Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study

OBJECTIVES: The aim of this study was to verify the accuracy of using myocardial contrast echocardiography (MCE), to quantify regional myocardial blood flow (MBF), and to evaluate myocardial viability in comparison to that measured by radiolabeled microsphere and pathologic examination. METHODS: Epicardial MCE was obtained in five myocardial ischemic dogs with constant microbubble intravenous infusion. After the video intensity (VI, y) versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y = A(1 - e(-beta t)), the MBF was calculated as the product of A (microvascular cross-sectional area or myocardial blood volume) and beta (mean myocardial microbubble velocity). The MBF was also obtained by radiolabeled microsphere method. RESULTS: The MBF derived by radiolabeled microsphere method in the normal, ischemic, and infarcted region was 1.5 +/- 0.3, 0.7 +/- 0.3, and 0.3 +/- 0.2 ml/min per gram, respectively; P < 0.01. The product of A and beta in those regions was 52.5 +/- 15.1, 24.4 +/- 3.9, and 3.7 +/- 3.8, respectively; P < 0.01. The normalized product of A and beta correlated well with normalized MBF (r = 0.81, P = 0.001). CONCLUSION: Our initial study demonstrated that MCE has an ability to assess MBF in ischemic myocardium in the experimental model. It may provide a potential capability to detect viable myocardium noninvasively after total persistent coronary occlusion in the clinical setting.     

Dynamic changes in microcirculatory blood flow during dobutamine stress assessed by quantitative myocardial contrast echocardiography

Background: Although dobutamine‐atropine stress echocardiography (DASE) has been widely used for evaluating patients with coronary artery disease (CAD), dynamic changes that occur at microcirculatory level during each stage of stress have not been demonstrated in humans. Aim: We sought to determine variations in myocardial blood flow (MBF) during DASE using quantitative real time myocardial contrast echocardiography (RTMCE). Methods: We studied 45 patients who underwent coronary angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium (β) and MBF reserves were obtained at baseline, intermediate stage (70% of maximal predicted heart rate), peak stress, and recovery phase. Results: β and MBF reserves were lower in patients with than without CAD at intermediate (1.65 vs. 2.10; P = 0.001 and 2.44 vs. 3.23; P = 0.004) and peak (1.63 vs. 3.00; P < 0.001 and 2.14 vs. 3.98; P < 0.001, respectively). In patients without CAD, β, and MBF reserves increased from intermediate to peak and decreased at recovery, while in those without CAD reserves did not change significantly. Optimal cutoff values of β reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with areas under the curves of 0.80 (95%CI = 0.67–0.94), 0.89 (95%CI = 0.79–0.99), and 0.69 (95%CI = 0.53–0.85). Sensitivity, specificity and accuracy for detecting CAD at intermediate stage were 68% (95%CI = 48–89), 85% (95%CI = 71–98), and 78% (95%CI = 66–90), at peak stress were 79% (95%CI = 61–97), 96% (95%CI = 89–100), and 89% (95%CI = 80–98), and at recovery were 74% (95%CI = 54–93), 65% (95%CI = 47–84), and 69% (95%CI = 55–82), respectively. Conclusion: RTMCE allows for quantification of dynamic changes in microcirculatory blood flow at each stage of DASE. The best parameter for detecting CAD in all stages was β reserve. (Echocardiography 2011;28:993‐1001)     

应用实时心肌超声造影定量评价心功能对急性心肌梗死犬心肌血流量的影响

目的:探讨心功能对心肌梗死犬心肌血流灌注的影响。方法:18只健康杂种犬于前降支分出的第1对角支远端约1cm处结扎3h,应用心肌超声造影(MCE)定量分析左室前壁中间段和下壁中间段心肌血流量(MBF)。结果:17只犬成功建立急性心肌梗死模型。根据结扎3h后左室整体射血分数(EF)分为2组:A组(EF≥50%)7只,B组(EF<50%)10只。B组左室前壁中间段和下壁中间段MBF均低于A组,但2组之间差异无统计学意义;与结扎前相比,2组左室前壁中间段MBF均明显降低,差异有统计学意义(P<0.05),A组左室下壁中间段MBF略升高,B组则降低,但均差异无统计学意义。结论:心功能对MBF有一定的影响,可能会低估冠状动脉血流储备和高估狭窄程度,在以MCE诊断冠心病时应注意心功能对MBF的影响。     

