Role of intravenous ultrasound contrast in stress echocardiography

Intravenous newer generation perfluorocarbon containing microbubbles have been shown to enhance endocardial borders, especially during harmonic imaging. Although this significantly improves the detection of wall-motion abnormalities during stress echocardiography, intermittent imaging consistently results in myocardial contrast following intravenous infusions or injections of perfluorocarbon microbubbles. Detection of myocardial perfusion abnormalities during both exercise and pharmacologic stress echocardiography appears to be feasible clinically with either intravenous injections or continuous infusions of microbubbles using intermittent harmonic imaging. Accelerated intermittent harmonic imaging allows one to rapidly acquire both myocardial perfusion and wall motion during exercise and dobutamine stress echocardiography.     

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.     

Comparison of myocardial contrast echocardiography with NC100100 and (99m)Tc sestamibi SPECT for detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction

OBJECTIVE—To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction.
PATIENTS AND INTERVENTIONS—22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting ^99mTc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect.
RESULTS—Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE.
CONCLUSIONS—The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account.


Keywords: myocardial contrast echocardiography; NC100100; single photon emission computed tomography; perfusion     

Dipyridamole stress echocardiography and ultrasonic myocardial tissue characterization in predicting myocardial ischemia, in comparison with dipyridamole stress Tc-99m MIBI SPECT myocardial imaging

The purpose of this study was to validate whether dipyridamole stress ultrasonic tissue characterization with cyclic variation of integrated backscatter (CVIBS) compared with dipyridamole stress echocardiography and dipyridamole stress Tc99m-MIBI SPECT myocardial perfusion scintigraphy could predict myocardial ischemia in patients with chronic coronary artery disease. Twenty patients (16 M, 4 F) who had coronary angiography for stable angina pectoris were included in the study. Mean age was 62 +/- 8 years. The left ventricle was divided into 16 segments. Regional wall motion analysis and CVIBS measurements were obtained from 16 myocardial segments at rest and after dipyridamole (0.84 mg/kg) infusion. After 10 minutes, Tc-99m MIBI (10 mCi) was injected and SPECT myocardial imaging was performed. After 3 hours, 25 mCi Tc-99m MIBI was reinjected and rest images were obtained. A total of 320 ventricular wall segments were evaluated. Two hundred and six ventricular wall segments were supplied by stenotic coronary arteries and 114 segments were supplied by normal coronary arteries. Dipyridamole stress Tc-99m MIBI SPECT studies showed abnormal myocardial perfusion in 176 segments and normal perfusion in 144 segments. Transient regional wall motion abnormality was detected in 116 segments. A significant decrease in CVIBS after dipyridamole stress was detected in 184 segments. The sensitivity and specificity of dipyridamole stress echocardiography, Tc-99m MIBI SPECT, and CVIBS were 56% and 100%, 85% and 92%, and 89% and 100%, respectively, compared with the results from coronary angiography. Dipyridamole stress ultrasonic tissue characterization with CVIBS may provide more sensitive detection of myocardial ischemia than dipyridamole stress echocardiography and may be as valuable as dipyridamole stress myocardial perfusion scintigraphy.     

Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT

OBJECTIVE—To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients.
DESIGN—Cohort study.
SETTING—Regional cardiothoracic unit.
PATIENTS—49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress.
MAIN OUTCOME MEASURES—Regional myocardial perfusion by SPECT, performed with ^99mTc tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity.
RESULTS—Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wall, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images.
CONCLUSIONS—Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.


Keywords: myocardial contrast echo; SPECT; coronary artery disease; dipyridamole stress     

Contrast echocardiography for myocardial perfusion imaging using intravenous agents: progress and promises.

