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PubMed2005

[Contrast echocardiography: from diagnosis to treatment].

Contrast echocardiography is widely used in echocardiographic laboratories. When used at rest or with a stress test, it provides complementary information concerning myocardial perfusion not available with conventional imaging. Its applications in the evaluation of left ventricular ejection fraction, the detection of coronary stenosis and the no reflow phenomenon in acute myocardial infarction have been validated. Advances in our understanding of the interaction between the microbubbles and ultrasound have led to considering the microbubble not just as a vascular tracer but also as a vector of active molecules. The detection of angiogenesis, thrombi, or intravascular inflammation are possible with contrast echocardiography. Therefore, new perspectives in myocardial contrast echo are opening up in therapeutics. Preliminary studies in the animal suggest that it may be possible to use microbubbles to deliver drugs or genetic material to the heart of the cardiomyocytes.

Animals↗

PubMed2005

Transient subharmonic and ultraharmonic acoustic emission during dissolution of free gas bubbles.

This work concerns the study of free gas bubble behavior, a basic step in contrast agent study. In order to improve the understanding of microbubble-ultrasound interaction, we propose an acoustic dynamic observation of microbubble behavior performed by a high frame-rate acquiring and processing system. Results from ultrasonic observations of free gas microbubbles are discussed and compared with theoretical simulation. Peculiar radio frequency (RF) echo signals back-propagated from bubbles during dissolution up to their destruction are shown and their behavior is discussed. In particular, the different orders of subharmonic emissions related to changes in bubble sizes during dissolution were observed.

Acoustics↗

PubMed2006

Vascular distribution of an ultrasound contrast agent used to simulate decompression bubbles.

OBJECTIVE: The objectives of this preliminary work were to evaluate the distribution of an ultrasound contrast agent (UCA) (microbubbles) in different arterial regions (brain, kidney, lower limbs) using the Doppler spectrum brightness analysis and to discuss the results in the context of decompression physiology. METHOD: There were four patients who instrumented with two pulsed Doppler sensors in order to monitor in real-time the spectrum of the middle cerebral femoral arteries. Renal arteries were investigated using an echo-Doppler probe handled by a sonographer. Measurements of the systolic mean, diastolic frequencies, qualitative, and quantitative analysis of the spectrum brightness intensity were performed before and after intravenous injection of a UCA. RESULTS: All of the systolic mean and diastolic arterial frequencies remained constant during the experiment. Some seconds after the first injection, the cerebral spectrum was heterogeneously enhanced with strong flashes over the entire spectrum. The renal and femoral spectrums were homogeneously reinforced. The spectrum brightness patterns did not change during the first 10 min. DISCUSSION: This work shows that the distribution of the UCA microbubbles within the vessel sections changed according to the distance from the heart, as suggested by the spectrum recorded at different sites. By mixing the blood, the heart could re-aggregate the UCA particles, even when they returned from the distal vascular regions where they were homogeneously distributed. The circulating microbubbles and their distribution within the arteries should be considered in decompression procedures with repetitive dives.

Adult↗

PubMed2002

The value of contrast-enhanced color Doppler ultrasound in the detection of vascularization of finger joints in patients with rheumatoid arthritis.

OBJECTIVE: A prospective study was performed to assess the usefulness of contrast-enhanced color Doppler ultrasound (CDUS) in the evaluation of intraarticular vascularization of finger joints in patients with rheumatoid arthritis (RA). METHODS: We investigated 198 finger joints in 46 patients with RA, and 80 finger joints in 10 healthy volunteers. Joints with varying levels of clinical activity of inflammation were classified as being active, moderately active, or inactive. CDUS was performed with a high-frequency multi-D linear array transducer. A microbubble-based ultrasound (US) contrast agent (Levovist; Schering, Berlin, Germany) was intravenously infused. Doppler findings were rated on the basis of both unenhanced and contrast-enhanced CDUS images. RESULTS: Healthy joints showed no intraarticular vascularization on either unenhanced or contrast-enhanced CDUS. Unenhanced CDUS detected intraarticular vascularization in 7 (8%) of 83 inactive joints, in 31 (52%) of 60 moderately active joints, and in 32 (58%) of 55 active joints. Contrast-enhanced CDUS detected intraarticular vascularization in 41 (49%) of 83 joints with inactive RA, in 59 (98%) of 60 joints with moderately active RA, and in all 55 joints with active RA. Detection of intraarticular vascularization was improved by administration of the microbubble-based US contrast agent (P < 0.001). Contrast-enhanced CDUS demonstrated differences in intraarticular vascularization between joints with inactive RA and those with active RA (P < 0.001), between joints with inactive RA and those with moderately active RA (P < 0.001), and between joints with moderately active RA and those with active RA (P < 0.001). CONCLUSION: The use of a microbubble-based US contrast agent significantly improved the detection of intraarticular vascularization in the finger joints of patients with RA. This technique seems to be a useful adjunct in the assessment of disease activity.

