Microbubble detection during cardiopulmonary bypass for open-heart surgery.
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Cardiac Surgical Procedures↗
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Results for “Microbubbles”
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Experimental air embolism: measurement of microbubbles using the Coulter counter.
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Embolism, Air↗
The effectiveness of various heart-lung machines in the elimination of microbubbles from the circulation.
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Animals↗
Microbubble embolism as a cause of computed tomographic changes of the brain after cardiopulmonary bypass.
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Age Factors↗
Ultrasonographic detection of testicular ischemia in a canine model using phospholipid coated microbubbles (MRX-115).
The purpose of this study was to determine if the sonographic contrast agent MRX-115 could improve the accuracy of Doppler ultrasonographic diagnosis of testicular ischemia. Testicular duplex ultrasonography was performed on six dogs before and after surgical ligation of the testicular artery, and before and after intravenous injection of MRX-115. Six radiologists blinded to experimental conditions rated the testicular blood flow. Receiver operating characteristics curves for conditions with and without administration of contrast agent were compared using Student's t-test for paired observations. Statistically significant differences were found both for the tests viewed individually (P = 0.003) and for the testes in comparison to the contralateral side (P = 0.0001). MRX-115 therefore is found to improve duplex sonographic evaluation of testicular ischemia.
Analysis of Variance↗
Discrepancies between catheter tip and tissue temperature in cooled-tip ablation: relevance to guiding left atrial ablation.
BACKGROUND: It is not known whether catheter tip temperatures with a cooled-tip ablation can be reliably extrapolated to estimate actual tissue temperatures. The relationship between catheter tip temperatures, tissue temperatures, power, and microbubble formation is not known. METHODS AND RESULTS: Nine dogs underwent 111 radiofrequency energy deliveries at the pulmonary vein ostia with a cooled-tip catheter. Catheter tip and tissue temperatures were markedly discrepant. Catheter tip temperature plateaus at 36 degrees C to 39 degrees C with increasing power, whereas tissue temperature increases to a mean of 75+/-3 degrees C at 45 W (maximum temperature >100 degrees C). Seventy-two energy deliveries were performed, titrating power to microbubble formation guided by intracardiac echocardiography. Type I and II microbubble formation occurred in 45 (63%) and 19 (26%) ablations, respectively. Type I microbubble emergence occurred at lower powers (21+/-8 versus 26+/-4 W; P=0.05), catheter tip temperatures (38+/-5 degrees C versus 48+/-10 degrees C; P=0.02), and tissue temperatures (65+/-19 degrees C versus 81+/-9 degrees C; P<0.001) than type II microbubble formation. Maximum impedance decreases during ablation before microbubble formation were less with type I microbubble (20+/-9 versus 37+/-11 Omega; P<0.001) compared with type II microbubbles. One quarter of type I microbubbles abruptly transitioned to type II microbubbles with significant changes in power or catheter tip temperature. No microbubbles were seen in 19 ablations (26%) despite powers up to 26+/-9 W and tissue temperatures up to 81+/-17 degrees C. CONCLUSIONS: Catheter tip and tissue temperatures are markedly discrepant during cooled-tip ablation. Type I and II microbubble formation occurs at overlapping power and catheter tip and tissue temperature ranges. Neither the absence of microbubbles nor the presence of type I microbubble formation ensures against excessive tissue heating. The appearance of microbubbles may indicate possible tissue overheating and signal a need to decrease energy.
Animals↗
Targeted ultrasound contrast agents: in vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx.
An ultrasound-based molecular imaging technique capable of detecting endothelial cell markers of inflammation may allow early, non-invasive assessment of vascular disease. Clinical application of targeted, acoustically-active microbubbles requires optimization of microbubble-endothelial adhesion strength to maximize image signal-to-noise ratio, as well as the ability to discern the degree of inflammation along a continuum of dysfunction. Accordingly, we hypothesized that adhesion of intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles is dependent on the degree of endothelial inflammation, and that microbubbles multi-targeted to both ICAM-1 (via anti-ICAM-1 antibodies) and selectins (via sialyl Lewisx) demonstrate greater adhesion strength than microbubbles targeted to either inflammatory marker alone. In a radial flow chamber, microbubbles were perfused across endothelial cells activated with interleukin-1beta to four different levels of inflammation, as assessed by quantitative ICAM-1 expression. ICAM-1-targeted microbubble adhesion strength increased with increasing degree of inflammation, with a relationship that was both positive and linear (r > 0.99). Microbubble adhesion strength was significantly higher for the multi-targeted microbubbles than either of the single-targeted microbubbles. These data thus demonstrate that multi-targeting of contrast microbubbles may offer improved adhesion characteristics, allowing for greater sensitivity to inflammation. Furthermore, the adhesion strength of targeted microbubbles is linearly dependent on the degree of inflammation, suggesting that targeted ultrasound imaging may offer differentiation between various degrees of endothelial dysfunction, and thus detect not only the presence, but also the severity of inflammatory disease processes.
Biomarkers↗
Italian Society of Cardiovascular Echography (SIEC) Consensus Conference on the state of the art of contrast echocardiography.
