Pulse Inversion Doppler Research Articles

Detection of Individual Microbubbles by Burst-Wave-Aided Contrast-Enhanced Active Doppler Ultrasonography.

We propose burst-wave-aided, contrast-enhanced, active Doppler ultrasonography for visualizing lymph vessels. This technique forces ultrasound contrast agents (UCAs) to move using the acoustic radiation force induced by burst waves with low amplitude while suppressing their destruction. Using a flow phantom, we measured the average, decrease rate of echo intensity [i.e., pulse intensity integral (PII)], and the velocity of individual contrast agents, which directly affects the performance of imaging and tracking contrast agents under stationary flow conditions. Comparison with pulse-inversion Doppler without exposure to the burst wave demonstrated that the velocity of the contrast agents could be enhanced up to several tens of millimeters per second by the effect of the burst wave, maximizing the echo intensity extracted by a clutter filter. The contrast ratio (CR), defined as the ratio of the contrast echo to the phantom echo outside the channel, did not change appreciably, even when the lower cut-off velocity of the clutter filter was increased up to 10 mm/s. This implies a better robustness against the motion of the tissue. In addition, the performance for detecting contrast agents (i.e., echo intensity) was superior or similar to that of pulse-inversion Doppler, even in undesirable conditions where the flow had a velocity component in the opposite direction to that of the acoustic radiation force. The echo intensity was lower or the same as that in pulse-inversion Doppler, demonstrating the potential for suppressing the destruction of contrast agents and enabling long-term observations. From these results, we expect that the proposed method will be beneficial for visualizing lymph vessels.

Pseudo-Doppler effect at a disappearance of a single microbubble translating owing to acoustic radiation force

We attempted to visualize a single microbubble driven by acoustic radiation force using a combination of pulse inversion Doppler and plane wave imaging. Commercial microbubbles, Sonazoid® underwent ultrasound exposure with a center frequency of 5.2 MHz, a pulse repetition frequency of 4 kHz, and a negative peak sound pressure of 1.59 MPa. It succeeded in separately detecting individual microbubbles with high sensitivity. The disappearance of freely-translating microbubbles could be observed as a broadened spectrum of Doppler signal, i.e. a pseudo-Doppler effect. However, the trend was not apparent in the case of wall-colliding microbubbles.

Visualizing the Tumor Microvasculature With a Nonlinear Plane-Wave Doppler Imaging Scheme Based on Amplitude Modulation

Imaging with ultrasonic plane waves enables the combination of Doppler and microbubble contrast-enhanced imaging without compromising the Doppler ensemble length, as is the case for conventional line-by-line imaging, thus maintaining flow sensitivity. This permits the separation of conduit flow in large vessels from the perfusion background and the presentation of velocity estimates in real-time. However, the ability to differentiate perfusion from the tissue signal is limited by the contrast-to-tissue (CTR) ratio achieved with the contrast-enhanced pulsing sequence, independently of the acquisition length. One way to improve the CTR is to use a Doppler sequence based on amplitude modulation instead of one based on pulse inversion. In this work, we discuss how amplitude modulation can be adapted to Doppler processing. We show that amplitude modulation Doppler, like pulse inversion Doppler, can separate the signal of moving tissue from that of moving microbubbles, while achieving a better contrast-to-tissue ratio than pulse inversion Doppler, both in vitro and in vivo. Both amplitude modulation Doppler and pulse inversion Doppler yield similar velocity estimates when the bandwidth of the RF echo is properly compensated. Finally, we demonstrate how amplitude modulation Doppler can be used to reveal both the conduit flow and the capillary perfusion at high frame rates in an in vivo tumor.

Combined perfusion and doppler imaging using plane-wave nonlinear detection and microbubble contrast agents.