AIMS: This article is a convenient overview to assist the interested echocardiographist towards acquiring his own experience in the field of myocardial perfusion imaging using intravenous contrast agents. This goal is now pursued in many centres, since contrast echo holds the advantages of cardiac ultrasound (non-invasiveness, high spatial and temporal resolution, wide availability, use of non-ionizing radiation), and because a variety of transpulmonary agents-together with a spectrum of imaging modalities-are becoming available. METHODS AND RESULTS: Many technical considerations need to be addressed for optimal myocardial perfusion imaging: characteristics of the contrast medium (air-filled or perfluorocarbon filled and/or encapsulated agents), modality of administration (bolus injection or continuous infusion) and interaction between microbubbles and ultrasound (dependency on power output). Moreover, intermittent harmonic imaging, intermittent harmonic power Doppler, pulse inversion and amplitude modulation imaging have all been developed to enhance microbubble detection over myocardial tissue. These new acquisition modalities also yield specific artifacts impacting on myocardial perfusion assessment. Finally, acute myocardial infarction and chronic ischaemic heart disease (at baseline and during stress) are the most studied clinical models for perfusion imaging with contrast echo, and are reviewed in this article. CONCLUSION: Perfusion imaging with intravenous contrast agents has never been as close to widespread clinical use as it is today, but many methodological issues remain unsettled before the wish of the contrast echocardiographist comes true: that is, a cheap, user-friendly and widely available technology that would disclose new information in echocardiography.     

Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography.

OBJECTIVES: We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND: Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time. METHODS: One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM w ere assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS: In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%,respectively) with the highest accuracy (86%). CONCLUSIONS: The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.     

The value of myocardial contrast echocardiography compared with SPECT in detecting myocardial perfusion abnormalities in patients with anterior acute myocardial infarction

BACKGROUND: Microvasculature damage after myocardial infarction (MI), known as "no-reflow" phenomenon, may occur in some patients with acute MI in spite of invasive treatment and opened infarct-related coronary artery. There are several non-invasive and invasive methods used for the coronary flow assessment at the tissue level. AIM: To compare the value of intravenous contrast echocardiography (MCE) in detecting myocardial perfusion defects in patients with acute MI with (99m)Tc MIBI SPECT study. METHODS: Sixteen patients (11 males, 5 females, mean age 55.4+/-10.2 years) underwent primary coronary angioplasty or facilitated angioplasty (with reduced dose of a fibrinolytic drug and glycoprotein IIb/IIIa inhibitor) (PCI) for acute anterior MI. TIMI grade flow, TIMI Myocardial Perfusion Grade (TMPG), corrected TIMI frame count (cTFC), wall motion score index (WMSI) and segmental perfusion by myocardial contrast echocardiography (MCE) were estimated in real time before and immediately after PCI. MCE was repeated on the third day after PCI. All patients underwent (99m)Tc MIBI SPECT study (SPECT) while at rest on the third day after PCI. The area at risk was defined as the number of segments with no perfusion before angioplasty. Reflow was defined as an increase in contrast score in the same segments after angioplasty. RESULTS: Baseline MCE showed 95 segments with perfusion defects. Immediately after PCI, 77 segments were found with perfusion defect; in 10 patients improvement of myocardial perfusion was observed whereas in 6 patients perfusion defect remained unchanged. On the third day further improvement was observed in 8 patients. The number of segments with perfusion defect decreased to 53. SPECT detected perfusion defect in 54 segments. The agreement between MCE and SPECT for detecting perfusion abnormality was 98% (kappa 0.94). CONCLUSIONS: MCE is a safe technique for detecting myocardial perfusion in patients with acute MI. MCE proves that both primary and facilitated angioplasty improve myocardial perfusion in two thirds of patients with acute MI. Serial MCE allows identification of patients with both early and late improvement of myocardial perfusion. There is a very strong correlation between MCE and SPECT in the assessment of perfusion defects.     

