Myocardial Contrast Intensity Research Articles

Effect of Ambient Conditions on Acoustic Activation of the Perfluoropropane Droplets Within the Infarct Zone

Acoustically activated perfluoropropane droplets (PD) formulated from lipid encapsulated microbubble preparations produce a delayed myocardial contrast enhancement that preferentially highlights the infarct zones (IZ). Since activation of PDs may be temperature sensitive, it is unclear what effect body temperature (BT) has on acoustic activation (AA). We sought to determine whether the microvascular retention and degree of myocardial contrast intensity (MCI) would be affected by BT at the time of intravenous injection. We administered intravenous (IV) PD in nine rats following 60 min of ischemia followed by reperfusion. Injections in these rats were given at temperatures above and below 36.5°C, with high MI activation in both groups at 3 or 6 min following IV injection (IVI). In six additional rats (three in each group), IV PDs were given only at one temperature (<36.5°C or ≥36.5°C), permitting a total of 12 comparisons of different BT. Differences in background subtracted MCI at 3-6 min post-injection were compared in the infarct zone (IZ) and remote zone (RZ). Post-mortem lung hematoxylin and eosin (H&E) staining was performed to assess the effect potential thermal activation on lung tissue. Selective MCI within the IZ was observed in 8 of 12 rats who received IVI of PDs at <36.5°C, but none of the 12 rats who had IVI at the higher temperature (p < 0.0001). Absolute MCI following droplet activation was significantly higher in both the IZ and RZ when given at the lower BT. H&E indicated significant red blood extravasation in 5/7 rats who had had IV injections at higher BT, and 0/7 rats who had IV PDs at <36.5°C. Selective IZ enhancement with AA of intravenous PDs is possible, but temperature sensitive. Thermal activation appears to occur when PDs are given at higher temperatures, preventing AA, and increasing unwanted bioeffects.

Myocardial Perfusion Imaging Using Contrast Echocardiography

Microbubbles are an excellent intravascular tracer, and both the rate of myocardial opacification (analogous to coronary microvascular perfusion) and contrast intensity (analogous to myocardial blood volume) provide unique insights into myocardial perfusion. A strong evidence base has been accumulated to show comparability with nuclear perfusion imaging and incremental diagnostic and prognostic value relative to wall motion analysis. This technique also provides the possibility to measure myocardial perfusion at the bedside. Despite all of these advantages, the technique is complicated, technically challenging, and has failed to scale legislative and financial hurdles. The development of targeted imaging and therapeutic interventions will hopefully rekindle interest in this interesting modality.

Myocardial blood flow assessment in cardiac amyloidosis using myocardial contrast echocardiography

Cardiac amyloidosis (CA) patients may present with angina and coronary syndromes. Cardiac biomarkers are chronically elevated in some cases. Many proceed with coronary investigation which often reveals angiographically patent vessels. An explanation for their presentation is thought to be due to microvascular amyloid deposition resulting in microvascular dysfunction. We performed vasodilator myocardial contrast echocardiography (MCE) on a patient with CA to assess myocardial blood flow reserve (MBFR). She previously had patent epicardial coronary arteries on coronary angiography and a normal dobutamine stress echocardiogram. Real-time MCE was performed according to an established protocol using a commercial ultrasound machine and contrast agent. Images were recorded in the 3 apical views with low-power settings at a mechanical index of 0.1. Flash-impulse imaging at a high mechanical index (1.0) was performed to achieve complete myocardial bubble destruction, after which 10 end-systolic frames were recorded digitally in each view. Imaging was repeated after dipyridamole infusion. Background-subtracted plots of peak myocardial contrast intensity (representingmyocardial blood volume A) versus pulsing intervals (representing time) were constructed by QLab software to fit the monoexponential function conventional equation: y=A (1−e− t). From these plots, the slope of the replenishment curve was determined (representing myocardial blood velocity ). Per segment, the product of A and yielded rest MBF and post-dipyridamole MBFs (stress MBF), respectively. MBFR was calculated as the ratio of peak MBF to resting MBF. The results show a marked reduction in MBFR. This supports the hypothesis of microvascular dysfunction and adds to our pathophysiological understanding of this challenging condition.