Plane-wave imaging offers image acquisition rates at the pulse repetition frequency, effectively increasing the imaging frame rates by up to two orders of magnitude over conventional line-by-line imaging. This form of acquisition can be used to achieve very long ensemble lengths in nonlinear modes such as pulse inversion Doppler, which enables new imaging trade-offs that were previously unattainable. We first demonstrate in this paper that the coherence of microbubble signals under repeated exposure to acoustic pulses of low mechanical index can be as high as 204 ± 5 pulses, which is long enough to allow an accurate power Doppler measurement. We then show that external factors, such as tissue acceleration, restrict the detection of perfusion at the capillary level with linear Doppler, even if long Doppler ensembles are considered. Hence, perfusion at the capillary level can only be detected with ultrasound through combined microbubbles and Doppler imaging. Finally, plane-wave contrast-enhanced power and color Doppler are performed on a rabbit kidney in vivo as a proof of principle. We establish that long pulse-inversion Doppler sequences and conventional wall-filters can create an image that simultaneously resolves both the vascular morphology of veins and arteries, and perfusion at the capillary level with frame rates above 100 Hz.

A new active cavitation mapping technique for pulsed HIFU applications-bubble doppler

In this work, a new active cavitation mapping technique for pulsed high-intensity focused ultrasound (pHIFU) applications termed bubble Doppler is proposed and its feasibility is tested in tissue-mimicking gel phantoms. pHIFU therapy uses short pulses, delivered at low pulse repetition frequency, to cause transient bubble activity that has been shown to enhance drug and gene delivery to tissues. The current gold standard for detecting and monitoring cavitation activity during pHIFU treatments is passive cavitation detection (PCD), which provides minimal information on the spatial distribution of the bubbles. B-mode imaging can detect hyperecho formation, but has very limited sensitivity, especially to small, transient microbubbles. The bubble Doppler method proposed here is based on a fusion of the adaptations of three Doppler techniques that had been previously developed for imaging of ultrasound contrast agents-color Doppler, pulse-inversion Doppler, and decorrelation Doppler. Doppler ensemble pulses were interleaved with therapeutic pHIFU pulses using three different pulse sequences and standard Doppler processing was applied to the received echoes. The information yielded by each of the techniques on the distribution and characteristics of pHIFU-induced cavitation bubbles was evaluated separately, and found to be complementary. The unified approach-bubble Doppler-was then proposed to both spatially map the presence of transient bubbles and to estimate their sizes and the degree of nonlinearity.

Myocardial Contrast Echocardiography for the Detection of Coronary Artery Disease in Patients with Global Hypokinesis Admitted for First-Onset Acute Heart Failure: Pilot Study

BackgroundThe non-invasive differentiation of ischemic and nonischemic acute heart failure (AHF) not resulting from acute myocardial infarction is difficult and has therapeutic and prognostic implications. The aim of this study was to assess whether resting myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD) in patients with decreased left ventricular (LV) systolic function and global hypokinesis presenting with AHF.MethodsTwenty-one consecutive patients underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during contrast IV infusion of Definity®. Following transient microbubbles destruction, the contrast replenishment rate (β), reflecting myocardial blood flow velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function: y (t) = A (1 - e-β(t-t0)) + C.ResultsOf the 21 (mean age 56.6 ± 13.6 years) patients, 5 (23.8%) demonstrated flow-limiting CAD (> 70% of luminal diameter narrowing). The mean ± standard deviation of LV ejection fraction was 29.6 ± 8.6%. Quantitative MCE analysis was feasible in 258 of 378 segments (68.3%). There were no significant difference in "β" and "Aβ" in patients without and with CAD (0.48 ± 0.27 vs. 0.45 ± 0.25, p = 0.453 for β and 2.99 ± 2.23 vs. 3.68 ± 3.13, p = 0.059 for Aβ, respectively). No contrast-related side effects were reported.ConclusionResting quantitative MCE analysis in patients with AHF was feasible, however, the parameters did not aid in detecting of CAD.

Comparison of pulse subtraction doppler and pulse inversion doppler

In this paper, a new Doppler technique based on pulse subtraction imaging (PSD) is described and compared with pulse inversion Doppler (PID). Combining a nonlinear contrast agent imaging technique with a Doppler process provides a tool for detecting motion of both contrast agents and tissues. This has potential in targeted imaging in which attached microbubbles need to be separated from moving ones and surrounding tissues. The results from both simulation and experiment show that PSD is able to differentiate bubble motion from tissue motion. For Doppler processing conducted at the fundamental frequency, the contrast-to-tissue ratio (CTR) in PSD was 3.3 (±0.4) times higher on average than PID at a mechanical index (MI) of 0.1. At the harmonic frequency, PID was shown to have a 3.1 (±0.4) times higher CTR than PSD. Overall, taken in their optimum processing conditions, PID has a CTR up to 1.9 (±0.4) times higher than PSD. The CTRs for both techniques have also been shown to increase with increasing MI. However, for the same axial Doppler resolution. PSD also allows less energy to be transmitted into the medium, which makes it less disruptive. The relative performances of PSD and PID in terms of the bandwidth of the imaging system are also discussed.