Assessment of myocardial perfusion with intravenous contrast echocardiography: comparison with (99) Tc-tetrofosmin single photon emission computed tomography and dobutamine echocardiography

The aim of the study was to evaluate the accuracy of intermittent, harmonic power Doppler (HPD) during intravenous Levovist infusion in identifying myocardial perfusion abnormalities in patients with recent infarction. Fifty-five patients with first acute myocardial infarction, successfully treated by primary PTCA, were studied after 1 month by myocardial contrast echocardiography (MCE), 99mTc tetrofosmin single photon emission computed tomography (SPECT), and low dose dobutamine echocardiography (DE). Scoring myocardial perfusion as normal, moderately, or severely reduced; MCE and SPECT were in agreement in 71% of segments(k = 0.414). Discordance was mainly due to ventricular walls with normal enhancement by MCE and moderate perfusion abnormalities by SPECT. Scoring perfusion as present or absent, the agreement significantly improved up to 86% (k = 0.59). Sensitivity and specificity of HPD for identifying SPECT perfusion defects were 63% and 93%, respectively. The agreement between MCE and SPECT was higher(85%, k = 0.627)in patients with anterior infarction. An improvement in regional contractile function was noted after dobutamine in 79 dysfunctional segments. A normal perfusion or a moderate perfusion defect by MCE were detected in 71 of 79 of these segments, while a severe perfusion defect was observed in 59 of 85 ventricular segments without dobutamine-induced wall-motion improvement. Sensitivity and specificity by HPD in detecting segments with contractile reserve were 90% and 69%, respectively. Thus, intermittent HPD during Levovist infusion allows myocardial perfusion abnormalities to be detected in patients with recent infarction. This method has a limited sensitivity but a high specificity in detecting SPECT perfusion defects, and a good sensitivity but a limited specificity in detecting contractile reserve.     

Comparison of usefulness of dipyridamole stress myocardial contrast echocardiography to technetium-99m sestamibi single-photon emission computed tomography for detection of coronary artery disease (PB127 Multicenter Phase 2 Trial results)

We hypothesized that assessment of hyperemic myocardial blood flow (MBF) velocity using myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD). We also postulated that only a single MCE study during stress is required for the detection of CAD in patients with normal function at rest. Patients with known or suspected CAD referred for dipyridamole stress technetium-99m sestamibi single-photon emission computed tomographic (SPECT) studies were enrolled. MCE was performed concurrently with SPECT using continuous infusions of PB127 during intermittent harmonic power Doppler imaging at multiple pulsing intervals. MCE and SPECT were compared in 43 of 54 patients who had adequate studies using both techniques. In 15 of the 43 patients, coronary angiography was performed within 30 days of the MCE/SPECT tests. Overall concordance for classification of patients as normal versus abnormal was 84% (kappa = 0.63) between the 2 tests. When false-negative SPECT scans were corrected for results of angiography, concordance increased to 93% (kappa = 0.82). For territorial analysis, concordance between MCE and SPECT for location of perfusion defects was 65% (kappa = 0.41) and 74% (kappa = 0.61) after SPECT was corrected by angiography. In patients with normal function at rest, a single stress MCE perfusion study allowed identification of CAD with the same concordance as rest/stress perfusion studies. In conclusion, visual assessment of regional differences in MBF velocity using PB127 allows detection of CAD with good concordance compared with technetium-99m sestamibi SPECT. In patients with normal left ventricular function at rest, a single stress PB127 MCE perfusion study is adequate for the detection of CAD.     

Detection of angiographically significant coronary artery disease with accelerated intermittent imaging after intravenous administration of ultrasound contrast material

BACKGROUND: Accelerated intermittent harmonic imaging (AII) is used to detect myocardial perfusion abnormalities after intravenous injection of ultrasound contrast medium. A low mechanical index and frame rates of 10 to 20 Hz are used to allow simultaneous wall motion analysis. The purpose of this study was to determine whether the myocardial contrast enhancement achieved with AII can be used to detect angiographically significant coronary artery disease during stress echocardiography. METHODS: We gave intravenous perfluorocarbon containing microbubbles to 45 patients (total of 270 regions) during dobutamine (n = 27) or exercise (n = 18) stress testing with AII. Quantitative angiography was performed on all patients after the stress echocardiograms were interpreted. RESULTS: Quantitative angiography showed >50% diameter stenosis of at least 1 vessel in 32 patients (total of 118 regions). There were visually evident contrast defects in 100 (85%) of these regions, and wall motion was abnormal in 64 (54%). Overall, there was agreement between regional perfusion and quantitative angiographic findings in 217 of the 270 regions (kappa = 0.61; 80% agreement). Agreement with findings at quantitative angiography was good for both dobutamine stress (kappa = 0.66; 83% agreement) and exercise (kappa = 0.53; 77% agreement). The greatest incremental benefit of AII versus wall motion was gained during dobutamine stress. The contrast studies depicted 90% of the regions supplied by a vessel with >50% stenosis, whereas wall motion depicted only 32% (P =.001). CONCLUSIONS: The results of this study indicated that accelerated intermittent perfusion imaging during stress echocardiography can improve the sensitivity of the study in detecting angiographically significant coronary artery disease, especially during dobutamine stress.     

