Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results

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

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

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

Harmonic Power Doppler Contrast Echocardiography: Preliminary Experimental Results

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

Contrast-Enhanced Harmonic Color Doppler for Left Ventricular Opacification: Improved Endocardial Border Definition Compared to Tissue Harmonic Imaging and Optimization of Methodology in Patients with Suboptimal Echocardiograms

OBJECTIVES: This study compared the efficacy of contrast-enhanced harmonic color Doppler (C-HCD) and tissue harmonic imaging (THI) for left ventricular endocardial border delineation and explored the optimal methodology of C-HCD in patients with suboptimal echocardiograms. BACKGROUND: The value of C-HCD in improving endocardium remains unknown. Effects of harmonic velocity-encoded color Doppler (HVD) and harmonic power Doppler (HPD) as well as contrast administration and image acquisition modalities on left ventricular opacification (LVO) have not been established. METHODS: One hundred (50 HVD, 50 HPD) patients with suboptimal echocardiograms during conventional fundamental echocardiography were studied with THI and C-HCD using Levovist. Each patient underwent different random contrast administration and image acquisition modalities. Endocardial border definition score index (EBDI), blooming artifacts, contrast destruction, and salvage of suboptimal echocardiograms were calculated in each patient after contrast enhancement. RESULTS: EBDI improved from 2.05 +/- 0.61 in THI to 2.73 +/- 0.48 in HVD, and 1.98 +/- 0.73 in THI to 2.69 +/- 0.51 in HPD (both P < 0.001). The conversion of a nondiagnostic image from fundamental echocardiography to an optimal diagnostic image was 33 (33%) patients in THI compared to 77 (77%) patients in C-HCD (P < 0.001). Blooming artifacts were seen more commonly in HVD than HPD, intermittent than continuous image acquisition, and bolus than infusion administration (all P < 0.001). There was less contrast destruction in intermittent compared with continuous image acquisition (P < 0.001). Contrast destruction was similar in HVD and HPD, bolus and infusion injection of contrast. The highest salvage rate of a nondiagnostic image from THI to an optimal diagnostic image was 45.5% and 42.4% in HPD mode, with intermittent image acquisition during bolus and infusion contrast administrations. CONCLUSIONS: C-HCD seems more effective in demonstrating improved endocardial border definition compared to THI. HPD has less blooming artifacts compared with HCD. The optimal method for LVO was to use HPD with intermittent image acquisition during bolus or infusion administration of Levovist.     

Identification of cardiac abnormal structures with harmonic power Doppler contrast echocardiography

We describe two cases in which echocardiographic image enhancement with an intravenous contrast agent using harmonic power Doppler (HPD) imaging established the diagnosis of abnormal structures in the left ventricle (LV).     

Real-Time Contrast Echo Assessment of Myocardial Perfusion at Low Emission Power: First Experimental and Clinical Results Using Power Pulse Inversion Imaging

Power pulse inversion (PPI) has been developed for echocontrast specific imaging in order to reduce destruction of microbubbles. The purpose of this study was to evaluate PPI for real-time contrast echocardiography. Therefore, in vitro studies in a physiological flow-phantom and clinical examinations in patients with coronary artery disease were performed. The in vitro rersults of this study indicate that PPI allows real-time imaging at low emission power and is almost nondestructive to contrast microbubbles of Definity. At this low emission power a strong linear relationship between the dosage of the contrast agent and the resulting PPI signal intensity was found (R = 0.998, p < 0.001). In the clinical examinations real-time imaging using low mechanical index PPI resulted in strong myocardial signals and a complete filling of the cavities indicating absence of bubble destruction. Most striking was the ability of PPI to display myocardial thickening and wall motion simultaneously with the assessment of myocardial contrast replenishment following ultrasound induced bubble destruction by high power frames. We conclude that PPI allows nondestructive contrast imaging both in experimental and clinical settings. Therefore, real-time imaging of myocardial perfusion and real-time assessment of contrast replenishment following ultrasound induced destruction of microbubbles is feasible. Moreover, PPI allows simultaneous assessment of perfusion and myocardial function.     

Complementary Roles of Transthoracic Two-Dimensional Color Doppler Imaging and Myocardial Contrast Echocardiography in Diagnosis of Endomyocardial Fibrosis

Endomyocardial fibrosis (EMF) is a rare progressive restrictive cardiomyopathy of unknown etiology that mainly presents with heart failure. The presence of a small ventricle with obliteration of the apex and a large atrium are two-dimensional echocardiographic findings that are highly suggestive of EMF. Cardiac magnetic resonance with delayed enhancement allows detection of subendocardial fibrosis with good histopathological correlation, providing a noninvasive modality for diagnosing EMF. We herein report a case of EMF in which the complementary role of two-dimensional color Doppler imaging and myocardial contrast echocardiography proved to be useful in the diagnosis of this clinical entity, which was later confirmed by cardiac magnetic resonance, surgery, and histopathology.     