Pulse subtraction Doppler

Recent advances have demonstrated the feasibility of molecular imaging using targeted microbubbles and ultrasound. One technical challenge is to selectively detect attached bubbles from those freely flowing bubbles and surrounding tissue. Pulse Inversion Doppler is an imaging technique enabling the selective detection of both static and moving ultrasound contrast agents: linear scatterers generate a single band Doppler spectrum, while non-linear scatterers generate a double band spectrum, one being uniquely correlated with the presence of contrast agents and non-linear tissue signals. We demonstrate that similar spectrums, and thus the same discrimination, can be obtained through a Doppler implementation of Pulse Subtraction. This is achieved by reconstructing a virtual echo using the echo generated from a short pulse transmission. Moreover by subtracting from this virtual echo the one generated from a longer pulse transmission, it is possible to fully suppress the echo from linear scatterers, while for non-linear scatterers, a signal will remain, allowing classical agent detection. Simulations of a single moving microbubble and a moving linear scatterer subject to these pulses show that when the virtual echo and the long pulse echo are used to perform pulsed Doppler, the power Doppler spectrum allows separation of linear and non-linear moving scattering. Similar results are obtained on experimental data acquired on a flow containing either microbubble contrast agents or linear blood mimicking fluid. This new Doppler method constitutes an alternative to Pulse Inversion Doppler and preliminary results suggest that similar dual band spectrums could be obtained by the combination of any non-linear detection technique with Doppler demodulation.

Quantification of resting myocardial blood flow velocity in normal humans using real-time contrast echocardiography. A feasibility study

BackgroundReal-time myocardial contrast echocardiography (MCE) is a novel method for assessing myocardial perfusion. The aim of this study was to evaluate the feasibility of a very low-power real-time MCE for quantification of regional resting myocardial blood flow (MBF) velocity in normal human myocardium.MethodsTwenty study subjects with normal left ventricular (LV) wall motion and normal coronary arteries, underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during constant IV. infusion of SonoVue®. Following transient microbubble destruction, the contrast replenishment rate (β), reflecting MBF velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function; y (t) =A (1-e-β(t-t0)) + C.ResultsQuantification was feasible in 82%, 49% and 63% of four-chamber, two-chamber and apical long-axis view segments, respectively. The LAD (left anterior descending artery) and RCA (right coronary artery) territories could potentially be evaluated in most, but contrast detection in the LCx (left circumflex artery) bed was poor. Depending on localisation and which frames to be analysed, mean values of were 0.21–0.69 s-1, with higher values in medial than lateral, and in basal compared to apical regions of scan plane (p = 0.03 and p < 0.01). Higher β-values were obtained from end-diastole than end-systole (p < 0.001), values from all-frames analysis lying between.ConclusionLow-power real-time MCE did have the potential to give contrast enhancement for quantification of resting regional MBF velocity. However, the technique is difficult and subjected to several limitations. Significant variability in β suggests that this parameter is best suited for with-in patient changes, comparing values of stress studies to baseline.

Differences in definity and optison microbubble destruction rates at a similar mechanical index with different real-time perfusion systems

The purpose of this study was to determine microbubble responses to different pulse sequence schemes that exist on low mechanical index (MI) real-time perfusion imaging systems using either intravenous albumin-coated (Optison) or lipid-encapsulated (Definity) microbubbles. A tissue-mimicking phantom was created that permitted insonation of microbubbles at 3 cm (near field) and 9 cm (far field) from the diagnostic transducer face. Differences in effluent microbubble concentration were measured after they passed through vessels being insonified with pulse sequence schemes that transmitted alternating polarity (pulse inversion Doppler), alternating amplitude (power modulation), or both (contrast pulse sequencing) at a similar MI, frame rate, and transmit frequency. Normalized contrast signal intensity within a recirculating chamber was also measured in the near and far field. Pulse inversion Doppler produced less initial normalized contrast signal intensity and greater destruction rates than amplitude varying pulse sequence schemes like power modulation or contrast pulse sequencing at both the 0.1- and 0.2-MI settings. These differences indicate that the same MI setting on different real-time perfusion imaging techniques will produce different microbubble responses.