Experimental study of relationship on myocardial perfusion, regional contractile function and cell apoptosis in stunned myocardium by myocardial contrast echocardiography with computer-aided technique

Objective To evaluate a new computer-aided technique applicable for myocardial contrast echocardiography(MCE) to quantitate automatically calibrated myocardial contrast intensity(CD and to test the feasibility of calibrated CI in assessing myocardial perfusion. To analyze the relationship on myocardial perfusion,regional contractile function and cell apoptosis in stunned myocardium. Methods According to coronary occlusion and reperfusion at different times, rabbits were divided into three groups: 15 min occlusion/30min reperfusion (group Ⅰ ),30 min occlusion / 60min reperfusion (group Ⅱ ) and 120 min occlusion / 60min reperfusion (group Ⅲ ). MCE was performed on all rabbits at baseline,occlusion and after reperfusion,and its images were analyzed by a new computer-aided technique. Myocardial calibrated CI of each segment was measured automatically by software. Percentage wall thickening (WT) of each risk segment at each stage were also measured by echocardiography. The apoptotic index(AI) in regional left myocardial dysfunction was calculated by terminal deoxynucleotidyl transferease-mediated biotinylated deoxyuridine triphosphate nick end labeling(TUNEL ). Results (1) During occlusion, WT in the areas at risk decreased to zero or negative and the calibrated CI values were significantly lower than those at baseline ( P ＜0.01 ). After reperfusion, WT in all risk segment remained depressed, but calibrated CI significantly improved in group Ⅰ and Ⅱ while those remained unchanged in group Ⅲ. (2)AI in risk myocytes were (13. 70 ± 5.48 ) %, (36.25 ± 5.55 ) % and ( 62.06 ± 6. 70 ) %, respectively, both statistically significant difference between the two groups ( P ＜0.05 or P ＜ 0.01 ). AI were negatively correlated to WT and calibrated CI ( r = - 0. 87 and r = - 0. 77, P ＜0.05). Conclusions MCE with computer-aided technique can assess quantitatively myocardial perfusion and regional contractile function. Short-term ischemiareperfusion does not cause myocardial necrosis, but it will lead to myocardial cell apoptosis and the phenomenon of myocardial stunning. Prolonged ischemia, even if given sufficient reperfusion, can lead to apoptosis and necrosis simultaneously. Key words: Echocardiography; Microbubbles; Image processing,computer-aided; Myocardial reperfusion; Apoptosis

Angiotensin II Receptor Blocker, Valsartan, Increases Myocardial Blood Volume and Regresses Hypertrophy in Hypertensive Patients

Although a reduction in myocardial blood volume (MBV), an in vivo index of the myocardial microvasculature, measured by myocardial contrast echocardiography in patients with hypertension (HT), can be demonstrated, it is still unknown whether a decreased MBV can be improved by antihypertensive treatment. Eleven HT patients (mean age 58 years, 7 men) with left ventricular hypertrophy (LVH) and 10 age- and sex-matched normal controls were studied. Harmonic power Doppler images were acquired at end-diastole of every 6(th) beat and MBV was calculated as 10(X/10)x100%, where X (dB) is myocardial contrast intensity minus the contrast intensity of the adjacent intracavity blood pool. Baseline blood pressure (BP) and left ventricular mass index (LVMI) in the HT patients were higher and MBV was lower than in the controls (2.52 +/-0.37% vs 3.31 +/-0.61%, P<0.01). MBV did not correlate with mean BP, but was inversely correlated with LVMI (r=0.61, P<0.01). After treatment with valsartan for 6 months, LVMI significantly decreased and MBV increased (2.72 +/-0.26%, P<0.05 vs baseline) in the patients with HT. There was a significant inverse correlation between the changes in MBV and those of LVMI (r=0.62, P<0.05), but not between MBV and mean BP. Valsartan, an angiotensin II receptor blocker, corrected the decreased MBV in association with regression of LVH in patients with HT.

