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PubMed1985

Aerosol versus solution composition in occupational exposures.

Some industrial processes, such as the electrolysis of zinc solutions, anodic oxidation of aluminum, ore flotation, etc., result in the generation of gas microbubbles; the composition of their liquid envelope depends on, but is not identical to, the composition of the bulk of the liquid phase. An aerosol of respirable size, often toxic or irritant, results from the bursting of the bubbles at a certain height above the liquid. Some factors governing the discrepancy between the composition of the aerosol and that of the liquid have been studied for metal ions in oceanic aerosols. It is not known if these factors also apply to concentrated solutions and to anions.

Aerosols↗

PubMed1982

Contrast echocardiography.

Contrast echocardiography is the technique of injecting an echo-producing, biologically compatible solution into the bloodstream and using M-mode and/or two-dimensional echocardiography to observe intracardiac bloodflow patterns revealed by the resulting cloud of echoes. This information was previously available only from angiocardiography. Contrast echocardiography has become a well-established adjunct to M-mode and two-dimensional echocardiographic examination and is valuable in the identification and validation of normal and abnormal cardiac structures, for the demonstration (and exclusion) of intracardiac as well as extracardiac shunts, and in the diagnosis of valvular regurgitation. In addition many clinical applications are being developed. Future research directions include development of videodensitometric techniques for contrast quantitation, finding contrast agents capable of passing the lung capillary bed and measurement of right heart pressures using microbubble resonance techniques.

Densitometry↗

PubMed1989

Cavitation induced by asymmetric, distorted pulses of ultrasound: a biological test.

Prediction of the response of gaseous microbubbles to ultrasonic waves is complicated by the finite-amplitude distortion associated with large amplitude acoustic fields. Typical finite-amplitude pulses in medical applications consist of a sharp positive spike followed by a smaller, slowly varying negative pressure. In previous theoretical studies it was found that: (a) the peak-positive pressure is a very poor index of bubble response; (b) the peak-negative pressure typically underestimates the bubble response; (c) a better predictor of bubble response is the pressure amplitude of the fundamental in a Fourier series expansion of the distorted pulse. It is reported here that the killing of Drosophila larvae exposed to pulsed, symmetric, sinusoidal fields and to pulsed, asymmetric, distorted fields is consistent with these predictions.

Animals↗

PubMed1991

Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound.

Although no deleterious effects form diagnostic ultrasound have been reported in epidemiologic studies and surveys of widespread clinical usage (Ziskin and Petitti 1988), the conditions for the onset of transient cavitation must be investigated in the total evaluation of potential risks associated with diagnostic ultrasound applications. An extension of the results from the approximate theory developed by Holland and Apfel (1989) is applied in this paper to a population of nuclei to predict the onset of cavitation in host fluids with physical properties similar to those of biological fluids. From this analysis and from results of recent in vitro cavitation experiments, an index is developed which can gauge the likelihood of substantial microbubble growth in the presence of short-pulse, low-duty cycle diagnostic ultrasound.

Acoustics↗

PubMed1993

Quantitative echo contrast concentration measurement by Doppler sonography.

The hypothesis investigated in this study is that Doppler ultrasound can be used to make quantitative echo contrast concentration measurements in flow systems. Our motivation was to demonstrate the utility and some of the pitfalls of using scattered ultrasound intensity to quantify echo contrast in chambers and vessels. Doppler ultrasound was used rather than conventional imaging techniques because of its natural association with the assessment of flow in chambers and vessels. We compared the intensity of audio Doppler to various steady-state concentrations echo contrast in a carefully controlled in vitro flow system. A total of 62 paired audio Doppler intensity and echo contrast concentration measurements were made. A weak positive correlation was found between the absolute echo contrast concentration and audio Doppler intensity (r = 0.510, p = 0.001). The correlation was weak because of the many unknowns and effervescent nature of microbubble echo contrast agents. However, audio Doppler intensity was shown to correlate strongly with the relative concentration of echo contrast over short time periods (r = 0.958, p = 0.0001). The results show that Doppler intensity can be used to quantitatively measure the relative, but not the absolute concentration of echo contrast in in vitro flow systems.