Part 1: Technical and methodological issues. Contrast echocardiography is based on the use of gas microbubbles. The size, gas composition and shell structure of the microbubbles modify their stability, resistance to pressure and scattering behavior. A proposed classification of contrast agents is based on the modalities of production of microbubbles (galenic or industrial); the industrial agents are divided into three generations depending on their characteristics. Following venous administration, the industrial microbubbles behave as intravascular free-flowing tracers and this is fundamental for their use in perfusion studies. When insonated at a low acoustic pressure, microbubbles show a linear behavior and can be used for signal amplification. At intermediate acoustic pressures microbubbles resonate and produce a harmonic signal that is detectable by new scanners. Higher acoustic pressures cause microbubble disruption with emission of a transient acoustic signal. The available contrast agents behave differently in an ultrasound field. Part 2: Safety of contrast echocardiography. Galenic contrast agents were tested in many studies for intracoronary and intravenous injection and no clinically relevant side effects were detected. The intravenous injection of industrial contrast agents is safe in all conditions, even in acute coronary syndromes. The interaction between ultrasound and microbubbles produces energy with potential effects on tissue for inertial cavitation and acoustic current production. These effects seem particularly interesting for the therapeutic applications of contrast echocardiography, but they do not appear to have clinically relevant effects. Part 3: Experimental studies. Experimental studies in contrast echocardiography are designed to induce, in animal models, acute myocardial infarction and coronary artery stenosis and to evaluate the differences in blood flow. The risk area and infarct area are well visualized with serial contrast agent infusion. No-reflow after coronary occlusion is a well-known phenomenon and is detectable at contrast echocardiography. Different degrees of induced coronary stenosis cause differences in the regional flow rate. The results of contrast echocardiographic studies are comparable with those of other invasive flow measurements. Caution must be used to transfer the knowledge acquired from animal studies to the clinical arena, owing to both methodological and anatomical differences. Part 4: Enhancement of Doppler signal and coronary flow study. The anterior descending coronary artery flow is detectable in almost all patients, and the posterior descending coronary artery in about 70%. The coronary flow reserve can be measured by injection of a vasodilator agent (dipyridamole or preferably adenosine) with a success rate of almost 100 % for the anterior descending but only 50 % for the posterior descending coronary artery. Data from transthoracic studies are comparable with those of Doppler flow wire. The fields of application presently include the evaluation of acute myocardial infarction, the short- and long-term results of percutaneous coronary interventions and coronary grafts, and the study of the microcirculation in several clinical conditions where the coronary flow reserve may be reduced, such as in syndrome X, hypertension, hypercholesterolemia or diabetes. Part 5: Endocardial border enhancement. Opacification of the left ventricle is the main indication to contrast echocardiography that, in this setting, is principally used to improve endocardial border delineation. This allows accurate evaluation of left ventricular volumes and function, increasing the role of echocardiography for the quantitative study of the left ventricle. Other indications for left ventricular opacification are the identification of intraventricular thrombosis, non-compaction of the left ventricle and heart rupture. In this respect, industrial second-generation contrast agents are more useful. The most appropriate patients for contrast echocardiography are those with a poor or suboptimal acoustic window, in whom a predictable diagnostic and prognostic usefulness of the procedure is expected. If appropriately used, contrast echocardiography is a cost-effective technique, although lack of reimbursement presently limits its use. Part 6: Use of contrast agents during stress echocardiography. Contrast agents during stress echocardiography may be used to improve the diagnostic accuracy of the test and to study myocardial perfusion. The diagnosis of ischemia in stress echo relies on the operator's visual assessment of changes in contractility during stress. Contrast agents must be considered an important tool that improve image quality especially in patients with an intermediate or poor acoustic window and their use has been reported to be cost-effective in the few studies designed to this end. The evaluation of myocardial perfusion during stress is certainly one of the most important goals of contrast echocardiography. Preliminary data are interesting but there is still a number of methodological problems that currently hamper clinical application. Part 7: Myocardial perfusion. Echocardiography has the potential of visualizing microbubbles in the microcirculation by detecting stimulated acoustic emission, produced by high-energy applied ultrasound, or by detecting the harmonic signal produced by resonance of the microbubbles in a low-energy ultrasound field. In the first case images are triggered at increasing end-systolic intervals (intermittent imaging), whereas in the second case entire cardiac cycles are analyzed (real-time imaging). Continuous infusion is the preferred method of maintaining a large and constant microbubble concentration inside the microcirculation. Analysis of the perfusion signal may be made in the qualitative, semi-quantitative or quantitative mode. Quantitative analysis is based on the construction of videointensity-time curves to study the refilling phase after complete microbubble destruction. There are not enough data in the literature showing the additional role of quantitative analysis for clinical purposes. Thus, at present, quantitative softwares should be considered as research tools. Conversely, there is a general consensus based on experimental and clinical studies on the use of myocardial contrast echo in patients with acute myocardial infarction by means of qualitative or semi-quantitative analysis. Important information on the infarct area extension, on the efficacy of reperfusion therapy, on the presence and extension of the no-reflow phenomenon and on the extent of residual tissue viability may be derived from the routine use of myocardial contrast echo. The reference technique still remains myocardial scintigraphy even though many theoretical problems are being discussed. Part 8: Implementing ultrasound contrast in the echocardiography laboratory. Contrast echocardiography should be considered an extension of the existing echocardiographic examination. Standard laboratory equipment is sufficient to run a contrast echocardiography program. However, cultural and technological upgrading is mandatory to obtain good results in contrast echocardiography. Intravenous infusion is easier during stress echocardiography than during rest study, because the time and cost for the venous line are comprised. In this setting, the cost-effectiveness for the addition of contrast agent is optimal, but patient selection is a critical point. The economic issue (contrast agent and personnel costs, and time needed) of contrast echocardiography determines the fact that without adequate reimbursement there is no incentive to perform the procedure.
