Echocardiographic contrast agents: effect of microbubbles and carrier solutions on left ventricular contractility.

Recently, there has been a resurgence of interest in the use of contrast-enhanced echocardiography as a means of noninvasively assessing myocardial perfusion. However, if injections of echocardiographic contrast agents are to be used for this purpose it is essential that they are not intrinsically toxic to the heart. In this study, the left ventricular end-systolic wall stress-rate-corrected velocity of fiber shortening relation, a load independent index of contractility, was studied in nine dogs. Two-dimensional and targeted M-mode echocardiographic as well as central aortic pressure tracings were made during echocardiographically gated, pressure- and volume-controlled aortic root injections of nonsonicated and sonicated Renografin-76, saline and dextrose 70% (n = 6), and sonicated and hand-agitated Renografin-76/saline mixture (n = 5). Two of nine dogs received all agents. Off-line computer videodensitometric analysis documented myocardial perfusion. In all cases, data were obtained at control and 5 and 15 seconds after injection. Additional data were collected at 25 seconds after injection for the Renografin-76/saline mixture. Alterations in contractility were measured relative to control as changes in rate-corrected velocity of fiber shortening after afterload (measured as end-systolic wall stress) was eliminated as a confounding variable. Under no condition did saline or Renografin-76 cause alterations in left ventricular contractility. Nonsonicated and sonicated dextrose 70% increased left ventricular contractility at 15 seconds but not at 5 seconds after injection. Hand-agitated Renografin-76/saline mixture induced a negative inotropic effect at 5 and 15 seconds after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast echocardiography for evaluation of myocardial perfusion: effects of coronary angioplasty.

Assessment of viable myocardium before and after interventional therapy has become a critical issue in modern cardiology. This report describes a new contrast echocardiographic technique using conventional two-dimensional imaging during direct intracoronary injections of small volumes (1.5 to 2.0 cc) of sonicated Renografin-76. Contrast echocardiography was performed before and after coronary angioplasty in seven patients with single vessel coronary artery disease. Before angioplasty a contrast (that is, perfusion) defect was noted in all seven patients. This defect correlated with the anatomic distribution of the epicardial coronary stenosis. After angioplasty the mean gradient across the stenotic lesion decreased from 52 +/- 11 to 13 +/- 14 mm Hg (p less than 0.01) in association with a fall in the mean diameter of the lesion from 84 +/- 8 to 29 +/- 13% (p less than 0.001). Increased myocardial perfusion to the area of "contrast defect" was demonstrated in only five of the seven patients, despite hemodynamically and angiographically successful angioplasty. Thus, contrast echocardiographic techniques performed during interventional therapy and used in conjunction with standard coronary angiographic procedures may provide additional physiologic information regarding regional myocardial perfusion after attempts at revascularization.

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies.

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue-type plasminogen activator therapy versus primary coronary angioplasty: impact on myocardial tissue perfusion and regional function 1 month after uncomplicated myocardial infarction.

OBJECTIVES: This study sought to compare the impact of primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction (AMI) on 1-month infarct size and microvascular perfusion. BACKGROUND: The effect of the reperfusion strategies of primary coronary angioplasty and thrombolytic therapy on microvascular integrity still remains to be determined. METHODS: Sixty-two consecutive patients with a first AMI, undergoing intravenous tissue-type plasminogen activator (t-PA) therapy (32 patients, Group I) or primary angioplasty (30 patients, Group II), were studied. Only patients with 1-month Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 were selected for the study. Patients in whom primary angioplasty was unsuccessful or those with clinical evidence of failed reperfusion were excluded. Microvascular perfusion was assessed at 1 month by intracoronary injection of sonicated microbubbles. Contrast score index (CSI) and wall motion score index (WMSI) were derived using qualitative methods. RESULTS: At baseline there were no significant differences between groups for age, risk factors, time to hospital presentation, Killip class on admission, prevalence of multivessel disease or anterior infarct site, infarct area extension before reperfusion, peak creatine kinase levels and postinfarction treatment. Conversely, significant differences between groups were found at follow-up for percent residual infarct related-artery (IRA) stenosis (70 +/- 12 vs 36 +/- 14 [mean +/- SD], p = 0.0001), CSI (1.02 +/- 0.4 vs. 1.49 +/- 0.5, p = 0.0003) and WMSI (1.67 +/- 0.3 vs. 1.45 +/- 0.3, p = 0.015). In particular, in the subset of patients with TIMI grade 3 flow, a perfusion defect occurred in one or more segments subtended by the IRA in 72% of Group I versus 31% of Group II patients (p < 0.00001) and in 27% of Group I versus 8% of Group II segments (p < 0.00001). CONCLUSIONS: The present study shows, in a highly selected cohort with successful IRA recanalization, that primary angioplasty is more effective than thrombolysis in preserving microvascular flow and preventing extension of myocardial damage at 1-month after AMI.