Contrast Media↗

PubMed1994

A simple simulation for the visualisation of CSF flow in infants with hydrocephalus.

Cerebrospinal fluid (CSF) flow was demonstrated incidentally in our unit during the routine cranial colour Doppler examination of infants with hydrocephalus. Pulsed Doppler analysis of the flow jets within CSF has shown that for each CSF flow jet there is a characteristic sinusoidal wave pattern that decreases in amplitude at the end of each jet episode. Any activity that transiently elevates the intracranial pressure, such as crying, increased the intensity of this signal. A study was subsequently carried out to investigate the origin of these clinical observations of CSF flow. Using a simple flow phantom, experiments with degassed water demonstrated the transient production of a Doppler signal at a stenosis in an otherwise uniform bore tube. We postulate that in infants with obstructive hydrocephalus, high CSF velocities in excess of 25 cm/s are produced as a result of the pressure caused by the excess cerebrospinal fluid. In some instances fluid jets may give rise to the production of microbubbles that act as transient but extremely efficient reflectors for the ultrasound, thus enabling the visualisation of CSF flow in these patients.

Cerebrospinal Fluid↗

PubMed1996

Re-evaluation of the concept that high cell concentrations "protect" cells in vitro from ultrasonically induced lysis.

Diminution of apparent ultrasonic cell lysis in vitro with increasing cell concentration/volume fraction has often been observed. A substantial fraction of the cells may be lysed by ultrasound at low cell concentrations, but only a few percent are lysed when the concentration is a fraction of that of whole blood. This suggests that sonolysis of cells in vitro is suppressed by high cell concentrations, and, therefore, that sonolysis of cells in vivo is unlikely. We present the results of a retrospective analysis of experimental data and a theoretical analysis; these indicate that while relative sonolytic yield declines with increasing cell concentration, the "absolute" extent of ultrasound-induced lysis remains large. We find evidence that in vitro sonolysis of cells is limited at high cell densities by the number of available microbubbles and/or the number of cells each bubble may encounter and lyse prior to bubble "inactivation." Theory indicates the latter arises in consequence to the cell concentration-dependent formation of cell aggregates around pulsating bubbles.

Animals↗

PubMed1996

Hemolysis of albunex-supplemented, 40% hematocrit human erythrocytes in vitro by 1-MHz pulsed ultrasound: acoustic pressure and pulse length dependence.

The tested hypothesis was that ultrasound-induced hemolysis in blood supplemented with a microbubble contrast agent varies with ultrasound intensity and pulse duration. Human erythrocytes in autologous plasma containing 3.6% v:v Albunex microspheres were exposed to 1.07-MHz ultrasound pulses of 5 to 1000 mus at SPTP intensities of 0 to 1100 W/cm2. The dependence of hemolysis on the mechanical index (MI) value of the exposures was also examined. Ultrasound-induced hemolysis: (1) was evident at all pulse/intensity combinations; (2) increased generally with increasing pulse duration at constant intensity; and (3) increased with increasing MI at constant pulse duration. For pulses of 10 to 30 mus, ultrasound-induced hemolysis remained low (< or = 2%) at MI values < approximately 2 and increased sharply with further increase in MI; for 5-mus pulses, this abrupt increase in hemolysis was associated with a larger MI (approximately 3).

Adult↗

PubMed1988

Myocardial contrast echocardiography in humans. II. Assessment of coronary blood flow reserve.