Adult↗

PubMed1992

Portal vein reflectors: duplex sonographic appearance.

Duplex sonography has established utility in the noninvasive evaluation of the portal venous system. Recently, the duplex sonographic features of suspected portal venous air have been described. We report on an experimental study in dogs undertaken to establish if the same sonographic features could be reproduced in a laboratory setting and to determine if small fragments of clot emboli could produce similar gray-scale and Doppler findings. Injections of microbubbles of air and clot fragments into the portal venous system were monitored using duplex ultrasound. The gray-scale and Doppler features of flow in the main portal vein were indistinguishable in both microbubble and clot injections. Superimposition of high-amplitude spikes on the normal portal venous waveform was seen in 19 of 24 (79%) microbubble and 13 of 23 (56%) clot fragment injections. We conclude that the appearance of rapidly moving, bright intraluminal echoes coupled with spike-like aberrations of the portal venous waveform can be associated with portal venous air bubbles or small blood clot emboli.

Animals↗

PubMed2002

Interaction of normal saline solution with ultrasound contrast medium: significant implication for sonographic diagnosis of vesicoureteral reflux.

The sonographic diagnosis of vesicoureteral reflux with intravesical administration of ultrasound contrast media is on the rise. In few cases did we encounter rapid dissolution of microbubbles in the bladder filled with normal saline. The aim of this study was to find out whether there is any interaction between normal saline and ultrasound contrast media and, if so, to elucidate the cause for the interaction. In an in vitro experimental setup the mixtures of various normal saline solutions and a galactose-based ultrasound contrast medium (Levovist) were scanned under pre-defined parameters. The duration of contrast was determined. Oxygen concentration of the solutions was measured (pO(2) and O(2) mg/l). The US contrast medium had significantly longer contrast duration when mixed with normal saline from plastic containers rather than glass containers. The contrast duration difference was even more between normal saline from containers sealed under vacuum and those not sealed under vacuum: 0.7 and 12 min, respectively. The oxygen concentration in normal saline from vacuum-sealed containers is one-third or less that from non-vacuum-sealed containers. The high concentration of dissolved oxygen in the normal saline seems to prevent the diffusion of air from the microbubbles into the solution and thus their collapse. Desaturated normal saline has detrimental effect on microbubbles of the galactose-based US contrast medium. For the purpose of filling the bladder during contrast-enhanced voiding urosonography only normal saline solution from non-vacuum-sealed containers should be used. For practical purposes, normal saline from plastic containers is safest.

Administration, Intravesical↗

PubMed2002

Intraperitoneal distribution of ultrasound contrast medium imaged with B-mode ultrasound and colour-stimulated acoustic emission imaging.