Detection of coronary artery disease using real-time myocardial contrast echocardiography: a comparison with dual-isotope resting thallium-201/stress technectium-99m sestamibi single-photon emission computed tomography

Real-time myocardial contrast echocardiography (MCE) has the potential to evaluate myocardial perfusion and wall motion (WM) simultaneously. The purposes of this study were to correlate the diagnostic value of MCE with radionuclide single-photon emission computed tomography (SPECT), and to assess the sensitivity and specificity of real-time MCE in detecting coronary artery disease (CAD). Seventy patients with clinically suspected CAD underwent MCE and SPECT at baseline and after dipyridamole infusion. Segmental perfusion with MCE using low mechanical index after 0.3–0.4-ml bolus injections of perfluorocarbon exposed sonicated dextrose albumin solution was performed. All patients had a dual-isotope (rest thallium-201, stress sestamibi) study performed both at baseline and after dipyridamole infusion, and 40 patients had subsequent quantitative coronary angiography. Abnormalities were noted in 27 patients (38.6%) by MCE, in 29 patients (41.4%) by WM analysis, and in 30 patients (42.9%) by SPECT imaging. When MCE and WM analysis were combined, the agreement with SPECT imaging improved from 75.7% (Kappa = 0.50) to 82.0% (Kappa = 0.62). In 40 patients (120 territories) who underwent coronary angiography, good perfusion concordance was achieved for the left anterior descending and left circumflex arteries, and was fair for the right coronary arteries. Compared with quantitative angiography, there was no difference in sensitivity, specificity, and accuracy in detecting significant CAD among the three modalities. The combination of MCE and WM had a better sensitivity (84%), specificity (93.3%), and accuracy (87.5%) than the MCE and WM analysis alone. However, the difference did not reach statistical significance. Real-time MCE has a good agreement with SPECT imaging for detecting CAD. The combination of MCE and WM appears to have higher sensitivity, specificity, and accuracy in detecting CAD than either technique alone.     

Non-invasive detection of coronary artery stenosis: a comparison among power-Doppler contrast echo, 99Tc-Sestamibi SPECT and echo wall-motion analysis

BACKGROUND: Power-Doppler imaging is a recently developed method for myocardial contrast echocardiography (MCE). It can selectively evaluate the signal coming from an ultrasound contrast agent, allowing myocardial perfusion studies. OBJECTIVE: To compare the ability of power-Doppler MCE with stress-echo wall-motion and nuclear scan imaging (SPECT) to assess myocardial ischaemia during pharmacological stress, using coronary angiography as reference. METHODS: In 25 patients the three non-invasive imaging modalities were acquired during a single dipyridamole stress test (so as to avoid stress variations). Power-Doppler MCE was acquired using continuous intravenous infusion of Levovist. Echo wall-motion was acquired too. At peak stress 99Tc-Sestamibi was injected; stress SPECT images were acquired 30 min after injection. RESULTS: Power-Doppler MCE and SPECT showed 84% concordance (21 of 25 patients; kappa=0.67) for detection of ischaemia. Concordance based on coronary artery territories for normal perfusion versus fixed defects versus reversible defects was 92% (69 of 75; kappa=0.81), with 100% for left anterior descending, 92% for right coronary artery and 84% for circumflex. Power-Doppler MCE had lower sensitivity than SPECT (89 versus 100%) but higher specificity (100 versus 88%) for identification of stenotic (> or = 70%) coronary arteries as assessed by angiography. Echo wall-motion analysis showed the lowest sensitivity (68%) with 100% specificity. Accuracy was 94% for both power-Doppler MCE and SPECT, and 83% for wall-motion analysis. CONCLUSION: Power-Doppler MCE is a sensitive and specific method for identification of myocardial perfusion during pharmacological stress. Accuracy of power-Doppler MCE for stenotic coronary arteries appears to be slightly higher than stress-echo wall-motion and similar to SPECT.     