Assessment of myocardial viability using myocardial contrast echocardiography

Myocardial contrast echocardiography (MCE) is a technique that uses microbubbles as a tracer during simultaneous ultrasound of the heart. The microbubbles can be used to provide quantitative information regarding the adequacy of myocardial blood flow (MBF), as well as the spatial extent of microvascular integrity. In acute myocardial infarction, MCE can identify the presence of collateral flow within the risk area, and can therefore predict preservation of myocardial viability and ultimate infarct size even prior to reperfusion. After reperfusion, the extent of microvascular no-reflow can be determined, and has significant implications for recovery of left ventricular function. In chronic ischemic heart disease, MCE has also been shown to successfully differentiate viable from necrotic myocardium. This technique can accurately predict recovery of function after revascularization. More importantly, MCE can be used to identify viable segments that may help to prevent infarct expansion and remodeling, and thus improve patient outcomes.     

Intraoperative assessment of myocardial perfusion using contrast echocardiography

Myocardial contrast echocardiography is a new technique capable of assessing regional myocardial perfusion in vivo in real time. This article reviews the background, principles, experimental validation, and clinical uses of intraoperative myocardial contrast echocardiography. Data can be derived both for online visual and computer analyses. The technique can be useful in determining the sequence of bypass graft placement and the success of graft anastamoses. Anastamoses can be revised immediately if needed. It is hoped that this technique will improve intraoperative myocardial preservation and will diminish the rate of perioperative myocardial infarction.     

Assessment of myocardial viability with myocardial contrast echocardiography

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.     

Assessment of the vascularity of a left atrial mass using myocardial perfusion contrast echocardiography

Emerging applications of myocardial contrast echocardiography (MCE) include the evaluation of myocardial perfusion, the improvement of the definition of intracavitary structures, and evaluation of the relative perfusion of a cardiac mass. We present a case of a patient that was found incidentally to have a cardiac mass on transthoracic echocardiography. MCE was used to evaluate the vascularity of the mass. This case is compared with another patient with a left atrial thrombus, which represents an "avascular" cardiac mass by MCE.     

心肌声学造影定量心肌血流判断存活心肌的实验研究

目的　评价经静脉心肌声学造影 (MCE)判断存活心肌的可行性。方法　建立急性心肌梗死犬模型 ,经外周静脉持续滴注微泡造影剂 ,通过计算A·β值测定心肌相对血流量。以放射性微球法测定的心肌血流量 (MBF)为标准 ,了解A·β值测定MBF的准确性。通过A·β值估测心肌存活与否 ,病理检查验证其可靠性。结果　放射性微球法所测的正常区、缺血区、坏死区的MBF分别为 ( 1 5± 0 3)、( 0 7± 0 3)、( 0 3± 0 2 )ml·min-1·g-1;MCE测得的A·β值分别为 5 2 46± 15 0 9、2 4 36±3 89、3 74± 3 80 ;正常区、缺血区、坏死区的MBF和A·β值“标化”后分别为 1 0± 0 0、0 44± 0 17、0 17± 0 11和 1 0± 0 0、0 48± 0 0 9、0 0 7± 0 0 8,二者的相关性良好 (r=0 81,P =0 0 0 1)。MCE对坏死心肌的判定结果与病理结果吻合。结论　心肌声学造影可用于活体状态下评价存活心肌 ,“标化”后的A·β值 <0 2 3提示心肌坏死。     

Abnormal myocardial flow reserve in sickle cell disease: a myocardial contrast echocardiography study

Background: Sickle cell disease (SCD) is characterized by obstruction of microvessels leading to ischemia and necrosis. We have aimed to demonstrate whether myocardial contrast echocardiography (MCE) is able to detect myocardial perfusion abnormalities in SCD patients and to assess their relationship with left ventricle ( LV) perfusion and systolic function. Methods: A group of 25 patients with SCD and a control group of 19 normal individuals were studied. Using MCE, myocardial perfusion reserve indices (A, β, and A×β) were obtained, before and after hyperemia with dypiridamole. LV function was also analyzed: ejection fraction (EF), index of myocardial performance (IMP), the ratio of transmitral early-diastolic flow velocity E and the pulsed tissue Doppler mitral annular early diastolic velocity Ea (E/Ea) (E/Ea), tissue Doppler mitral annular peak systolic velocity (Sa), and peak systolic strain (S) were obtained. Results: Myocardial velocity (β) and myocardial blood flow (A×β) reserves were lower in the patients than in controls (1.7 ± 0.4 vs. 3.3 ± 0.2, P = 0.000 and 2.1 ± 0.6 vs. 4.1 ± 0.2, P = 0.000, respectively). In SCD patients, a correlation was found between β reserve and EF, IMP, Sa, E/Ea, and S% and between A×β reserve and Sa. Conclusions: MCE detected abnormal perfusion reserve in patients with SCD, which correlated with systolic function indices. This suggests that perfusion plays a role in SCD ventricular dysfunction.     