The hypothesis that myocardial contrast echocardiography could be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a coronary artery was examined in nine patients and six dogs. All patients were undergoing cardiac catheterization and had single vessel coronary artery disease (greater than or equal to 85% stenosis of either the proximal left anterior descending or the left circumflex coronary artery); the six dogs had a critical stenosis of the left circumflex coronary artery. Three milliliters of sonicated Renografin-76 (mean microbubble size 6 micron) was injected into the left main coronary artery before and after intracoronary administration of papavarine, 6 to 9 mg. The beds supplied by the normal and stenotic vessels could not be differentiated during contrast echocardiography before injection of papavarine. However, after papavarine, the normal vascular bed showed significantly more contrast enhancement than did the bed supplied by the stenotic artery. This disparity in contrast enhancement made it possible to delineate the size of the bed perfused by the stenotic vessels. When quantitative analysis of the time-intensity curves obtained from the echocardiograms was performed in the dogs, the absolute values for the area under the curve, peak contrast intensity and curve width did not correlate with absolute blood flows measured with radiolabeled microspheres. However, the ratios of the areas under the curves derived from the two vascular beds before and after papavarine correlated well with the ratios of blood flows between the two beds during the same stages (r2 = 0.73 by linear regression and r2 = 0.85 by an exponential function). In comparison, the ratios of peak amplitudes and curve widths before and after papavarine had poor correlations with ratios of flows from the two beds (r2 = 0.18 and 0.02, respectively). In conclusion, myocardial contrast echocardiography can be used to simultaneously assess coronary blood flow reserve and the size of the perfusion bed supplied by a stenotic vessel.

Aged↗

PubMed1989

Left heart opacification with peripheral venous injection of a new saccharide echo contrast agent in dogs.

Opacification of the left heart chambers after venous injection of echo contrast agents with transpulmonary capabilities has been difficult to achieve because of a lack of availability of a biodegradable nontoxic agent that produces uniformly small microbubbles. SHU-508 is a new saccharide echo contrast agent that produces bubble sizes from 2 to 8 microns in diameter, capable of traversing the pulmonary capillary bed and resulting in left heart contrast. The echo intensity produced by this agent was compared with that of agitated saline solution, indocyanine green and SHU-454 (another experimental saccharide agent for right-sided contrast) during 136 injections in eight dogs. Videotaped two-dimensional echographic images were digitized and analyzed with the use of videodensitometry for peak right and left ventricular intensity, pulmonary transit times and time of persistence of contrast. The highest right ventricular intensity value (3,594 +/- 1,393) was achieved with SHU-508 (p less than 0.05 compared with the other agents). The right ventricular contrast seen with SHU-508 also persisted for a longer period (22.8 +/- 12 s) than with the standard agents (p less than 0.001). Left ventricular contrast with SHU-508 was visually evident in all 42 injections, whereas the peak left ventricular intensity was 35% as bright as that produced in the right ventricle by the same agent. Peak left ventricular intensity values from SHU-508 were compared with those from agitated saline solution injected from the pulmonary capillary wedge position in four dogs. SHU-508 produced brighter left ventricular intensity (1,281 +/- 607) compared with that obtained with the saline-wedge technique (p les than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Myocardial contrast echocardiography and the transmural distribution of flow: a critical appraisal during myocardial ischemia not associated with infarction.

OBJECTIVES: This study was undertaken to determine whether myocardial contrast echocardiography can be used to estimate the transmural distribution of flow. BACKGROUND: Myocardial contrast echocardiography has been shown to reliably measure average transmural blood flow during myocardial ischemia. However, there is controversy regarding its ability to determine the transmural distribution of flow. METHODS: The transmural distribution of flow was measured in 21 open chest anesthetized dogs with use of radiolabeled microspheres and sonicated albumin microbubbles (mean size 4.5 microns). In the 11 Group I dogs, myocardial contrast echocardiography was performed at baseline and during left anterior descending artery stenosis. In five of these dogs, it was also performed during left circumflex artery stenosis. In these dogs large (mean 12 microns) hand-agitated bubbles were also used. In the five Group II dogs, myocardial contrast echocardiography was performed before and 45 s after intracoronary injection of 6 mg of papaverine in the presence of a critical left circumflex artery stenosis. The five Group III dogs were studied during cardiopulmonary bypass at baseline and during left anterior descending artery stenosis. Off-line image analysis of the echocardiographic images was performed and time-intensity curves obtained from these images were correlated with radiolabeled microsphere-derived flows. RESULTS: The ratios of the parameters derived from the endocardium and epicardium during myocardial contrast echocardiography were found to correlate poorly (ranging from R2 = 0 to R2 = 0.35) with radiolabeled microsphere-derived endocardial/epicardial flow ratios over a wide range of flow ratios (0.01 to 2.58). These results were not influenced either by the location of the regions of interest (left anterior descending vs. left circumflex artery bed) or by the size of the bubbles (4.5 vs. 12 microns). CONCLUSIONS: Myocardial contrast echocardiography cannot be used to assess the transmural distribution of flow during myocardial ischemia not associated with infarction.