Microbubble responses to a similar mechanical index with different real-time perfusion imaging techniques.

The purpose of this study was to determine differences in contrast enhancement and microbubble destruction rates with current commercially available low-mechanical index (MI) real-time perfusion imaging modalities. A tissue-mimicking phantom was developed that had vessels at 3 cm (near field) and 9 cm (far field) from a real-time transducer. Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) were injected proximal to a mixing chamber, and then passed through these vessels while the region was insonified with either pulses of alternating polarity with pulse inversion Doppler (PID) or pulses of alternating amplitude by power modulation (PM) at MIs of 0.1, 0.2 and 0.3. Effluent microbubble concentration, contrast intensity and the slope of digital contrast intensity vs. time were measured. Our results demonstrated that microbubble destruction already occurs with PID at an MI of 0.1. Contrast intensity seen with PID was less than with PM. Therefore, differences in contrast enhancement and microbubble destruction rates occur at a similar MI setting when using different real-time pulse sequence schemes.

Myocardial Contrast Echocardiography Yields Best Accuracy Using Quantitative Analysis of Digital Data from Pulse Inversion Technique: Comparison with Second Harmonic Imaging and Harmonic Power Doppler During Simultaneous Dipyridamole Stress SPECT Studies

This prospective study assesses the (1) feasibility of quantifying ultrasound myocardial perfusion studies based on the densitometric analysis of digital data and the (2) comparison of pulse inversion, second harmonic and harmonic power Doppler modalities with SPECT. Twenty-three patients with suspected ischaemic heart disease had i.v. injections of Tc-Sestamibi and Optison during a dipyridamole stress test for echocardiography in pulse inversion, second harmonic and harmonic power Doppler mode. Analysis was (a) visual by scoring and (b) quantitative by densitometry of digital data for background subtracted myocardial opacification (a.u.) and normalized contrast effect (%). In the nine control patients, myocardial opacification at stress was greater (P< or =0.002) than in the pathologic group (5. +/- 3.3 vs 2.6 +/- 2.5 a.u. in pulse inversion, 5.4 +/- 2.1 vs 2.4 +/- 1.8 in second harmonic and 7.1 +/- 3.7 vs 4.9 +/- 3.7 a.u. in harmonic power Doppler). In the pathologic group, normalized contrast effect decreased significantly during stress (23.7 +/- 18.8 to 11.3 +/- 10.8%, P<0.003) only in pulse inversion. Kappa values for patient based diagnostic agreement with SPECT were 0.75 by pulse inversion, 0.62 by second harmonic and 0.52 by harmonic power Doppler for quantitative analysis, and 0.51, 0.37 and 0.35 respectively, for visual assessment. Myocardial contrast echocardiography should be analysed using densitometry of digital data. The new technique pulse inversion demonstrates best agreement with SPECT data.

Myocardial Contrast Echocardiography Yields Best Accuracy Using Quantitative Analysis of Digital Data from Pulse Inversion Technique: Comparison with Second Harmonic Imaging and Harmonic Power Doppler During Simultaneous Dipyridamole Stress SPECT Studies

