by stress MCE to angiographic CAD. Methods: Dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 37 patients (8 women) aged 45–75 years with symptomatic CAD and at least one significant coronary artery stenosis measured by quantitative coronary angiography (QCA). The total and regional perfusion and wall motion (WM) were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 17-segment left ventricular model. Results: An intermediate stress level was obtained in 29 (78%) patients, and 2 (5%) patients obtained peak stress. A perfusion defect was detected in 92% and WM abnormality in 57% of the patients at peak stress (P < 0.01). By perfusion, 70% of stenoses were both detected and correctly anatomically located, compared to 42% by WM (P < 0.01). All 21 patients with multivessel disease and/or proximal left anterior descending (LAD) stenosis measured by QCA were identified by stress-induced perfusion defects, while only 11 of them were identified by WM abnormalities (P < 0.01). Conclusion: Perfusion scoring is superior to WM scoring during stress MCE for diagnosing significant CAD in patients obtaining intermediate stress level, in particular, when multivessel disease or proximal LAD stenosis is present.     

Real-time perfusion imaging: a new echocardiographic technique for simultaneous evaluation of myocardial perfusion and contraction

Myocardial contrast echocardiography (MCE) with high acoustic energy and triggered harmonic imaging is the best established ultrasound technique to date for the assessment of myocardial perfusion. With this technique, however, the ultimate goal of MCE (noninvasive real-time simultaneous assessment of myocardial perfusion and function after an intravenous injection of microbubbles) is not met. Recently, technologic advances have enabled myocardial opacification to be visualized during low-energy real-time imaging. During real-time perfusion imaging, wall motion and myocardial perfusion may be assessed simultaneously, obviating the need of the presently time-consuming combination of different imaging modalities. When high-energy ultrasound bursts are periodically transmitted to produce bubble destruction during low-power imaging, the consecutive frames after destruction delineate the restoration of contrast intensity. Microbubble replenishment rate and peak intensity may be determined subsequently, and provide reliable quantitative parameters of regional microcirculatory flow. This review will introduce the modalities used for real-time perfusion imaging with focus on power pulse inversion imaging and quantitative analysis. Furthermore, we will describe the clinical role the technique may have in the identification of coronary artery disease, quantification of coronary stenosis severity, assessment of myocardial viability, determination of infarction size, and evaluation of reflow and no- or low-reflow after acute myocardial infarction.     

Comparison of Indicator‐Dilution Curves Obtained from Dye Dilution and Echo Contrast Using Harmonic Power Doppler Imaging

BACKGROUND: Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. METHODS AND RESULTS: A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. CONCLUSIONS: We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.     

Myocardial Contrast Echocardiography: Texture Analysis for Identification of Nonperfused versus Perfused Myocardium

This study examined texture analysis for objective identification of nonperfused myocardial segments in myocardial contrast echocardiographic (MCE) images. Short-axis MCE images from six open chest pigs after coronary artery ligation were examined. Six of 26 features (low gray level run emphasis, high gray level run emphasis, sum mean, sum variance, coefficient of variance and diagonal variance) demonstrated a significant texture value difference (P < 0.01) between the nonperfused and perfused segments with minimal statistical distribution overlap between the two groups. This study demonstrates that texture features other than mean gray level can objectively distinguish nonperfused from perfused myocardium in MCE images and may thus augment the diagnostic accuracy of current analysis techniques.