Intraperitoneal port catheter systems for local delivery of cytotoxic drugs require imaging prior to chemotherapy to confirm homogenous distribution of an injected fluid in the entire peritoneal cavity. This study was performed to assess whether contrast-enhanced ultrasound (US) is a suitable imaging modality for this task. Twelve patients with peritoneal carcinosis and an implanted intraperitoneal port catheter system were studied before chemotherapy. Ultrasound examinations were performed after bolus injections of the microbubble contrast medium Levovist. Distribution of the contrast medium in the peritoneal cavity was imaged using B-mode US and colour-stimulated acoustic emission imaging (SAE). Contrast-enhanced CT imaging was used as term of reference for evaluating the US results. Distribution of the microbubbles in the peritoneal cavity was easily detected by both US methods. In 10 of 12 patients a free distribution in all abdominal quadrants was seen with both US techniques. In 2 of 12 patients, CT and US showed contrast medium limited to the perihepatic area. Therapy was stopped and surgical repositioning of the catheter was performed. Ultrasound after intraperitoneal injection of a microbubble contrast agent provides reliable information about the distribution of intraperitoneally injected fluid in the peritoneal cavity. This method is therefore well suited for imaging port catheter systems prior to chemotherapy.

Acoustics↗

PubMed2005

Benign focal liver lesions: spectrum of findings on SonoVue-enhanced pulse-inversion ultrasonography.

The prevalence of benign focal liver lesions (BFLL) is high both in the general population and in patients with known malignancies. The gray-scale ultrasound (US) technique is usually the first-line imaging modality used in the radiological workup of such lesions, but unfortunately it lacks specificity. Furthermore, Doppler examination may often be unsatisfactory owing to motion artefacts, or when small or deeply located lesions are evaluated. Recently, microbubble-based contrast agents used in combination with gray-scale US techniques, which are very sensitive to nonlinear behavior of microbubbles, have led to a better depiction of both microvasculature and macrovasculature of focal hepatic masses, thus improving the reliability of using US in the assessment of liver tumors. This review illustrates the spectrum of enhancement patterns of BFLL on contrast-enhanced ultrasonography with SonoVue, a second-generation microbubble-based contrast agent.

Adenoma, Liver Cell↗

PubMed2001

Developments in ultrasound contrast media.

Ultrasound microbubble contrast agents are effective and safe echo enhancers. An ingenious array of methods are employed to achieve stability and provide a clinically useful enhancement period. Microbubbles enhance ultrasound signals by up to 25 dB (greater than 300-fold increase) due to resonant behaviour. This is used to rescue failed Doppler studies and may be extended to image the microcirculation of tumours and the myocardium using non-linear modes. Functional studies open up a whole range of applications by using a variety of active and passive quantitation techniques to derive indices from the transit of contrast through a tissue of interest. This has been especially successful in the detection of liver metastases and cirrhosis and shows great promise as a clinical tool. It also has great potential in measuring microcirculatory flow velocity. The demonstration that some microbubbles are not just pure blood pool agents but have a hepatosplenic specific phase has extended the versatility of ultrasound. Imaging of this stationary phase with non-linear modes such as phase inversion and stimulated acoustic emission, has improved the sensitivity and specificity of ultrasound in the detection and characterisation of focal liver lesions to rival that of CT and MR.

Contrast Media↗

PubMed2001

Tissue harmonic and contrast-specific imaging: back to gray scale in ultrasound.

The development of new US techniques that produce images based on nonlinear acoustic effects of US interaction with matter or microbubble contrast agents has opened new prospects for gray-scale US in native tissue and contrast imaging. Tissue harmonic imaging uses higher frequencies generated on propagation of the US beam through matter to improve image quality and resolve small anatomic structures and details, and is becoming a routine approach in US examination of many abdominal districts. Contrast-specific imaging techniques display enhancement of US agents in gray-scale with optimal contrast and spatial resolution, and offer high sensitivity either to microbubble movement or to microbubble destruction in dependence of the level of the applied acoustic peak pressure. Owing to the ability to exploit the microcirculation, contrast-specific techniques have enabled the evolution of contrast US from vascular imaging to the imaging of perfused tissues. Several studies have shown that these methods can substantially improve US detection and characterization of focal liver lesions, and promising results have been reported in other areas of investigation. This article reviews physical principles, technical issues, and clinical applications of tissue harmonic and contrast-specific imaging. It is foreseen that the new gray-scale US techniques will rapidly become a tool in numerous clinical scenarios.

Carcinoma, Hepatocellular↗

PubMed2005

Continuous monitoring of middle cerebral artery recanalization with transcranial color-coded sonography and Levovist.