Abstract 2085: Increased Regional Coronary Vascular Resistance During Hyperemia in Hypertrophic Cardiomyopathy Is Associated with Reduced Myocardial Blood Volume

Introduction: In patients with hypertrophic cardiomyopathy ( HCM ), myocardial blood flow ( MBF ) is decreased during hyperemia because of high coronary vascular resistance. Recently myocardial blood volume ( MBV ) can be estimated in vivo using myocardial contrast echocardiography ( MCE ) with the compensation for acoustic field inhomogeneity. The relationship between MBV and coronary resistance, however, has not been investigated. We thus assessed the hypothesis that increased regional coronary vascular resistance during hyperemia in HCM is associated with reduced MBV. Methods: In 13 patients with HCM ( H , 53±16 years) with asymmetric septal hypertrophy and 9 normal volunteers ( N , 54±11 years), MCE was performed under infusion of Levovist at rest and during hyperemia induced by ATP. Apical 4-chamber views of intermittent harmonic power Doppler imaging were acquired at end-diastole of every sixth beat. MBV was calculated as 10 X/10 ×100%, where X was myocardial contrast intensity minus contrast intensity of the adjacent intracavity blood pool in dB. 15 O-water PET was performed to measure regional MBF. These parameters were measured in the interventricular septum ( IVS ) and LV posterolateral ( PL ) wall. Regional coronary vascular resistance was calculated as (mean blood pressure)/MBF. Results: Wall thickness was significantly greater in H than in N (IVS: 19±4 vs 10±1 mm, p&lt;0.0001; PL: 10±1 vs 9±1 mm, p&lt;0.05). MBV of IVS was lower in H than in N (rest: 2.1±0.7 vs 3.5±1.1%, p&lt;0.01; hyperemia: 2.1±1.3 vs 4.3±1.7%, p&lt;0.01), whereas MBV of PL wall did not differ between groups. Coronary resistance at rest did not differ between groups, but the resistance during hyperemia was significantly greater in H than in N (IVS: 59±16 vs 31±14 mmHg·min·g·ml −1 , p&lt;0.001; PL: 40±10 vs 30±11 mmHg·min·g·ml −1 , p&lt;0.05). Coronary resistance at rest did not correlate with MBV, whereas that during hyperemia inversely correlated with MBV during hyperemia (r=−0.77, p&lt;0.0001) as well as MBV at rest (r=−0.65, p&lt;0.0001). Conclusions: Increased coronary vascular resistance during hyperemia in HCM was significantly associated with reduced MBV. MCE is useful for assessing the dynamic function of coronary circulation in the clinical setting.

Myocardial contrast echocardiography accurately reflects transmurality of myocardial necrosis and predicts contractile reserve after acute myocardial infarction

Both myocardial contrast echocardiography (MCE) and cardiovascular magnetic resonance (CMR) can identify myocardial necrosis after acute myocardial infarction (AMI). However, transmural extent of infarction (TEI) correlates of myocardial perfusion by MCE after AMI are unknown. We sought to ascertain the ability of MCE to (1) predict TEI as defined by contrast-enhanced CMR and (2) to compare the relative accuracy of these techniques to predict contractile reserve late after AMI. MCE and CMR were performed in 42 patients with AMI 7 to 10 days after thrombolysis. Contractile reserve with low-dose dobutamine was evaluated 12 weeks after revascularization. Both qualitative (myocardial contrast intensity) and quantitative MCE [peak contrast intensity, microbubble velocity (beta), and myocardial blood flow] showed a significant (P < .0001) inverse relationship with increasing TEI. However, beta was the single best predictor of TEI (P = .002). Both qualitative MCE and CMR predicted contractile reserve similarly (area under receiver operating characteristic curve were 0.84 and 0.80, respectively). Qualitative and quantitative MCE parameters as well as CMR correlated significantly with the degree of contractile reserve (P < .001). Multiple logistic regression analysis using clinical, electrocardiographic, MCE, and CMR parameters showed that both MCE (OR = 0.03, 95% CI 0.01-0.10, P < .001) and CMR (OR = 0.11, 95% CI 0.04-0.26, P < .001) are independent predictors of contractile reserve. The most discriminative quantitative parameters for prediction of contractile reserve were microbubble velocity (P < .001) and myocardial blood flow (P = .001) assessed by MCE. MCE reflects the transmural extent of AMI as assessed by CMR. Both techniques predict contractile reserve.