Power Doppler myocardial contrast echocardiography using an improved multiple frame triggered Harmonic Angio technique

Although B-mode harmonic, intermittent-triggered myocardial contrast echocardiography (MCE) is a well-established technique, a variety of MCE techniques have been introduced recently to improve myocardial opacification. One such technique uses a power Doppler method in conjunction with multiple frame triggering (MFT), but has been limited by nonuniform microbubble destruction and blooming as well as motion artifacts. Utilizing two different contrast agents, Definity and Optison, we tested the feasibility of an improved version of Harmonic Angio MFT that utilizes a lower transmit frequency, reduced packet size, and more stringent wall filter in normal volunteers and in patients with known perfusion defects. The results showed that Harmonic Angio MFT produced fill frames with readily visible opacification and destruction frames with little visible opacification. The patterns of opacification also correlated with the expected perfusion patterns in both groups of subjects. Thus, Harmonic Angio MFT appears to be a promising new MCE technique.     

Novel Application of Tissue Doppler Imaging

Tissue Doppler imaging was used with transthoracic and transesophageal echocardiography to determine its clinical usefulness beyond visualization of ventricular wall motion. Thirteen novel applications were found: acoustically difficult transthoracic studies, thrombus, mitral chordal motion, shunt detection using saline contrast, spontaneous echo contrast, intra-aortic balloon pump position and function, endocarditis (prosthetic and native), valve strands (prosthetic and native), mobile aortic atheroma, prosthetic valve motion, aortic valve motion in the presence of a calcified aortic annulus, systolic anterior motion of the mitral valve, and cardiac tumors. Tissue Doppler imaging directly affected the ability to make difficult diagnostic decisions with increased confidence and reduced the need for additional studies.     

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

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

经胸超声心动图声学造影与经颅多普勒超声声学造影同步试验对卵圆孔未闭的诊断价值

目的:探讨经胸超声心动图声学造影(cTTE)与经颅多普勒超声声学造影(cTCD)同步试验对卵圆孔未闭(PFO)的诊断价值。方法:选取我院疑似PFO患者769例,其中在静息和Valsalva动作下行cTTE 298例、cTTE与cTCD同步试验471例。以经食道超声心动图(TEE)为PFO的诊断标准,分析cTTE与cTCD同步试验对PFO的诊断价值。结果:共纳入769例患者,其中Valsalva动作下PFO阳性263例(34.2%)。298例患者行cTTE检查,静息时PFO阳性30例(10.1%),Valsalva动作下PFO阳性104例(34.9%),Valsalva动作下PFO阳性率较静息时显著提高(P<0.05)。471例患者行cTTE与cTCD同步试验,静息时PFO阳性50例(10.6%),Valsalva动作下PFO阳性159例(33.7%),Valsalva动作下PFO阳性率较静息时显著提高(P<0.05)。以TEE为PFO确诊标准,Valsalva动作下cTTE诊断PFO的准确性为87.5%(40/44),cTTE与cTCD同步实验诊断PFO的准确性为95.2%(40/42)。结论:cTTE与cTCD同步试验能提高PFO的诊断价值,尤其是Valsalva动作下PFO阳性率明显提高;cTTE与cTCD同步试验较cTTE诊断准确性提高。     

Power Doppler dual-frame triggering of myocardial contrast echocardiography: a quantitative video intensity analysis

AIM: The purpose of this study was to define the pattern of myocardial contrast observed during triggered dual-frame power Doppler imaging. METHODS AND RESULTS: Ten patients with no previous history of myocardial infarction underwent a continuous intravenous infusion of Optison at 0.5 ml/min. Triggered, sequential dual-frame power Doppler imaging was performed from an apical four-chamber view using a prototype Acuson Sequoia imaging system. The average triggering interval was once every four cardiac cycles, and the average interval between sequential frames was 50 msec. Video intensity analysis was performed in five myocardial regions of interest, and the percent decrease in video intensity of the destruction frames in each region of interest was determined by subtracting the destruction frame video intensity from the fill frame video intensity. The percent decrease in video intensity varied significantly by myocardial location (P < 0.001), with greater destruction seen in the apical than in the basal regions. CONCLUSION: This preliminary study demonstrates that power Doppler dual-frame triggering produces nonuniform decreases in video intensity, which likely represent nonuniform microbubble destruction. These results have important implications for the interpretation of myocardial perfusion patterns using this technique.     