Assessment of myocardial perfusion by power contrast imaging using a new echo contrast agent

In a patient with previously documented myocardial infarction, we assessed myocardial perfusion by using power contrast imaging and a newer intravenous echo contrast agent. The images were captured and stored digitally, and various image processing algorithms were used to assess myocardial perfusion. An apical perfusion defect was clearly visualized, and it correlated with radionuclide findings.     

Triggered replenishment imaging reduces variability of quantitative myocardial contrast echocardiography and allows assessment of myocardial blood flow reserve

Assessment of replenishment kinetics (RK) following ultrasound-induced destruction of contrast microbubbles allows quantification of myocardial blood flow reserve (MBFR) applying the model f (t) = A (1 - e(-betat)), with parameter beta describing mean flow velocity and parameter A representing blood volume. However, few data on the variability and reproducibility of RK in a clinical setting are available. Therefore, we examined 30 patients in a rest-adenosine protocol in one center. Off-line quantification of real-time perfusion imaging (RTPI) and triggered replenishment imaging (TRI) was performed at two sites and compared with coronary angiography and flow reserve measurements. Parameter A was found to be robust in all investigated segments (coefficient of variation (CV) < 7.2%+/- 5.1). Variability was lowest for parameter beta using TRI in apical segments (CV 6.5%+/- 5.2, P < 0.01). Highest CV was found with RTPI in lateral segments (CV : 39.8%+/- 40.6). Concerning day-to-day reproducibility both methods revealed similar results within range of heterogeneity of myocardial blood flow. Both sites obtained significantly lower MBFR in patients with flow-limiting CAD, compared to subjects without (P < 0.01). Correlation of both sites showed close relationship (y = 0.88x + 0.45, r = 0.83, P < 0.0001), without systematic bias. TRI significantly reduces variability of RK in quantitative MCE. Assessment of MBFR allows investigator-independent evaluation of CAD.     

Quantification of images obtained during myocardial contrast echocardiography

This article describes currently used quantitative methods for analysis of data obtained during myocardial contrast echocardiography. The specific issues addressed are: obtaining time-intensity curves from the myocardium in order to derive transit rates of microbubbles through the myocardium; defining spatial distribution of flow within a myocardial segment; and color-coding algorithms used to define the extent and magnitude of hypoperfusion within a cross-section of the heart. These methods are being adopted by several companies dealing with acquisition and analysis of echocardiographic data and should become available soon for clinical use.     

Reproducibility of myocardial contrast echocardiography in human studies

Experimental and clinical studies were performed to assess the ability of myocardial contrast echocardiography for quantitation of regional myocardial blood flow. To evaluate whether myocardial contrast echocardiography is a reproducible technique in humans, 18 nonselected patients undergoing coronary angiography were studied. A total of 107 intracoronary injections into either the left or the right coronary artery were analyzed by computer assisted videodensitometry for peak intensity, contrast decay half-time, and area under the curve. By means of these parameters intraobserver, interobserver, and interinjection variability were determined. Intraobserver measurements showed lowest variability with correlation coefficients of 0.83 for contrast decay half-time, 0.93 for peak intensity, and 0.95 for area under the curve. Mean percent error varied between 6.8% (peak intensity) and 11.2% (area under the curve). The correlation coefficients for interobserver variability ranged from 0.73 for area under the curve to 0.97 for peak intensity. Mean percent error revealed a range between 7.5% for peak intensity and 19% for area under the curve. For interinjection variability, the correlation coefficient for contrast decay half-time was lower (0.56) than for peak intensity (0.73) and area under the curve (0.84). Mean percent error were higher than for intraobserver and interobserver variability (range 24.1% to 34.2%). Thus, intraobserver and interobserver variability for parameters derived from time-intensity curves after intracoronary injection of echo contrast agent in humans are sufficient and comparable to data from animal studies. Interinjection variability, however, showed a higher mean percent error.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of functional recovery using low-dose dobutamine and myocardial contrast echocardiography after acute myocardial infarction treated with successful thrombolytic therapy