Myocardial microvascular abnormalities and left ventricular strain rate as the new predictors of cardiac events in patients with dilated cardiomyopathy

Hypothesis: We hypothesized that myocardial microvascular abnormalities assessed by myocardial contrast echocardiogrpahy (MCE) and altered strain rate (SR) parameters could be predicted to cardiac events in patients with dilated cardiomyopathy (DCM). Methods: Thirty-four patients with DCM were enrolled. MCE was performed with SONOS 5500 (Philips Medical Systems) and peak myocardial contrast intensity (PMCI) was measured as the value of microvascular integrity. Color tissue Doppler imaging was performed and strain or SR parameters were estimated. In addition, LV ejection fraction (EF), LV end-diastolic volume index (EDVI), transmitral E-wave decerelation time (DT) and mitral annular velocity during early diastole (Em) were also calculated. Cardiac events were defined as cardiac death and hospitalization for worsening heart failure. Results: PMCI was closely associated with systolic SR in patients with DCM (r = 0.688, p = 0.0011). In this study population, 7 patients had major cardiac events. Univariate analysis showed that PMCI, systolic strain and SR, EF, EDVI, and Em were significantly related to cardiac events in patients with DCM (p < 0.05 for all). According to the multivariate analysis, PMCI and systolic SR were the independent predictors for cardiac events in such patients (p = 0.0098 and p = 0.0072, respectively). Conclusion: Our study suggests that the PMCI and systolic SR may be the new powerful predictors for cardiac events in patients with DCM.

Myocardial microvascular abnormalities observed by intravenous myocardial contrast echocardiography in patients with hypertrophic cardiomyopathy

We tested the hypothesis that myocardial microvascular abnormalities occur and are influenced by clinical features in 30 patients with hypertrophic cardiomyopathy (HC) using intravenous myocardial contrast echocardiography. Patients with HC were subdivided into 3 groups: nonobstructive HC (n = 12), obstructive HC (n = 10), or HC with systolic dysfunction and heart failure (n = 8). In patients with nonobstructive HC and obstructive HC, subendocardial peak myocardial contrast intensity at the mid-septal area was significantly decreased and the transmyocardial difference of peak myocardial contrast intensity between subendocardial and periendocardial regions at the mid-septal area was significantly related to regional wall thickness. Reduced peak myocardial contrast intensities at the mid-septal subendocardial and periendocardial regions were observed in patients with HC and heart failure. Our study indicates that subendocardial microvascular abnormalities during end-systole may be associated with severity of regional myocardial hypertrophy in patients with nonobstructive HC and obstructive HC. In addition, progressive microvascular damage may occur in patients with HC and heart failure.

Myocardial contrast echocardiography with a new calibration method can estimate myocardial viabilityin patients with myocardial infarction

ObjectivesWe have developed a novel calibration technique applicable for myocardial contrast echocardiography (MCE). We assessed the value of this technique in the recognition of myocardial infarction (MI) and its spatial extent, and we also performed a validation study in normal subjects. BackgroundThe heterogeneity of contrast intensity (CI) among myocardial segments limits the clinical use of MCE. MethodsWe performed MCE with a slow-bolus injection of Levovist and recorded end-systolic harmonic power Doppler images at intervals of four heart beats in 15 normal volunteers and 30 patients with MI. We divided the left ventricular (LV) wall into 12 segments and placed the region of interest in the subendocardial region in each segment and in the adjacent LV cavity. We measured calibrated CI (dB) by subtracting the cavity CI from myocardial CI. ResultsThe mean intersegmental difference in myocardial CI was 15.8 dB at baseline, whereas it was reduced to 6.3 dB after calibration (p < 0.01). Calibrated CI was higher in the kinetic segments than in the akinetic segments (−14.5 ± 2.3 dB [range −18.7 to −9.9 dB] vs. −22.5 ± 2.6 dB [−27.8 to −17.7 dB], p < 0.001), and −18.0 dB was the optimal cutoff point to discriminate these from each other. Color-coded mapping of calibrated CI may identify the spatial extent of persistently akinetic myocardium as areas of calibrated CI of ≤−18.0 dB. ConclusionsThis new calibration method reduces the intersegmental difference in CI in normal subjects. Calibrated CI provides an estimate of persistently akinetic myocardium in patients with MI, and its color-coded mapping is comprehensive and identifies the spatial extent of MI.