Assessment of regional myocardial hypoperfusion with myocardial contrast echocardiography using intravenous bolus application in patients with acute chest pain: a double case report.

Myocardial contrast echocardiography using power Doppler harmonic imaging is able to document myocardial hypoperfusion. Two case reports demonstrate the potential of intravenous bolus application of microbubbles in patients with acute chest pain due to myocardial ischaemia to detect regional low flow conditions. The case reports will focus on the necessity to present Doppler intensity kinetics by Doppler intensity vs time plots or coloured M-modes to present the data more objectively. In addition, the hypoperfusion detected with myocardial contrast echocardiography via bolus injection of microbubbles can only be proven by changes of regional perfusion between repetitive myocardial contrast echocardiography measurements or by additional perfusion analysis, e.g. by scintiscanning.     

Estimation of vasodilator response by analysis of Doppler intensity kinetics with myocardial contrast echocardiography using an intravenous standardized bolus administration.

HYPOTHESIS: Myocardial perfusion can be analyzed by the first pass of Doppler intensity (DI) signals in the myocardium by myocardial contrast echocardiography with triggered power Doppler harmonic imaging (PDHI). METHODS AND RESULTS: DI versus time plots during 1:1 triggering was acquired during a mechanically standardized intravenous bolus application of Levovist (400 mg ml(-1); 3 ml min(-1)) at rest and during vasodilator stress with dipyridamole. Data were analyzed in 21 patients (pts) with normal coronary arteries and in 6 pts with left anterior descending artery (LAD) stenosis. Transthoracic distal LAD-flow velocities could be determined in 7 normal pts. At stress the DI wash-in rate and the DI plateau increased (3.14+/-0.3 versus 5.06+/-0.4 DI s(-1); 24.6+/-2.5 versus 30.8+/-1.8 DI, respectively). To analyze the effect of heart rate on the DI versus time plots investigations were performed in 7 additional controls at rest and during rapid pacing. Heart rates below 100 bpm did not disturb the DI kinetics at 1:1 triggering. CONCLUSIONS: Myocardial perfusion can be assessed by the analysis of the first pass DI kinetics using Levovist. The estimation of vasodilator response by PDHI seems to be an alternative to the determination of coronary flow reserve.     

Harmonic imaging: echocardiographic enhanced contrast intensity and duration

The intensity and duration of contrast effect within the left ventricular cavity after an intravenous bolus of Levovist Injection were observed with both harmonic and fundamental imaging in nine patients with known or suspected coronary artery disease. Contrast intensity was assessed by a qualitative grading system (0, none; 1, weak; 2, moderate; 3, good) and by videodensitometric analysis of pixel intensity. Duration of left ventricular contrast effect was determined by measuring time from the initial visual appearance of contrast agent to its disappearance. The mean increase in pixel intensity within the left ventricular cavity from precontrast to peak contrast was significantly greater for second harmonic than for fundamental imaging (25.5 vs 7.1; P < 0.012). The mean contrast intensity qualitative score with harmonic imaging was higher (2.6 ± 0.73 vs 1.2 ± 0.44; P < 0.01) and the duration of contrast effect was longer (242 ± 131 s vs 53 ± 33 s; P < 0.004). Second harmonic imaging significantly enhanced contrast intensity and prolonged visible duration of contrast effect after a peripheral venous injection of Levovist.     

多普勒能量组织成像定量梗死心肌内膜面积的价值

目的：探讨多普勒能量组织成像技术（ＤＰＴＩ）定量梗死心肌内膜面积的价值。方法：用ＤＰＴＩ测量７条犬心肌梗死模型的梗死心肌内膜面积，并同病理染色结果对照。结果：ＤＰＴＩ和病理染色显示的梗死心肌内膜面积高度相关（ｒ＝０．７８，Ｐ＜０．０１）。结论：ＤＰＴＩ可作为定量梗死分析心肌内膜面积的有效方法。     

Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography

BACKGROUND: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall-motion analysis. Interpretation of dobutamine stress echocardiography is observer-dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. METHODS AND RESULTS: Twenty-nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5-3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. CONCLUSION: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.     