OBJECTIVE: We studied the value of low-dose dobutamine stress echocardiography (LDDE) and myocardial contrast echocardiography (MCE) in early prediction of left ventricular functional recovery (LVFR) after acute myocardial infarction (AMI) treated with successful thrombolysis. DESIGN: LDDE and MCE using second-harmonic intermittent imaging were performed in first week after AMI. LVFR was defined as an absolute > or =5% increase in ejection fraction, from early to 6 months of follow-up by Technetium-99m-Sestamibi single-photon emission computed tomography. PATIENTS: Out of 50 patients studied, 19 evolved with LVFR (group 1) and 31 without LVFR (group 2). Regional dysfunction was detected in 103 (37%) infarcted-related segments in group 1 and in 173 (63%) segments in group 2. RESULTS: Sensitivity, specificity, positive, and negative predictive values and accuracy for detecting LVFR by LDDE were 94.7% (18/19), 87.1% (27/31), 81.8% (18/22), 96.4% (27/28), and 90% (45/50), respectively, and by MCE were 94.7% (18/19), 51.6% (16/31), 54.5% (18/33), 94.1% (16/17), and 68% (34/50). In group 1, functional improvement was observed in 86.9% (53/61) of segments with contractile reserve by LDDE and in 65.8% (52/79) of segments with microvascular perfusion by MCE. In group 2, functional improvement was observed in 78.3% (18/23) of segments with contractile reserve by LDDE and in 25.5% (25/98) of segments with microvascular perfusion by MCE. All segments without perfusion by MCE evolved without functional recovery. CONCLUSION: LDDE was an accurate predictor of late left ventricular function recovery after AMI, while MCE was sensitive and has a high negative predictive value demonstrating that microvascular perfusion is essential for LVFR.     

Detection of resting myocardial perfusion defects by SonoVue myocardial contrast echocardiography

BACKGROUND: SonoVue is a new microbubble contrast agent containing sulfur hexafluoride. We assessed the efficacy of SonoVue myocardial contrast echocardiography (MCE) to detect resting perfusion abnormalities. Methods: Nineteen adult patients with a wall motion abnormality in a screening echocardiogram were studied. Each patient received up to four bolus injections of 2.0 mL SonoVue (Bracco Diagnostics, Inc.) during echocardiographic examination using either B-mode(n = 12)or power Doppler(n = 7)imaging. Each patient also had SPECT nuclear perfusion imaging performed. Segmental assessment of myocardial perfusion from SonoVue MCE images were compared with corresponding SPECT nuclear images. RESULTS: Using B-mode imaging, the mean number of views obtained with a single SonoVue injection ranged from 1.4 to 1.9, with 2 or 3 injections required for a complete examination. Ninety-four percent of segments were scored as diagnostic. Agreement between B-mode and SPECT images was 72% for segments with a perfusion defect, 86% for normal perfusion, and 80% for segments with either perfusion defect or normal perfusion (all views combined). Using power Doppler imaging, the mean number of views obtained with a single SonoVue injection ranged from 1.0 to 1.3, with 2 to 4 injections required for a complete examination. Sixty-eight percent of segments were scored as diagnostic. Agreement between power Doppler and SPECT images was 67% for perfusion defects, 53% for segments with normal perfusion, and 59% for segments with either perfusion defect or normal perfusion (all views combined). CONCLUSIONS: SonoVue MCE has the potential to assess myocardial perfusion at rest. B-mode imaging was more accurate than power Doppler imaging when compared with SPECT nuclear imaging.     

Intravenous myocardial contrast echocardiography during angioplasty

Myocardial contrast echocardiography (MCE) using power Doppler harmonic imaging (PDHI) has been reported to document regional myocardial perfusion. Two case reports demonstrate the potential of intravenous myocardial contrast echocardiography during angioplasty.     

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.     

Qualitative and quantitative real time myocardial contrast echocardiography for detecting hibernating myocardium