Quantitative myocardial contrast echocardiography for prediction of Thrombolysis In Myocardial Infarction flow in acute myocardial infarction

Clinical evaluation of arterial patency in acute ST-elevation myocardial infarction (STEMI) is unreliable. We sought to identify infarction and predict infarct-related artery patency measured by the Thrombolysis In Myocardial Infarction (TIMI) score with qualitative and quantitative intravenous myocardial contrast echocardiography (MCE). Thirty-four patients with suspected STEMI underwent MCE before emergency angiography and planned angioplasty. MCE was performed with harmonic imaging and variable triggering intervals during intravenous administration of Optison. Myocardial perfusion was quantified offline, fitting an exponential function to contrast intensity at various pulsing intervals. Plateau myocardial contrast intensity (A), rate of rise (β), and myocardial flow (Q = A × β) were assessed in 6 segments. Qualitative assessment of perfusion defects was sensitive for the diagnosis of infarction (sensitivity 93%) and did not differ between anterior and inferior infarctions. However, qualitative assessment had only moderate specificity (50%), and perfusion defects were unrelated to TIMI flow. In patients with STEMI, quantitatively derived myocardial blood flow Q (A × β) was significantly lower in territories subtended by an artery with impaired (TIMI 0 to 2) flow than those territories supplied by a reperfused artery with TIMI 3 flow (10.2 ± 9.1 vs 44.3 ± 50.4, p = 0.03). Quantitative flow was also lower in segments with impaired flow in the subtending artery compared with “normal” patients with TIMI 3 flow (42.8 ± 36.6, p = 0.006) and all segments with TIMI 3 flow (35.3 ± 32.9, p = 0.018). An receiver-operator characteristic curve derived cut-off Q value of <11.3, representing impaired myocardial flow, was 73% sensitive and 67% specific for TIMI <3 flow at angiography. Thus, qualitative MCE identifies patients with STEMI but provides no information regarding infarct-related artery patency, whereas quantitative MCE can predict impaired flow in patients with acute STEMI.

A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model

ObjectivesWe investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation. BackgroundThe myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography. MethodsFourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD. ResultsIn the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01). ConclusionsMyocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Real-time assessment of myocardial perfusion during balloon angioplasty of the left anterior descending coronary artery

Balloon occlusion and release during elective percutaneous coronary intervention (PCI) provides a unique opportunity to study dynamic temporal alterations in myocardial perfusion in a controlled setting. These changes in flow and volume mimic those that occur during presentation with, and successful therapy of, ST-segment elevation acute myocardial infarction (AMI). Eleven patients underwent myocardial contrast echocardiography (MCE) using a continuous infusion of Definity at baseline, during coronary occlusion, and during reactive hyperemia immediately after balloon deflation. Fifty separate flow state sequences were acquired, and off-line analysis was performed to determine myocardial contrast intensity within a region of interest in the distribution of the left anterior descending artery (LAD). A reader blinded to flow state also performed qualitative evaluation (perfusion or lack of perfusion). Quantitative analysis demonstrated significant differences in myocardial contrast intensity by flow state (p = 0.0001 for occlusion vs reperfusion). Qualitative assessment demonstrated a high rate of correct classification (92%). Real-time myocardial perfusion assessment using MCE accurately differentiates coronary occlusion and reactive hyperemia in humans by qualitative and quantitative assessment. This technique may be clinically useful in assessing the efficacy of thrombolytic therapy in ST-segment elevation AMI and in clinical trial assessment of new drugs and devices aimed at limitation of infarct size.

Quantitative parameters of myocardial perfusion with contrast echocardiography in human beings: Influence of triggering mode