Quantitative intravenous myocardial contrast echocardiography predicts recovery of left ventricular function after revascularization in chronic coronary artery disease

BACKGROUND: Quantitative intravenous myocardial contrast echocardiography (MCE) has been shown to measure regional myocardial blood flow velocity noninvasively. PURPOSE: To determine whether quantitative intravenous MCE could be used clinically to predict functional recovery after revascularization in patients with chronic coronary artery disease. METHODS: Twenty-eight patients with chronic stable coronary artery disease and resting regional left ventricular dysfunction were included in this study. The study permits myocardial perfusion analysis by intravenous MCE before revascularization with continuous infusion of Levovist and intermittent ultrasonic exposure. Wall motion assessment by echocardiography at rest was repeated after long-term follow-up period (7 +/- 2 months). In dysfunctional segments, we analyzed myocardial perfusion quantitatively by fitting to an exponential function, Y = A(1 - e-betat) to obtain the rate of rise (beta) of background-subtracted intensity, which represented myocardial blood flow velocity. RESULTS: Of the 101 revascularized dysfunctional segments, MCE was adequately visualized in 91 (90%) segments, and wall motion was recovered in 45 (49%) segments. The value of beta in the recovery segments was significantly higher than that in nonrecovery segments (0.80 +/- 0.50 vs 0.39 +/- 0.24, P < 0.001). The value of beta > 0.5 predicted recovery of segmental function with a sensitivity of 71%, specificity of 78%. CONCLUSION: Quantitative intravenous MCE can predict functional recovery after revascularization in patients with chronic coronary artery disease.     

Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice: Comparison with wall motion and Technetium-99m sestamibi single-photon emission computed tomography

Objectives. We sought to assess the feasibility and accuracy of myocardial contrast echocardiography (MCE) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction (MI).Background. Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI. However, its reliability in routine practice is unclear.Methods. Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent (NC100100). All patients underwent single-photon emission computed tomography (SPECT) after the injection of technetium-99m (Tc-99m) sestamibi at rest. Quantitative and semiquantitative SPECT, wall motion and digitized echocardiographic data were interpreted independently. The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects, as well as for detection of patients with extensive perfusion defects (>12% of left ventricle).Results. In segments with diagnostic MCE, the segmental sensitivity ranged from 14% to 65%, and the specificity varied from 78% to 95%, depending on the dose of contrast agent. Using both segment- and patient-based analysis, the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode. For the detection of extensive defects, the sensitivity varied from 13% to 48%, with specificity from 63% to 100%. Harmonic imaging remained the most accurate approach. Time since MI and SPECT defect location and intensity were all determinants of the MCE response. The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities. The combination of wall motion and MCE assessment gave the best balance of sensitivity (46% to 55%) and specificity (82% to 83%).Conclusions. Although MCE is specific, it has limited sensitivity for detection of moderate or severe perfusion defects, and it underestimates the extent of SPECT defects. The best results are obtained by integration with wall motion. More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice.     

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.     

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.     