BACKGROUND AND PURPOSE: Treatment of acute ischemic stroke with intravenous recombinant tissue plasminogen activator (rtPA) is relatively ineffective in patients with large vessel occlusion. Numerous experimental studies have demonstrated that ultrasound (US) can accelerate enzymatic fibrinolysis and acceleration of lysis by US is enhanced in the presence of microbubbles used as echo-contrast agents. The purpose of this study was to evaluate the feasibility of continuous monitoring of middle cerebral artery (MCA) recanalization using transcranial color-coded sonography (TCCS) and intravenously administered microbubbles. METHODS: Recanalization of middle cerebral artery (MCA) mainstem occlusion was assessed using continuous monitoring with TCCS and intravenously administered galactose-based microbubbles (Levovist) in 8 consecutive patients with acute ischemic stroke treated with intravenous rt-PA within 3 hours of symptom onset. RESULTS: Recanalization at one hour occurred in 4 of 8 patients. The median NIHSS score was 21 (range 10 to 28) at baseline, 15 (range 0 to 24) at 1 h, and 11 (range 0 to 22) at 24 h. Asymptomatic hemorrhagic transformation (HT) was demonstrated on brain imaging in 6 patients. CONCLUSION: This study demonstrates the feasibility of continuous monitoring of MCA recanalization using TCCS and Levovist, in acute stroke patients. The findings suggest a high rate of asymptomatic HT in monitored patients. Although all HTs were asymptomatic and did not preclude early clinical improvement, particular attention should be given to the incidence and clinical significance of HT in future studies using these methods.

Angioplasty, Balloon↗

PubMed1987

Successful left ventricular opacification following peripheral venous injection of sonicated contrast agent: an experimental evaluation.

A new agent for use in contrast echocardiography that is capable of passing through the pulmonary circulation and opacifying the left ventricular cavity after intravenous injection was evaluated in a canine model. Air-filled albumin microbubbles were produced by sonication. A Coulter counter was used to size and count the resultant microbubbles in vitro. The microbubbles had diameters sufficiently small (less than 9 micron) to permit transpulmonary passage. A total of 72 injections were made into the forepaw vein of five closed-chest dogs. Simultaneous two-dimensional echocardiographic images of the right ventricle and the left ventricle were recorded and digitized on an off-line computer. Of the 72 injections, 59 (82%) were suitable for digitization. Forty of the 59 digitized injections (68%) demonstrated left ventricular contrast enhancement. Indicator-dilution curves were generated from plots of intraventricular gray level VS time, and the curve widths and areas under the curves were determined. The ratio of total indicator curve area for left to right ventricular cavity was 0.39 for the 40 successful injections, indicating transpulmonary transmission of 39% of the contrast effect. Injection of bubbles with mean size less than 6 microns resulted in a larger median left ventricular curve area than those with bubbles averaging from 6 to 9 microns. Injections demonstrating successful left ventricular contrast opacification had larger right ventricular curve areas than those that were not successful. Blood pressure, heart rate, and arterial blood gases were not significantly altered by repeated intravascular contrast injections. Postmortem examination of hearts, lungs, livers, and kidneys revealed no histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Two-dimensional contrast echocardiography with carbon dioxide in the detection of congenital cardiac shunts.

Medically pure (100%) carbon dioxide directly injected into a peripheral vein was used for 2-dimensional contrast echocardiography in 134 patients with an arteriovenous shunt demonstrated by cardiac catheterization and cineangiography, Qp/Qs ratios of 1.5 to 3.7, pulmonary-to-systemic peak systolic pressure ratios of 0.2 to 0.8 and no oximetrically demonstrable venoarterial shunt. Two patients with transposition of the great arteries, intact ventricular septum and a Senning operation as well as 30 normal subjects of comparable age also were studied. In patients with an atrial septal defect, the gas microbubbles opacified the left atrium. In patients with a ventricular septal defect, the gas microbubbles opacified the left ventricle, whereas the left atrium was free of contrast. In all patients with patent ductus arteriosus, the gas microbubbles opacified the abdominal aorta, whereas the left atrium, left ventricle, aortic root and aortic arch remained free of contrast. In 2 patients in whom an aneurysm of the sinus of Valsalva ruptured into the right ventricle, the "negative" contrast effect permitted localization of the shunt. In 2 patients with transposition of the great arteries, an intact ventricular septum and a Senning operation, the intracardiac flow pattern was clearly demonstrated. No complication was observed. We conclude that pure carbon dioxide directly injected into a peripheral vein is a safe and advantageous echocardiographic contrast material. Because of its greater diffusibility in comparison with oxygen and fluid contrast media, small venoarterial shunting can be detected in defects such as atrial septal defect, ventricular septal defect and patent ductus arteriosus, in which only an arteriovenous shunt can be demonstrated by oximetry.