To facilitate quantitation of myocardial contrast echocardiography (MCE) in human beings, dual- or triple-triggered flash imaging has been advocated. However, the effect of this modality on quantitative blood-flow parameters of MCE is not known. Accordingly, MCE was quantitated in 71 myocardial regions of 22 patients (age: 57 ± 16 years) during continuous infusion of Optison (12-18 mL/h). Two sets of images with end-systolic gating (1:1, 1:2, 1:3, 1:4, 1:6, and 1:8) from the apical 4-chamber view were acquired: single and dual triggering for the first 15 patients; and single and triple triggering for the other 7 patients. During gated imaging, MCE of the first, second, and third frame were quantitated. Curves of intensity versus pulsing intervals were fitted to an exponential function:y = A (1-e−βt). Where β is myocardial blood velocity or the rate of rise of myocardial contrast intensity (MCI), and A is myocardial blood volume or the plateau of MCI reached. Continuous imaging, and the second and third frame in 1:1 gating only, provided similar intensity to precontrast imaging. Beyond 1:1 gating, MCI of the second frame in dual triggering mode gradually increased with incremental pulsing interval. This was still present but less pronounced in triple triggering. During dual and triple triggering, a lower β was observed compared with single triggering. Application of image subtraction with the flash procedure further decreased β, A, and the A*β product, a quantitative parameter of blood flow by MCE. Thus, flash subtraction imaging alters the quantitative parameters of myocardial blood velocity and flow derived from MCE. Continuous imaging, and the second or third frame in flash imaging at 1:1 gating only, result in MCI similar to precontrast imaging and can be used for background subtraction to quantitate MCE parameters. (J Am Soc Echocardiogr 2002;15:1432-9.)

Cyclic variation of myocardial signal intensity in real-time myocardial perfusion imaging

Background: The presence of cyclic intensity variation during real-time myocardial perfusion imaging (RTPI) has been controversially discussed. We investigated whether cyclic intensity variation is systematically found during RTPI and whether such variations are related to regional functional parameters. Methods: Intraoperative RTPI were obtained in 12 pigs before, during, and after left descending coronary artery occlusion with 60 mL/h SonoVue infusion. Furthermore, RTPI was performed in 14 patients after slow bolus injection of 0.7 mL of Optison. Instantaneous regional systolic to diastolic (S/D) myocardial intensity ratios were calculated after high mechanical index bubble destruction. S/D ratios were correlated with A- and β-values, and fractional area shortening. Results: Systematic cyclic S/D changes were present in both experimental settings showing significantly higher systolic values (animals, S/D 1.28 ± 0.44; patients, S/D 1.25 ± 0.7). Cyclic S/D variation was not related to fractional area shortening, or A- or β-values (all r < 0.3, not significant). Conclusion: Consistent cyclic changes in myocardial contrast intensity can be measured both in intraoperative animals and in patients, showing higher systolic values. S/D ratios are not related to regional functional parameters. (J Am Soc Echocardiogr 2002;15:1425-31.)

Myocardial cavitational activity during continuous infusion and bolus intravenous injections of perfluorocarbon-containing microbubbles

The 20-MHz component of broadband noise from inertial cavitation within the anterior myocardium of an open-chest dog was recorded during intravenous infusions or injections of perfluorocarbon-containing microbubbles during insonation with a 1.7-MHz harmonic transducer. Intramyocardial cavitational activity was evident even at a mechanical index of 0.2, but it increased significantly as frame rate and mechanical index were increased. The amount of myocardial contrast intensity produced by the microbubbles was increased by variables that reduced cavitational activity (eg, reducing frame rate to 1 every cardiac cycle or decreasing mechanical index). At a mechanical index of 0.2, myocardial contrast could still be observed at 10-Hz frame rates. These results confirm that intramyocardial cavitational activity is present during ultrasound imaging of microbubbles; imaging techniques that reduce cavitational activity increase the magnitude of myocardial contrast. (J Am Soc Echocardiogr 2001;14:618-25.)

MYOCARDIAL CONTRAST ENHANCEMENT AFTER IV OPTISON[trade mark sign] FOR INTRAOPERATIVE ECHOCARDIOGRAPHY DURING CARDIAC SURGERY