Real-time myocardial contrast echocardiography for the detection of stress-induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon emission computed tomography

BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising technique for assessing myocardial perfusion. The purpose of this study was to test whether realtime MCE can be used to detect functionally significant coronary artery stenosis in patients with known or suspected coronary artery disease. Myocardial contrast echocardiographic studies were compared with nearly simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT) as a clinical standard reference to evaluate regional myocardial perfusion defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10 ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56 mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber views, each divided into 6 segments. Tracer uptake and myocardial opacification were visually analyzed for each segment by two pairs of blinded observers and graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial segments, myocardial opacification by MCE was uninterpretable in 143 (18%) segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments. Interobserver variability for MCE was good with concordance rates of 83% (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental level. In the diagnosis of fixed and reversible defects, and of normal perfusion, concordance rates were 73, 65 and 83%, respectively. When analysis was performed at the regional level, we found comparable levels of concordance rates for LAD (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion territories. CONCLUSIONS: These findings suggest that realtime MCE is a clinically acceptable method to evaluate myocardial perfusion defects during dipyridamole stress testing.     

Usefulness of power Doppler contrast echocardiography to identify reperfusion after acute myocardial infarction

Microvascular integrity, as seen by myocardial contrast echocardiography (MCE), assesses whether myocardium has been successfully reperfused after an acute myocardial infarction. Until now this has been demonstrated only with intracoronary injection of an ultrasound contrast agent. Power Doppler imaging is a recently developed myocardial contrast echocardiographic method that counts the contrast microbubbles destroyed by ultrasounds and displays this number in color. This study sought to evaluate whether power Doppler MCE is able to visualize myocardial reperfusion during intravenous contrast injection. Thirty patients were evaluated 2 days after their first myocardial infarction during intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA). Coronary artery angiography and single-photon emission computed tomography (SPECT) were used as reference techniques. A 16-segment left ventricular model was used to relate perfusion to coronary artery territories. Sensitivity and specificity of power Doppler MCE for segments supplied by infarct-related arteries were 82% and 95%, respectively. Accuracy of power Doppler MCE and SPECT were similar (90% vs 92% on segmental basis and 98% vs 98% on coronary artery territory basis). Two-dimensional echocardiography was repeated after 6 weeks. Segments recovering wall motion after 6 weeks were defined as stunning myocardium. Dysfunctional but perfused myocardium at day 2 after the infarction showed a better late recovery of wall motion compared with dysfunctional but nonperfused myocardium (p <0.001). In conclusion, harmonic power Doppler imaging is a sensitive and specific method for the identification of myocardial reperfusion early after myocardial infarction. It yields prognostic information for late recovery of ventricular function differentiating stunning (dysfunctional but perfused) from necrotic myocardium (dysfunctional and nonperfused).     

Dipyridamole myocardial perfusion single photon emission computed tomography in patients with slow coronary flow

OBJECTIVE: Several studies have indicated that the velocity of contrast dye increases after intravenous dipyridamole infusion in patients with a slow-flow pattern (SFP). In this study we compared the results of coronary arteriography and exercise myocardial perfusion single photon emission computed tomography (SPECT) in patients with SFP. We also investigated the changes in myocardial perfusion in patients with abnormal exercise myocardial perfusion SPECT by using a pharmacological stress test with dipyridamole. DESIGN AND PATIENTS: This study included 60 patients who revealed SFP in their coronary arteriograms. Slow coronary flow diagnoses were made using the frame count method. A single day rest-exercise technetium-99m hexakis-2-methoxy-isobutyl isonitrile (Tc-99m MIBI; Du Pont Pharma SA, Belgium) SPECT was performed in all patients. Patients who had reversible perfusion defect (RPD) on the exercise SPECT were evaluated with dipyridamole myocardial perfusion scintigraphy.RESULTS Patients with SFP revealed both higher frame counts in native coronary arteries and higher mean frame counts. The coronary frame count was 26.4 +/- 3.5 in control patients and 64.40 +/- 16.64 in patients with SFP, respectively (P < 0.001). Exercise perfusion SPECT showed RPD in 17 patients (group 1), but was normal in 43 others (group 2). There were no statistically significant differences between groups 1 and 2 in frame counts. Myocardial perfusion was normalized in all 17 patients of group 1 after dipyridamole infusion. CONCLUSIONS: In patients with SFP perfusion, changes may improve with dipyridamole infusion. This study indicates that this improvement can be shown by dipyridamole SPECT. Furthermore, no correlation was observed between the time needed to fill a native coronary artery and RPD of the myocardium.