Adolescent↗

PubMed1989

Assessment of regional myocardial blood flow with myocardial contrast two-dimensional echocardiography.

It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo.

Animals↗

PubMed1990

Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation.

To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations.

Animals↗

PubMed1996

Patent foramen ovale: association between the degree of shunt by contrast transesophageal echocardiography and the risk of future ischemic neurologic events.

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt ( > or = 20 microbubbles) and group 2 (n = 18) with a "small" degree of shunt ( > or = 3 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p = 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patient foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk of subsequent adverse neurologic events compared with patients with a small degree of shunt.

Anticoagulants↗

PubMed2002

Detection of inflamed plaques with contrast ultrasound.

Inflammatory cell infiltration is an important factor in the progression and instability of atherosclerotic plaques. There has been great interest in the development of noninvasive methods that can assess these inflammatory processes to detect vulnerable plaques or patients, and to assess novel therapies. This review focuses on some recent advances in contrast-enhanced ultrasound (CEU), which can potentially be used for imaging plaque inflammation. These methods rely on ultrasound detection of microbubble contrast agents that are targeted to inflamed tissue. For this purpose, novel microbubbles have been formulated that are targeted either to activated leukocytes adherent to inflamed endothelium, or to endothelial cell adhesion molecules (p-selectin, intercellular adhesion molecule-1, alpha(v)beta(3)) expressed on the plaque surface or within plaque neovessels. Microbubble targeting has been achieved by modifications of shell components or conjugation of specific ligands to the shell surface. Although application of targeted CEU for imaging inflamed plaques is at the early stages of development, it is potentially easily translatable to routine clinical practice because the technique is relatively inexpensive, portable, and uses technology that already is used widely to evaluate vascular disease.

Animals↗

PubMed2003

Contrast echocardiography: potential for the in-vivo study of pediatric myocardial preservation.

BACKGROUND: Myocardial contrast echocardiography (MCE) has been used successfully during adult cardiac surgery to image myocardial perfusion. Recently it has been suggested this technique is capable of detecting microvascular injury and inflammation because sonicated albumin microbubbles adhere to activated neutrophils and, in the presence of denuded or inflamed endothelium, they persist within the microvasculature rather than passing unimpeded, which results in profound slowing of their transit rates. The technique has not previously been used during congenital heart surgery; however significant potential is suggested in this setting in which myocardial inflammation may contribute to postoperative myocardial dysfunction, a leading cause of morbidity and mortality. We have performed a preliminary study to assess the safety and feasibility of MCE in the pediatric intraoperative environment and to examine myocardial transit rates. METHODS: Sonicated albumin microbubbles were injected with cardioplegia during bypass in 16 children (aged 3 weeks to 8.5 years). Images were collected using transesophageal echocardiography. Complications, post-bypass electrocardiographic, echocardiographic, and outcome data were recorded. Myocardial transit rates were calculated using videointensity analysis, assessed for reproducibility and correlated with demographic and intraoperative variables and postoperative outcome. RESULTS: The technique was performed safely, with good reproducibility. Myocardial persistence of microbubbles, which occurred in 6 patients, was associated with crystalloid cardioplegia, prolonged preischemic bypass (r = 0.72, p = 0.004), or ischemic time (r = 0.69, p = 0.002). CONCLUSIONS: Intraoperative MCE shows potential as an in vivo technique for the study of pediatric myocardial preservation.

Albumins↗