Microbubble dynamics visualized in the intact capillary circulation.

The potential for the use of contrast echocardiography to study myocardial perfusion has generated efforts to develop standardized echo contrast agents. The two methods used in this laboratory to generate microbubbles in solutions serving as contrast agents included the widely used hand-agitation method and the newer ultrasonic microcavitation (sonication) method. The latter has been demonstrated to generate smaller and more uniform microbubbles in an in vitro system. The present study was designed to observe, by direct microscopic examination of a cat mesentery preparation, the behavior and fate of the microbubbles in an in vivo system. The in vivo mesentery observations confirm the critical role of microbubble size in its unhindered passage through the capillary vasculature. The smaller and more uniform sonicated microbubbles passed rapidly through the microcirculation along with the red blood cells, whereas the larger microbubbles were observed to coalesce and interrupt the flow of blood and subsequently collapse or shrink.

Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents.

To facilitate the passage of echo contrast agents through the microcirculation and the echocardiographic study of myocardial perfusion, ultrasonic energy (sonication) was employed to produce contrast agents consisting of relatively uniform, stable and small (less than 10 mu diameter) gaseous microbubbles suspended in liquid solutions. The size and persistence of the microbubbles was verified by light microscopy and an in vitro system were employed for comparative assessment of peak echo amplitude and echo persistence characteristics of various contrast agents. The study indicated that although a variety of hand-agitated and sonicated contrast agents provided satisfactory echo intensities, sonication was clearly superior to the hand-agitation method, because sonication produced smaller, more uniform and more stable microbubbles that may be suitable for myocardial contrast echocardiography. It is concluded that of the contrast agents examined, sonicated solutions of sorbitol (70%) and dextrose (70%) appeared to have particular potential because of the small sizes of the microbubbles (6 +/- 2 and 8 +/- 3 mu, respectively) and their prolonged in vitro persistence. The use of sonication to produce standardized, small and stable microbubbles should facilitate physiologic passage of the contrast agent through the capillary beds and allow two-dimensional imaging of the left heart myocardium during right-sided, aortic root, coronary sinus or intracoronary contrast injections.

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results.

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion: contrast echocardiography perspectives.

Contrast echocardiography may become a useful means of quantifying transmural regional myocardial perfusion patterns, experimentally and clinically, in a variety of settings. Contrast echocardiography has already been used in the operating room to study perfusion during coronary artery bypass graft (CABG) surgery. Other recent studies have demonstrated the ability of contrast echocardiography to predict wall motion improvement following acute myocardial infarction and therapeutic intervention. This is significant in the light of the discrepancy that has recently been shown between epicardial coronary vessel diameter and coronary flow. Studies suggest that both tissue and blood flow and volume may be quantitatively evaluated using contrast echocardiography, and these parameters ultimately may be used to assess tissue viability or vascular reserve. Contrast echocardiography techniques have been shown to be safe and reliable, and provide a high degree of spatial and temporal resolution.

Contrast echocardiography: review and future directions.

Recent developments and advances in contrast echocardiography have been made to improve the diagnosis and evaluation of cardiac structures and function. By coupling new developments in acoustic instrumentation with new contrast agents, information that was previously difficult or impossible to gather by standard 2-dimensional echocardiography can now be obtained. Numerous studies have been published confirming the advantages of using contrast during echocardiographic studies, particularly with stress testing and myocardial perfusion. This review aims to summarize (1) the various contrast agents that are available or being developed; (2) factors that have been found to affect the strength of enhanced signals; (3) the new developments in instrumentation that improve the ability of scanners to differentiate echo contrast from cardiac tissue; and (4) the documented and possible future uses of contrast echocardiography.

Effect of intracoronary injections of sonicated microbubbles on left ventricular contractility.