Aims: This prospective study assesses the (1) feasibility of quantifying ultrasound myocardial perfusion studies based on the densitometric analysis of digital data and the (2) comparison of pulse inversion, second harmonic and harmonic power Doppler modalities with SPECT. Methods and Results: Twenty-three patients with suspected ischaemic heart disease had i.v. injections of Tc-Sestamibi and Optison ® during a dipyridamole stress test for echocardiography in pulse inversion, second harmonic and harmonic power Doppler mode. Analysis was (a) visual by scoring and (b) quantitative by densitometry of digital data for background subtracted myocardial opacification (a.u.) and normalized contrast effect (%). In the nine control patients, myocardial opacification at stress was greater ( P ≤0·002) than in the pathologic group (5·8±3·3 vs 2·6±2·5 a.u. in pulse inversion, 5·4±2·1 vs 2·4±1·8 in second harmonic and 7·1±3·7 vs 4·9±3·7 a.u. in harmonic power Doppler). In the pathologic group, normalized contrast effect decreased significantly during stress (23·7±18·8 to 11·3±10·8%, P <0·003) only in pulse inversion. Kappa values for patient based diagnostic agreement with SPECT were 0·75 by pulse inversion, 0·62 by second harmonic and 0·52 by harmonic power Doppler for quantitative analysis, and 0·51, 0·37 and 0·35 respectively, for visual assessment. Conclusion: Myocardial contrast echocardiography should be analysed using densitometry of digital data. The new technique pulse inversion demonstrates best agreement with SPECT data. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved .

Instrumentation for contrast echocardiography.

A number of new imaging methods have been developed specifically for use with ultrasound contrast agents. These methods rely on the peculiar behavior of microbubbles in an ultrasound field. At low incident acoustic pressures (reflected by the mechanical index, MI) microbubbles emit harmonics. These can be detected using harmonic or pulse inversion imaging. At higher MI, bubbles are disrupted, emitting a strong, nonlinear echo. Harmonic power Doppler methods are able to detect this echo, offering the most sensitive method for the detection of microbubble at the perfusion level. Although the first images of myocardial perfusion were made using this disruption method, it requires intermittent imaging with interframe intervals of up to 6 heart beats. Pulse inversion Doppler imaging is a newer method that is able to detect the nonlinear component of bubble echoes at a very low MI, thereby making possible real-time myocardial perfusion imaging. An understanding of the behavior of bubbles during an imaging examination is an essential prerequisite to its success in clinical practice.

Real-time perfusion imaging with low mechanical index pulse inversion Doppler imaging

OBJECTIVESWe sought to determine how successful pulse inversion Doppler (PID) imaging would be in detecting myocardial perfusion defects during dobutamine stress echocardiography.BACKGROUNDBy transmitting multiple pulses of alternating polarity (PID) at a low mechanical index, myocardial contrast enhancement from intravenously injected microbubbles can be detected using real-time frame rates.METHODSPulse inversion Doppler imaging was performed in 117 patients during dobutamine stress echocardiography by using an intravenous bolus of a perfluorocarbon-filled, albumin- (Optison: n = 98) or liposome- (Definity: n = 19) encapsulated microbubble and a mechanical index of <0.3. The visual identification of myocardial contrast defects and wall motion abnormalities was determined by blinded review. Forty of the patients had quantitative angiography (QA) performed to correlate territorial contrast defects with stenosis diameter >50%.RESULTSThere was a virtual absence of signal from the myocardium before contrast injections in all patients. Bright myocardial opacification at peak stress was observed in at least one coronary artery territory at frame rates up to 25 Hz in 114 of the 117 patients during dobutamine stress echocardiography. Regional myocardial contrast defects at peak stress were observed in all 30 patients with >50% stenosis in at least one vessel (13 with single-vessel and 17 with multivessel disease). Contrast defects were observed in 17 territories subtended by >50% diameter stenosis that had normal wall motion at peak stress. Overall agreement between QA and myocardial contrast enhancement on a territorial basis was 83%, as compared with 72% for wall motion.CONCLUSIONSPulse inversion Doppler imaging allows the detection of myocardial perfusion abnormalities in real-time during stress echocardiography and will further add to the quality and sensitivity of this test.

Future directions in ultrasound contrast agent research

Since the introduction of Levovist® in Europe and Albunex® in the United States, interest in ultrasound contrast agents has increased enormously. This change is reflected in the ensuing rapid pace of technical development, and the depth of the discussions during this topical meeting. Before Albunex®, it was essentially impossible to convince an equipment manufacturer to devote time to the development of contrast-specific imaging modalities. After Albunex®, harmonic gray-scale imaging was in the clinic within the year, followed by harmonic color Doppler imaging, power Doppler, pulse inversion gray scale, pulse inversion Doppler, power modulation, coherent contrast imaging, and so on. The trend continues today as old techniques are improved, new techniques (e.g., subharmonic imaging) are tested and new approaches (e.g., phase-shift imaging) are conceived. Similarly, rapid advances have occurred in other areas, with models now including the details of shell viscoelasticity, in vitro studies now imaging single bubble dynamics to microsecond resolution, and specially designed microbubbles being used for targeted imaging, drug delivery, and gene therapy. Even bioeffects research has ‘‘advanced’’ with the discovery of imaging-modality-dependent contrast agent effects such as induction of premature ventricular contractions. Selected aspects of each of these areas will be discussed.