Animals↗

PubMed1993

Enhancement of Doppler flow signals in the left heart chambers by intravenous injection of sonicated albumin.

OBJECTIVES: The objective of this study was to evaluate the effect of a transpulmonary contrast agent on Doppler flow signals in the left heart chambers. BACKGROUND: Echo contrast agents are good ultrasound reflectors and could be used as Doppler signal enhancers. Sonicated albumin microbubbles are transpulmonary echo contrast agents and could enhance left heart Doppler signals after peripheral venous injection. METHODS: Thirty-one patients with various heart diseases without intracardiac shunts were assessed with Doppler echocardiography before and after injection of sonicated albumin. RESULTS: After an intravenous injection, pulsed Doppler signals of transmitral flow became more intense in all 16 patients examined, although flow velocity itself was not changed. In Doppler color flow imaging, the maximal mitral regurgitant signal area increased from 312 +/- 405 mm2 to 434 +/- 465 mm2, an average increase of 59 +/- 40% in all 17 patients with mitral regurgitation (p < 0.01). These effects were considered to be due to improvement of signal to noise ratio by the enhancement of Doppler flow signals. The duration of enhancement of pulsed Doppler transmitral flow signals was significantly longer than that of the left ventricular echocardiographic opacification (44 +/- 11 s vs. 17 +/- 7 s, p < 0.01). CONCLUSIONS: Intravenous injection of sonicated albumin can enhance the Doppler flow signals in the left heart chambers. This effect may be useful to improve the sensitivity of the Doppler system for detecting abnormalities of left heart blood flow such as mitral regurgitation.

Atrial Function, Left↗

PubMed1995

Myocardial contrast echo effect: the dilemma of coronary blood flow and volume.

Despite the useful information provided by myocardial contrast echocardiography, the meaning of myocardial contrast intensity remains elusive. This review is meant to define the contribution of physical and biologic factors in producing myocardial contrast and to elucidate the relative roles of coronary blood flow and intramyocardial blood volume in determining contrast effect. The main physical factors influencing the contrast echo effect include the properties of microbubbles as scattering elements (mainly their radius, compressibility, stability and concentration), electronic signal processing, instrument setting and contrast-induced signal attenuation. The effect of these factors can be limited by an appropriate experimental or clinical setup. Biologic factors are less easily controllable, and changes in coronary blood flow and alterations in myocardial blood volume appear to be the main determinants of myocardial contrast intensity. Moreover, these factors influence contrast intensity in opposite directions. Both the area under the time-intensity curve and the mean transit time of myocardial contrast are inversely related to coronary blood flow but directly related to myocardial vascularity and blood volume. Therefore, an increase in coronary flow not accompanied by an increase in myocardial vascularity and volume is accompanied by a decrease in the area under the curve and mean transit time of contrast. Conversely, an increase in coronary flow mediated by augmented myocardial vascularity and volume will produce an increase in the area under the curve and mean transit time. A better understanding of the physical and biologic determinants of contrast echo intensity will be fundamental in the clinical application of new agents and technologies.

Blood Flow Velocity↗

PubMed1995

Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropropane-exposed sonicated dextrose albumin.