Pulsed Tissue Doppler Imaging to Assess Myocardial Viability by Quantification of Regional Myocardial Functional Reserve

Dobutamine stress echocardiography (DSE) is used widely to evaluate myocardial viability, but is limited by the subjective nature of test interpretation. Assessment of systolic function by pulsed tissue Doppler imaging (TDI) during dobutamine stimulation may allow a more objective evaluation of myocardial functional reserve and, thus, myocardial viability. In 30 patients (58 +/- 9 years) with prior myocardial infarction, pulsed TDI with low dose dobutamine stress (10 microg/kg/min) was performed to assess myocardial viability. Qualitative assessment of two-dimensional (2-D) DSE and positron emission tomography (PET) were used for comparison. Peak systolic myocardial velocity was measured for each left ventricular segment (16 segments) at baseline and low dose dobutamine stress using pulsed TDI. The absolute and relative increases of peak systolic velocity from rest to low dose dobutamine stress were calculated. Three hundred sixty-four segments with adequate pulsed TDI tracing were divided according to either 2-D DSE or PET findings into normal, viable (mismatch), and nonviable (match) segments. The increase of peak systolic myocardial velocity from baseline to low dose dobutamine was significantly different between segments defined as normal, viable, and nonviable by 2-D DSE (2.71 +/- 1.91 cm/sec, 1.86 +/- 2.15 cm/sec, and 0.99 +/- 1.16 cm/sec, respectively; P < 0.001). The increase of peak systolic myocardial velocity from rest to low dose dobutamine for normal, mismatch, and match segments defined by PET was 2.72 +/- 1.96, 1.01 +/- 0.96 and 0.80 +/- 1.07 cm/sec, respectively (P < 0.001). In conclusion, the increase of peak systolic myocardial velocity during low dose dobutamine stimulation determined by pulsed TDI distinguishes between different myocardial viability states. It complements the standard interpretation of stress echocardiograms.     

Blood Flow Assessment by Ultrasound‐Induced Destruction of Echocontrast Agents Using Harmonic Power Doppler Imaging: Which Parameters Determine Contrast Replenishment Curves?

OBJECTIVE: To evaluate the feasibility of flow determinations by contrast replenishment using harmonic power Doppler imaging (H-PDI). BACKGROUND: The application of indicator dilution principles on contrast echocardiography is limited by numerous methodical problems. Recently, a new method was introduced that relies on ultrasound-mediated microbubble destruction and evaluation of the contrast replenishment. METHODS: Definity, a perfluorocarbon-derived contrast agent under development, was continuously infused into a steady flow phantom and H-PDI registrations were performed within a silicone tube (d = 8 mm). Replenishment interval between destruction and imaging frame was varied from 0.04-2 seconds. Nonlinear curve fitting was performed using an exponential mathematical model. RESULTS: Strong linear correlation between contrast dose and maximum signal intensity as well as between flow and the slope variable beta of the replenishment curve was found for all settings (r > 0.96). Maximum signal intensity and contrast replenishment rate were found to be a function of emission power and were significantly influenced by depth and focus position. CONCLUSION: The feasibility of flow assessment using replenishment curves obtained by H-PDI was demonstrated. However, in experimental conditions, flow analysis was severely influenced by ultrasound system settings and imaging conditions such as emission power, sound field geometry, and investigation depth. For a clinical use of this promising approach, algorithms that take specific system settings and imaging conditions into account have to be found. Imaging modalities that enable a most homogeneous scan field are best suited for the assessment of contrast replenishment.     

Power Doppler Imaging as a Basis for Automated Endocardial Border Detection During Left Ventricular Contrast Enhancement

Echocardiographic evaluation of left ventricular (LV) systolic function relies on endocardial visualization, which can be improved when necessary using contrast enhancement. However, there is no method to automatically detect the endocardial boundary from contrast-enhanced images. We hypothesized that this could be achieved using harmonic power Doppler imaging. Twenty-two patients were studied in two protocols: (1) 11 patients with poorly visualized endocardium (> 3 contiguous segments not visualized) and (2) 11 consecutive patients referred for dobutamine stress echocardiography who were studied at rest and at peak dobutamine infusion. Patients were imaged in the apical four-chamber view using harmonic power Doppler mode (HP SONOS 5500) during LV contrast enhancement (Optison or Definity DMP115). Digital images were analyzed using custom software designed to automatically extract the endocardial boundary from power Doppler color overlays. LV cavity area was automatically measured frame-by-frame throughout the cardiac cycle, and fractional area change calculated and compared with those obtained by manually tracing the endocardial boundary in end-systolic and end-diastolic gray scale images. Successful border detection and tracking throughout the cardiac cycle was possible in 9 of 11 patients with poor endocardial definition and in 10 of 11 unselected patients undergoing dobutamine stress testing. Fractional area change obtained from power Doppler images correlated well with manually traced area changes (  r = 0.82 and r = 0.97  , in protocols 1 and 2, respectively). Harmonic power Doppler imaging with contrast may provide a simple method for semi-automated border detection and thus facilitate the objective evaluation of LV function both at rest and under conditions of stress testing. This methodology may prove to be particularly useful in patients with poorly visualized endocardium.