Despite the recent interest in contrast-enhanced echocardiography as a means of defining myocardial perfusion, the effects of echo contrast agents on left ventricular (LV) contractility in humans remains poorly defined. This is particularly relevant because intracoronary injection of contrast agents used for angiographic visualization of coronary arteries produces significant alterations in LV hemodynamics. The relation of LV end-systolic wall stress (sigma es) to rate-corrected velocity of fiber shortening (Vcfc), a load-independent index of contractility, was studied in 7 patients undergoing elective coronary arteriography. Two-dimensional and targeted M-mode echocardiographic and central aortic pressure tracings were recorded during injections of standard volumes of angiographic (7 to 9 ml of nonsonicated Renografin-76) and echocardiographic (1.5 to 2.0 ml of sonicated Renografin-76) contrast agents into the left main coronary artery. The order in which agents were injected was randomly determined. Myocardial contractility was assessed under control conditions and 5 and 15 seconds after injection. Alterations in contractility relative to control were measured as the change in Vcfc after elimination of afterload (sigma es) as a confounding variable. An injection of Renografin-76 adequate for angiographic imaging of coronary artery anatomy resulted in a significant depression of LV contractility (p less than 0.001) in conjunction with a tendency toward increased afterload (p = 0.12); recovery occurred by 15 seconds after injection. The smaller amounts of sonicated Renografin-76 required to give adequate contrast enhancement of the myocardium did not alter LV contractile state or afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between immediate outcome after cardiac surgery, homogeneous cardioplegia delivery, and ejection fraction.

BACKGROUND: Optimal myocardial protection during cardiac surgery with ischemic arrest is predicated on among other variables, homogeneous cardioplegia distribution. Contrast echocardiography has been shown to provide information regarding the intramyocardial distribution of cardioplegia solution. To test the hypothesis that information regarding cardioplegia distribution derived from contrast echocardiography may be associated with immediate clinical outcome after cardiac surgery, data from 21 patients were examined retrospectively. METHODS: Contrast-enhanced cardioplegia distribution patterns of the left ventricle short axis view obtained with transesophageal echocardiography were examined off-line by four observers blinded to clinical outcome. Contrast effect was scored for eight equally divided myocardial segments (0 = no contrast, 1 = nonuniform contrast, 2 = uniform contrast, 3 = excessive contrast). The scores were then averaged between segments and between observers to generate an antegrade, a retrograde, and a combined global contrast score for each patient. RESULTS: Seventeen patients were separated from bypass without difficulty (group A) and 4 patients required sustained inotropic therapy or an intra-aortic balloon pump to facilitate separation from bypass (group B). As would be expected, group A patients had a higher average preoperative ejection fraction than did group B patients (60 percent +/- 14 vs 31 percent +/- 7, p < 0.01). In group A, however, for 4 of 17 patients (23 percent), low preoperative ejection fraction was not predictive of postoperative exogenous circulatory support requirements. Group A patients also had significantly higher antegrade (1.6 vs 1.2, p < 0.02), retrograde (1.7 vs 1.1, p < 0.02), and combined global contrast scores (1.7 vs 1.1, p < 0.01) than did group B patients. All patients with low preoperative ejection fraction and low intraoperative contrast scores required exogenous support to separate from cardiopulmonary bypass. CONCLUSION: Contrast echocardiography makes possible an evaluation of the intensity and distribution of contrast-enhanced cardioplegia delivery and we believe the efficacy of intraoperative myocardial protection. Although low preoperative ejection fraction is a known predictor of poor immediate postoperative outcome following cardiac surgery, not all patients with low preoperative ejection fractions require inotropic support postoperatively. Our results suggest that monitoring cardioplegia distribution with contrast echocardiography may offer insight for better patient stratification based on intraoperative myocardial protection in patients with low ejection fraction. We believe a more extensive evaluation of this relationship should be pursued in a prospective manner.

Assessment of retrograde cardioplegia distribution using contrast echocardiography.

Retrograde cardioplegia has gained popularity in coronary and noncoronary cardiac operations. We have used contrast echocardiography in the open-chest canine model to compare the distribution of cardioplegia delivered antegrade in the aortic root versus retrograde through the coronary sinus, and to determine the effect of coronary occlusion on that delivery. With no coronary occlusion, antegrade cardioplegia was distributed to the entire left ventricle and septum whereas retrograde cardioplegia was distributed to the left ventricular free wall but had inconsistent delivery to the septum. Acute occlusion of the left circumflex coronary artery resulted in 57.06% +/- 9.52% of the left ventricle not being perfused by antegrade cardioplegia and occlusion of both the left circumflex and anterior descending coronary arteries caused a 65.46% +/- 18.5% reduction in perfusion by antegrade cardioplegia. Acute coronary occlusion had no effect on retrograde cardioplegia distribution. We conclude that retrograde cardioplegia is less homogeneous than antegrade cardioplegia in the intact coronary circulation but that retrograde cardioplegia preserves cardioplegia distal to acutely occluded coronary arteries. Furthermore, contrast echocardiography is a useful method of assessing myocardial perfusion and may have useful clinical applications.

Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion.

Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion.

The influence of intravenous Albunex injections on pulmonary arterial pressure, gas exchange, and left ventricular peak intensity.