OBJECTIVES: The purpose of this study was to determine whether intravenous dextrose albumin sonicated with a commonly used gas of low blood solubility and diffusivity (perfluoropropane) could identify acute myocardial ischemia and reperfusion. BACKGROUND: Recently, it has been demonstrated that dextrose albumin sonicated with gases that have low blood solubility and diffusivity results in microbubbles capable of consistently producing myocardial ultrasound contrast after intravenous injection. It remains to be determined, however, whether this contrast agent can visually detect the myocardial blood flow abnormalities seen with acute ischemia or stunned myocardium after reperfusion. METHODS: We gave intravenous injections (0.06 ml/kg body weight) of perfluoropropane-exposed sonicated dextrose albumin to 10 open chest dogs. The measured degree of myocardial contrast (0+ to 2+) and background-subtracted peak anterior myocardial videointensity produced from each injection were measured at three stages: 1) under baseline conditions, 2) during acute ischemia produced by a proximal left anterior descending coronary artery ligation lasting 10 to 120 min, and 3) after reflow was established. Coronary blood flow was monitored during all injections by using an ultrasound flow probe placed around the left anterior descending artery. RESULTS: Coronary blood flow ranged from 0 to 137 ml/min, and peak myocardial videointensity after intravenous administration of perfluoropropane-exposed sonicated dextrose albumin ranged from 0 to 70 gray scale U. There was consistent visual myocardial opacification in all dogs during baseline conditions and a visually evident decrease in myocardial contrast in the left anterior descending artery distribution after ligation. A relative increase in contrast in this same distribution after intravenous contrast agent administration occurred in 7 of the 10 dogs during reflow. Quantitatively, there was an excellent correlation in individual dogs between peak myocardial videointensity and coronary flow at all stages (mean correlation coefficient 0.95 +/- 0.04, range 0.87 to 0.99). CONCLUSIONS: Perfluoropropane-exposed sonicated dextrose albumin is an ultrasound contrast agent that can visually identify myocardial perfusion abnormalities from a peripheral venous injection.

Acute Disease↗

PubMed1996

Improved myocardial contrast with second harmonic transient ultrasound response imaging in humans using intravenous perfluorocarbon-exposed sonicated dextrose albumin.

OBJECTIVES: The objectives of this study were to determine whether a new method of ultrasound imaging (transient response imaging) could improve the myocardial contrast after intravenous injections of perfluorocarbon-exposed sonicated dextrose albumin microbubble contrast medium in humans. BACKGROUND: We have shown in animals that very low doses of intravenous contrast medium can produce transient but significantly better myocardial contrast when diagnostic ultrasound pulses are interrupted (delivered only once per cardiac cycle) instead of conventional 25- to 30-Hz frame rate imaging. METHODS: In 14 patients with normal rest wall motion, the peak myocardial contrast produced by transient response imaging was compared with that produced by conventional harmonic ultrasound imaging after injections of low doses (0.0025 to 0.01 ml/kg) of intravenous contrast medium. All studies were performed with second harmonic imaging (2.0 to 2.5 MHz-transmitted frequency). Blood pressure, oxygen saturation, respiratory rate and pulse were monitored before and after each injection. RESULTS: The intravenous contrast medium in the doses given produced no hemodynamic changes and no significant side effects in any patients. Overall, the mean (+/-SD) anterior and posterior myocardial contrast produced was significantly greater with transient response imaging than with conventional harmonic ultrasound imaging (anterior: 37 +/- 20 U transient response imaging vs. 18 +/- 14 U conventional harmonic imaging; posterior: 17 +/- 14 U transient response imaging vs. 5 +/- 5 U conventional; p< 0.01). With the sample size of 14 patients, the study had 80% power to detect a true difference of 18 U for anterior myocardial contrast and 90% power to detect a difference of 12 U for posterior contrast. Visually evident anterior or apical myocardial contrast was observed in 14 of 15 patients with transient response imaging but in only 7 patients with conventional harmonic imaging. Posterior or basal myocardial contrast was evident in 10 patients with transient response imaging but in only 1 patient with conventional harmonic imaging. CONCLUSIONS: Transient response imaging produces significantly better myocardial contrast than conventional harmonic imaging in humans and can be produced safely with minute quantities of intravenous perfluorocarbon.