Introduction. Since 1998, Optison[trade mark sign], a venous ultrasound contrast agent of albumin micro-spheres filled with octafluoropropane, has been available to improve left ventricular (LV) endocardial border delineation. Optison[trade mark sign] was used to show myocardial perfusion in dogs. Contrast agents injected arterially have been used in humans to show myocardial perfusion. The noninvasive demonstration of myocardial perfusion during cardiac surgery with transesophageal echocardiography (TEE) would be helpful in distinguishing stunned but perfused from ischemic myocardium. Methods. 23 patients (pts) undergoing valvular surgery with normal coronary anatomy were studied. Two different echo systems equipped for on-line measurement of reflected ultrasound energy in a user defined region of interest (ROI) [Acuson Aspen[trade mark sign] (AA) and Hewlett Packard Sono 5500[trade mark sign] (HP)] were used to measure contrast intensity. In a transgastric shortaxis view of the LV, the ROI was placed in the inferior wall, and a bolus of 0.3 ml of Optison[trade mark sign] was injected into a central vein while contrast intensity was measured and recorded. Imaging was triggered by electrocardiography and ventilation interrupted to eliminate motion artifacts during image acquisition. Results. In 2 of 30 injections in 11 pts imaged with the AA system, increases in myocardial contrast intensity were seen in 2 pts. In 12 of 42 injections in 12 pts imaged with the HP system, increases in myocardial contrast intensity were seen in 5 pts, with the most dramatic response shown (Figure 1). In 3 of these pts, effects were repeatable in multiple injections, while one patient showed increased myocardial contrast intensity only during a dobutamine infusion. 16 pts (9 imaged with AA, 5 with HP) showed no contrast effect on multiple contrast injections.Figure 1Discussion. We inconsistently detected increased myocardial contrast intensity in the LV inferior wall after IV injection of Optison[trade mark sign]. This effect was not repeatable in all pts and was never seen in others. Some of the differences seen might be due to the methods used by the echo systems to measure and process reflected ultrasound energy into data. Also, in 6 of 11 pts imaged with the AA system we triggered at every heart beat, which might have caused accelerated destruction of microspheres, thereby unabling us to measure contrast effect. All other studies were triggered at every 4th heart beat. More study and technical advances are needed to make myocardial contrast echocardiography a reliable, reproducible technique for the intraoperative setting.

Correlation Between Quantitative Angiographic Lesion Severity and Myocardial Contrast Intensity During a Continuous Infusion of Perfluorocarbon-Containing Microbubbles

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = −0.89 for both, p < 0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography. (J Am Soc Echocardiogr 1998;11:702-10.)

Detection of Perfusion Defects During Coronary Occlusion and Myocardial Reperfusion After Thrombolysis by Intravenous Administration of the Echo-Enhancing Agent BR1

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (IV) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 μm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 ± 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused IV; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 ± 16 to 147 ± 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 ± 12 to 21 ± 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% ± 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres ( r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the IV administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.(J Am Soc Echocardiogr 1998;11:169-80.)

Benefits of reducing the cardiac cycle–triggering frequency of ultrasound imaging to increase myocardial opacification with FSO69 during fundamental and second harmonic imaging

Background: Recent work has shown significant enhancement in myocardial contrast intensity with brief ultrasound pulsing gated to a discrete portion of the cardiac cycle over conventional 30 Hz imaging. We hypothesized that limiting ultrasound imaging to less than every cardiac cycle would further intensify the myocardial echo-contrast effect. We therefore sought to determine the best pulsing frequency for ultrasound imaging to achieve optimal myocardial perfusion after the intravenous administration of FSO69 using fundamental and second harmonic imaging. Methods and Results: In 13 male mongrel dogs, myocardial contrast opacification was determined while varying the cardiac cycle–triggering frequency of ultrasound imaging after intravenous injections of FSO69. Resulting myocardial echo-contrast intensities with a cardiac cycle–triggering frequency of every beat during end-diastole were compared with those with a cardiac cycle–triggering frequency of every third and fifth beat. Myocardial opacification, measured by background-subtracted peak intensity and visual scoring, was significantly greater when ultrasound imaging was triggered to every third and fifth beats compared with every beat. These benefits were seen with imaging in both the fundamental and second harmonic modes. Optimal myocardial opacification with FSO69 was achieved with injections as low as 0.1 ml, a dose that produced significant acoustic shadowing in only 24% of the injections. The degree of myocardial opacification was not significantly affected when the images were acquired during end-systole or end-diastole. Conclusions: Electrocardiogram-gated ultrasound imaging to every third or fifth cardiac cycle greatly improves myocardial opacification compared with imaging each cardiac cycle. This benefit was increased twofold to threefold with the use of second harmonic imaging as compared with fundamental imaging. (J Am Soc Echocardiogr 1997;10:602-7.)