Contrast ultrasonography may be used to assess regional tissue perfusion. The purpose of this study was to evaluate the safety and efficacy of a new, commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections were administered from peripheral intravenous (IV), right atrial (RA), and pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10, 20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately before and after each injection, pulmonary artery pressure (PAP) and oxygen tension (PO2) were determined. In addition, left ventricular cavity opacification was assessed visually and by videodensitometric off-line analysis. Visual assessment was performed by four blinded observers who graded on a scale of 0 to 3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement; and 3 = attenuation of the ultrasound signal following a contrast injection). Peak pixel intensity was also determined with videodensitometric analysis. Results showed that significant changes in PAP or PO2 were not noted after Albunex injections, regardless of injection site or dose range. The average change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS). The left ventricular cavity peak pixel intensity was dependent on both injection site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced forward output states affect the left ventricular opacification of intravenously administered Albunex.

Albunex is an Food and Drug Administration-approved ultrasound contrast agent used for the enhancement of left ventricular endocardial borders. To determine the efficacy of intravenously administered Albunex with regard to left ventricular opacification (LVO), a retrospective analysis of 117 patients who received 202 injections of Albunex for enhancement of endocardial borders was done (dose 0.08 to 0.22 ml /kg). Patients were routinely referred to our echocardiography laboratory for stress echocardiography for standard indications. Optimized settings for contrast enhancement (3.5 MHz transducer frequency and maximum dynamic range) were used. Four observers graded LVO on a scale from 0 to 3 (0 = no Albunex seen in the ventricular cavity; 3 = Albunex densely seen in the ventricular cavity). Overall, LVO was reported in 166 (82%) of 202 injections or in 91 (78%) of 117 patients. A significant reduction in LVO was noted in patients with mitral regurgitation, tricuspid regurgitation, atrial fibrillation, systolic dysfunction, or pulmonary hypertension (increased pulmonary artery systemic pressure). LVO was seen in 88% of the patients without these conditions. However, only 12 (44%) of 27 patients with one or more of the above conditions had LVO (p < 0.05). LVO can be achieved in the majority of patients after intravenously administered Albunex when imaged with optimal transducer settings. A subset of patients with systolic dysfunction, mitral regurgitation, tricuspid regurgitation, atrial fibrillation, or increased pulmonary artery systemic pressure has less effective LVO with Albunex. Heart disease associated with decreased forward flow appears to be associated with diminished LVO.

Sonicated echocardiographic contrast agents: reproducibility studies.

This article describes the production, analysis, and reproducibility of forming microbubbles for contrast ultrasound imaging. The sonication method used to generate microbubbles was tested by four independent observers, and a subsequent laser particle counter analysis of microbubble size and concentration determined the reproducibility of the method. The results indicated that the mean bubble size was 3.3 +/- 1.2 microns for the entire group, based on three trials of each of the four participants. The characteristics of the bubble size of the microbubbles between observers were assessed with a Poisson distribution with the reproducibility based on the sample mean for each observer's trials. Standardization and calibration of the laser particle counter was accomplished with commercially available latex spheres, sonicated albumin microspheres, and a Coulter counter analysis. Our results indicate that the sonication technique generates small microbubbles with a reproducible uniform size distribution. The method of microbubble production is reproducible and can be widely applied for use in contrast echocardiographic perfusion imaging of tissue in a variety of research and clinical studies.

Contrast echocardiography displays increased subendocardial perfusion after nitroglycerin administration.

A mechanism proposed to contribute to the antianginal effect of nitroglycerin is a redistribution of coronary blood flow to the subendocardium. Contrast echocardiography combines ultrasound with echogenic contrast agents to assess regional myocardial perfusion. This study aims to assess the effect of nitroglycerin on myocardial transmural perfusion with contrast echocardiography in humans. Nine patients scheduled for coronary angiography received 300 microg intracoronary nitroglycerin. Contrast echocardiographic studies were performed before and immediately after the administration of intracoronary nitroglycerin. Videodensitometric analysis was performed off-line to measure subendocardial and subepicardial opacification. Subendocardial opacification greater than subepicardial opacification increased from six of 13 patients before nitroglycerin administration to 11 of 13 after nitroglycerin administration (p <0.05). Similarly, these observations increased from nine of 13 patients to 13 of 13 after nitroglycerin administration during diastole (p <0.05). Contrast echocardiography demonstrates increased subendocardial perfusion after the administration of nitroglycerin in these patients.

Optimizing albunex in the left ventricle: an analysis of the technical parameters of four ultrasound systems in canines and humans.