Albumins↗

PubMed1990

Myocardial contrast echocardiography: cardiovascular effects of the contrast medium SHU 454 in dogs.

SHU 454 (Schering AG, Berlin, Federal Republic of Germany) is a new contrast agent that releases microbubbles with a median diameter of 3 microns into the circulation. During echocardiography, it permits visualization of myocardial blood flow (MBF) when given by intracoronary or aortic root injections. Its hemodynamic effects were investigated in anesthetized dogs with a view to application in humans. Cardiac effects were studied after intracoronary injections of 1 mL of SHU 454 (100 mg/mL). Twenty seconds after injection, MBF increased 35% and coronary vascular resistance decreased accordingly. The increase in MBF was not seen when the coronary bed was maximally dilated with intravenous dipyridamole. Peripheral effects were evaluated after 5 mL of SHU 454 (200 mg/mL) was injected into the aortic root, which gave the same myocardial echo contrast. Aortic pressure decreased 5%, and heart rate and dP/dt increased. To evaluate the effects of hypertonicity, SHU 454 was compared with five radiocontrast media and glucose. Its effects on MBF were similar to those of radiologic contrast media on an equal volume basis. Only 1 mL of intracoronary SHU 454, however, was required for myocardial contrast enhancement. The results suggest that visualization of the myocardium using SHU 454 or similar compounds for contrast echocardiography is a viable prospect.

Animals↗

PubMed2004

Usefulness of myocardial contrast echocardiography in predicting collateral blood flow in the presence of a persistently occluded acute myocardial infarction-related coronary artery.

Adequate collateral blood flow at rest can sustain myocardial viability despite persistent occlusion of the infarct-related artery (IRA) in acute myocardial infarction (AMI). This has therapeutic and prognostic implications. Studies addressing the value of intravenous myocardial contrast echocardiography (MCE) to detect collateral blood flow after AMI in humans are limited. Accordingly, 70 consecutive patients with AMI underwent low-power intravenous MCE using a Sonovue infusion 7 to 10 days after thrombolysis. Myocardial perfusion detected by MCE was analyzed (qualitatively and quantitatively) in the akinetic segments in 20 patients (29%) with an occluded IRA who subsequently underwent revascularization. Contractile reserve, which is a marker of myocardial viability, was assessed with low-dose dobutamine 12 weeks after mechanical revascularization. Of the 102 akinetic segments (32%), 37 (36%) showed contractile reserve. Contractile reserve was present in 24 of the 29 segments (83%) with homogenous contrast opacification and absent in 60 of the 73 segments (82%) with reduced/absent opacification. Quantitative peak contrast intensity, microbubble velocity, and myocardial blood flow were significantly higher (p <0.0001) in the segments with contractile reserve than in those without contractile reserve. Multiple logistic regression analysis using electrocardiographic, biochemical, and myocardial contrast echocardiographic markers of collateral blood flow showed that MCE (odds ratio 26.0, 95% confidence interval 6.3 to 108.0, p <0.001) was the only independent predictor of collateral blood flow as demonstrated by the presence of contractile reserve. MCE may thus be used as a reliable bedside technique for the accurate evaluation of collateral blood flow in the presence of an occluded IRA after AMI.

Collateral Circulation↗

PubMed2004

Reperfusion assessment using myocardial contrast echocardiography in patients with ST-segment elevation acute myocardial infarction.

In this study, 29 patients underwent myocardial contrast echocardiography after presentation with ST-segment elevation acute myocardial infarction but before coronary angiography using a continuous infusion of microbubbles and real-time imaging with a low mechanical index. Patients with transmural perfusion defects at presentation subsequently had much larger infarctions (as measured by peak creatine phosphokinase-MB fraction) than did those with normal perfusion, indicating that myocardial contrast echocardiography may be a useful means to determine adequacy of reperfusion after thrombolytic therapy and in the selection of patients for adjunctive treatment, such as "rescue angioplasty."

Contrast Media↗