Nonlinear imaging

Nonlinear imaging

Detection procedures of ultrasound contrast agents

In the early days, it was believed that ultrasound contrast agents (UCA) could be sufficiently detected and imaged with the conventional imaging methods nowadays referred to as fundamental imaging. Newer imaging techniques proved to be more sensitive and are based on specific properties of the UCA. In general, these new characteristics involve non-linear and transient characteristics of contrast agents that appear at the high end of the diagnostic acoustic intensity. Imaging modalities used today for UCA are, besides fundamental imaging, second harmonic imaging, power Doppler, harmonic power Doppler, pulse inversion and pulse inversion Doppler, multi-pulse imaging and subharmonic imaging. Although the results of conventional second harmonic imaging are still not optimal for perfusion imaging applications, in combination with Doppler techniques (colour Doppler, power Doppler) it is one of the most sensitive techniques currently available in terms of agent-to-tissue ratio. Further improvements in current and future detection methods demand a complete understanding of the ultrasound–UCA interaction.

Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents

A novel technique for the selective detection of ultrasound contrast agents, called pulse inversion Doppler, has been developed. In this technique, a conventional Doppler or color Doppler pulse sequence is modified by inverting every second transmit pulse. Either conventional or harmonic Doppler processing is then performed on the received echoes. In the resulting Doppler spectra, Doppler shifts from linear and nonlinear scattering are separated into two distinct regions that can be analyzed separately or combined to estimate the ratio of nonlinear to linear scattering from a region of tissue. The maximum Doppler shift that can be detected is 1/2 the normal Nyquist limit. This has the advantage over conventional harmonic Doppler that it can function over the entire bandwidth of the echo signal, thus achieving superior spatial resolution in the Doppler image. In vitro measurements comparing flowing agent and cellulose particles suggest that pulse inversion Doppler can provide 3 to 10 dB more agent to tissue contrast than harmonic imaging with similar pulses. Similar measurements suggest that broadband pulse inversion Doppler can provide up to 16 dB more contrast than broadband conventional Doppler. Nonlinear propagation effects limit the maximum contrast obtainable with both harmonic and pulse inversion Doppler techniques.

New ultrasound contrast agents for left ventricular and myocardial opacification.

Until recently, the use of contrast agents with 2-dimensional echocardiography has been limited to the detection of intracardiac shunts or abnormal venous connections. The advent of commercially available transpulmonary contrast agents and progress in imaging technology changed this situation. New indications for contrast echocardiography include improved assessment of ventricular function by endocardial border enhancement and the assessment of myocardial perfusion. The major advantage of novel contrast agents is their persistence in circulation, due to the content of a gas that is poorly soluble in plasma or a specific microcapsule wall composition. These features, in conjunction with advanced imaging techniques (intermittent harmonic imaging, harmonic power Doppler, pulse inversion Doppler) allow the detection of minute amounts of the agents in myocardium. There are more than 10 echocardiographic contrast agents undergoing clinical or late preclinical tests. Apart from commercially available Albunex, Levovist, Optison, such agents as EchoGen, Quantison, NC100100 and PESDA have been successfully used in humans. Initial clinical data demonstrating the feasibility of myocardial perfusion studies in patients have been presented for PESDA, Optison, Quantison and NC100100. Early attempts are being made for therapeutic applications of microbubbles, including ultrasound-intensified thrombolysis, tissue targeting and drug delivery. Rapid progress in microbubble technology and imaging techniques has raised a wide interest of the clinicians for contrast echocardiography, which may soon become an established technique for the evaluation of myocardial perfusion, competitive for radionuclide imaging.