Albunex, an intravascular ultrasound contrast agent, has been used clinically to enhance echocardiographic images. The purpose of this study if (1) to determine whether varying the settings on commercially available ultrasound machines has an effect on left ventricular opacification after intravenously administered Albunex and if there is an effect on left ventricular opacification and (2) to determine the ideal settings for each ultrasound scanner. Six canine hearts were imaged with 1 ml injections of intravenously administered Albunex while varying the transducer frequency, preprocessing curves, postprocessing curves, and dynamic range on a variety of ultrasound units. Subsequently 50 human subjects underwent imaging with the various machines while the dynamic range and transducer frequencies were altered. All subjects received two or three intravenous injections of 10 ml Albunex. The opacification of the left ventricular cavitary images in both parts of the study were interpreted visually on a scale of 0 to 4 (0 = none, 1 = trace, 2 = moderate, 3 = dense, and 4 = ideal) by four observers. The maximum compression and transducer frequency of 3.5 MHz showed significant improvement of left ventricular opacification in both canines and humans. These studies have shown that (1) varying the ultrasound unit's parameters affects the quality of left ventricular imaging when Albunex is used to enhance the image, and (2) higher compression and a transducer frequency of 3.5 MHz tend to enhance Albunex images of canine and human hearts.

In vitro calculation of flow by use of contrast ultrasonography.

Contrast echocardiography has been used for qualitative assessment of cardiac function, and its potential for quantitative assessment of blood flow is being explored. With the development of an ultrasound contrast agent capable of passage through the microcirculation, a mathematical model based on classic dye dilution theory, and a digital ultrasound acquisition system, absolute quantitation of myocardial perfusion may be feasible. This study validates the mathematical model in a simple in vitro tube system. Flow was delivered at variable rates through an in vitro tube system while a longitudinal section was imaged with a modified commercial ultrasound scanner. Albunex contrast agent was injected, and videointensity data were captured and analyzed off line. Time-intensity curves were generated, and flow was calculated by use of a mathematical model derived from classic dye dilution mathematics. For 39 different flow rates, ranging for 9.2 to 110 ml/seconds, a correlation coefficient of r = 0.928 (p < 0.001) with a slope of 0.97 was calculated. We conclude that (1) contrast ultrasonography is capable of quantitative determination of flow in an in vitro system, and (2) a mathematical model based on dye dilution theory can be used to calculate flow with accuracy and precision.

Contrast echocardiography: current and future applications.

Recent updates in the field of echocardiography have resulted in improvements in image quality, especially in those patients whose ultrasonographic (ultrasound) evaluation was previously suboptimal. Intravenous contrast agents are now available in the United States and Europe for the indication of left ventricular opacification and enhanced endocardial border delineation. The use of contrast enables acquisition of ultrasound images of improved quality. The technique is especially useful in obese patients and those with lung disease. Patients in these categories comprise approximately 10% to 20% of routine echocardiographic examinations. Stress echocardiography examinations can be even more challenging, as the image acquisition time factor is critically important for accurate detection of coronary disease. Improvements in image quality with intravenous contrast agents can facilitate image acquisition and enhance delineation of regional wall motion abnormalities at the peak level of exercise. Recent phase III clinical trial data on the use of Optison and several other agents (currently under evaluation) have revealed that for approximately half of patients, image quality substantively improves, which enables the examination to be salvaged and/or increases diagnostic accuracy. For the "difficult-to-image" patient, this added information results in (1) enhanced laboratory efficiency, (2) a reduction in downstream testing, and (3) possible improvements in patient outcome. In addition, substantial research efforts are underway to use ultrasound contrast agents for assessment of myocardial perfusion. The detection of myocardial perfusion during echocardiographic examinations will permit the simultaneous assessment of global and regional myocardial structure, function, and perfusion-all of the indicators necessary to enable the optimal noninvasive assessment of coronary artery disease. Despite the added benefit in improved efficacy of testing, few data exist regarding the long-term effectiveness of these agents. Currently under evaluation are the clinical and economic outcome implications of intravenous contrast agent use for daily clinical decision making in a variety of patient subsets. Until these data are known, this document offers a preliminary synthesis of available evidence on the value of intravenous contrast agents for use in rest and stress echocardiography. At present, it is the position of this guideline committee that intravenous contrast agents demonstrate substantial value in the difficult-to-image patient with comorbid conditions limiting an ultrasound evaluation of the heart. For such patients, the use of intravenous contrast agents should be encouraged as a means to provide added diagnostic information and to streamline early detection and treatment of underlying cardiac pathophysiology. As with all new technology, this document will require updates and revisions as additional data become available.