Background: Real time myocardial contrast echocardiography (RTMCE) is an emerging imaging modality for assessing myocardial perfusion that allows for noninvasive quantification of regional myocardial blood flow (MBF). Aim: We sought to assess the value of qualitative analysis of myocardial perfusion and quantitative assessment of myocardial blood flow (MBF) by RTMCE for predicting regional function recovery in patients with ischemic heart disease who underwent coronary artery bypass grafting (CABG). Methods: Twenty‐four patients with coronary disease and left ventricular systolic dysfunction (ejection fraction <45%) underwent RTMCE before and 3 months after CABG. RTMCE was performed using continuous intravenous infusion of commercially available contrast agent with low mechanical index power modulation imaging. Viability was defined by qualitative assessment of myocardial perfusion as homogenous opacification at rest in ≥2 segments of anterior or ≥1 segment of posterior territory. Viability by quantitative assessment of MBF was determined by receiver‐operating characteristics curve analysis. Results: Regional function recovery was observed in 74% of territories considered viable by qualitative analysis of myocardial perfusion and 40% of nonviable (P = 0.03). Sensitivity, specificity, positive and negative predictive values of qualitative RTMCE for detecting regional function recovery were 74%, 60%, 77%, and 56%, respectively. Cutoff value of MBF for predicting regional function recovery was 1.76 (AUC = 0.77; 95% CI = 0.62–0.92). MBF obtained by RTMCE had sensitivity of 91%, specificity of 50%, positive predictive value of 75%, and negative predictive value of 78%. Conclusion: Qualitative and quantitative RTMCE provide good accuracy for predicting regional function recovery after CABG. Determination of MBF increases the sensitivity for detecting hibernating myocardium. (Echocardiography 2011;28:342‐349)     

Real time myocardial contrast echocardiography during supine bicycle stress and continuous infusion of contrast agent. Cutoff values for myocardial contrast replenishment discriminating abnormal myocardial perfusion

BACKGROUND: Myocardial contrast echocardiography (MCE) is a new imaging modality for diagnosing coronary artery disease (CAD). OBJECTIVE: The aim of our study was to evaluate feasibility of qualitative myocardial contrast replenishment (RP) assessment during supine bicycle stress MCE and find out cutoff values for such analysis, which could allow accurate detection of CAD. METHODS: Forty-four consecutive patients, scheduled for coronary angiography (CA) underwent supine bicycle stress two-dimensional echocardiography (2DE). During the same session, MCE was performed at peak stress and post stress. Ultrasound contrast agent (SonoVue) was administered in continuous mode using an infusion pump (BR-INF 100, Bracco Research). Seventeen-segment model of left ventricle was used in analysis. MCE was assessed off-line in terms of myocardial contrast opacification and RP. RP was evaluated on the basis of the number of cardiac cycles required to refill the segment with contrast after its prior destruction with high-power frames. Determination of cutoff values for RP assessment was performed by means of reference intervals and receiver operating characteristic analysis. Quantitative CA was carried out using CAAS system. RESULTS: MCE could be assessed in 42 patients. CA revealed CAD in 25 patients. Calculated cutoff values for RP-analysis (peak-stress RP >3 cardiac cycles and difference between peak stress and post stress RP >0 cardiac cycles) provided sensitive (88%) and accurate (88%) detection of CAD. Sensitivity and accuracy of 2DE were 76% and 79%, respectively. CONCLUSIONS: Qualitative RP-analysis based on the number of cardiac cycles required to refill myocardium with contrast is feasible during supine bicycle stress MCE and enables accurate detection of CAD.     

Usefulness of myocardial contrast echocardiography early after acute myocardial infarction

OBJECTIVES: (1) Evaluate wall motion and perfusion abnormalities after reperfusion therapy of the culprit lesion, (2) delineate the ability of myocardial contrast echocardiography (MCE) to evaluate the microvasculature after reperfusion, in order to distinguish between stunning and necrosis in the risk area. METHODS: We analyzed 446 segments from 28 patients, 10 normal controls (160 segments), and 18 with a first AMI (286 segments). MCE was obtained with Optison and a two-dimensional echocardiography was performed at 3 months post acute myocardial infarction (AMI). RESULTS: In the group with AMI, we analyzed 286 segments, of which 107 had wall motion abnormalities (WMA) related to the culprit artery. Two subgroups were identified: Group I with WMA and normal perfusion (50 segments, 47%) and Group II with WMA and perfusion defects (57 segments, 53%). According to the 2D echocardiogram at 3 months, they were further subdivided into: Group IA: with wall motion improvement (stunning): 18 segments, 36%, Group IB: without wall motion improvement: 32 segments, 64%, Group IIA: with wall motion improvement: 12 segments, 21%, Group IIB: without wall motion improvement (necrosis): 45 segments, 79%. CONCLUSIONS: (1) The presence of myocardial perfusion in segments with WMA immediately after AMI reperfusion therapy predicts viability in most patients. Conversely, the lack of perfusion is not an absolute indicator of the presence of necrosis. (2) Perfusion defects allow to detect patients with thrombolysis in myocardial infarction (TIMI) 3 flow and "no-reflow" phenomenon who will not show improved wall motion in the 2D echocardiogram. However, some patients with initial no-reflow could have microvascular stunning and their regional contractile function will normalize after a recovery period.