Animals↗
Ultrasound contrast agents: basic principles.
INTRODUCTION: Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Levovist by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. THE BASIC PRINCIPLES OF ECHOCONTRAST AGENTS: The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. SECOND HARMONIC IMAGING: As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depending on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 microm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. CONCLUSIONS: The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities
Albumins↗
Targeting of ultrasound contrast material. An in vitro feasibility study.
PURPOSE: It would be beneficial to design a targetable microbubble ultrasound contrast agent that would selectively bind to the areas of interest in the body and enhance the target organ in the ultrasound examination. MATERIAL AND METHODS: We have studied the feasibility of targeting in a model system. We used avidin and biotin as a model ligand-receptor pair. Avidin was adsorbed on the surface of polystyrene, and biotin derivative was attached to microbubble shells. After removal of unincorporated biotin from the microbubbles, they were allowed to come in contact with avidin-coated or albumin-coated plastic. Unbound bubbles were washed by a stream of water. RESULTS: Binding of microbubbles to the surface occurred selectively in the areas where avidin layer was deposited. Binding of microbubbles to avidin layer was dependent on the amount of biotin incorporated in the microbubble shell. Presence of free biotin blocked targeting completely. Acoustic studies were performed using a custom-built ultrasound measurement apparatus and an ultrasound medical imaging system. Microbubble-coated areas of the plastic dish were clearly visualized with ultrasound imaging. A strong backscattered signal was obtained for microbubble surface densities as low as 3%. CONCLUSION: Microbubbles have been selectively targeted via a ligand-receptor system in vitro. Firm binding of microbubbles to avidin-coated surface has been achieved. Microbubbles deposited on the target were visualized with ultrasound imaging systems.
Animals↗
Flow dynamics of QW7437, a new dodecafluoropentane ultrasound contrast agent, in the microcirculation: microvascular mechanisms for persistent tissue echo enhancement.
OBJECTIVES: The purpose of this study was to test the hypothesis that a subgroup of QW7437 microbubbles, dodecafluoropentane-based ultrasound contrast microspheres, resides for prolonged periods in the microvasculature. BACKGROUND: QW7437 produces echo enhancement in myocardium which may persist relatively longer than opacification in the left ventricular cavity. The mechanism for this persistent enhancement remains unknown. METHODS: The transit of fluorescently labeled erythrocytes was examined by fluorescence intravital microscopy in the microvessels in five rat mesenteries. Ten rats were used to observe the behavior of fluorescently labeled QW7437 microbubbles in the mesenteric microcirculation. RESULTS: There was no significant change in erythrocyte velocity in the arterioles and venules after the administration of QW7437 microbubbles (0.05 ml/kg) preactivated by negative hydrodynamic pressure. Of 552 microbubbles observed in four arterioles and five capillaries, 549 (99.5%) passed without stoppage (> or = 0.1 s stoppage); only one stopped transiently in arteriole and two in capillaries, each for <0.5 s. Sixty-five of 478 microbubbles (13.6%) observed in six postcapillary venules 11 to 30 microm in diameter and 24 of 408 microbubbles (5.9%) in four venules 31 to 50 microm in diameter stopped transiently (0.1 to 180 s) with an attachment to venular endothelium; the remaining microbubbles passed through the venules without stoppage. CONCLUSIONS: Prolonged survival as microbubbles in the circulation and transient stoppage of a subgroup of microbubbles in the microvasculature, particularly in venules, are potential mechanisms for the persistent tissue echo enhancement by QW7437 microbubbles during contrast echocardiography.
Animals↗
Contrast ultrasound targeted drug and gene delivery: an update on a new therapeutic modality.
The effective delivery of intravascular drugs and genes to regions of pathology is dependent on a number of factors that are often difficult to control. Foremost is the site-specific delivery of the payload to the region of pathology and the subsequent transport of the payload across the endothelial barrier. Ultrasound contrast agent microbubbles, which are typically used for image enhancement, are capable of amplifying both the targeting and transport of drugs and genes to tissue. Microbubble targeting can be achieved by the intrinsic binding properties of the microbubble shells or through the attachment of site-specific ligands. Once microbubbles have been targeted to the region of interest, microvessel walls can be permeabilized by destroying the microbubbles with low-frequency, high-power ultrasound. A second level of targeting specificity can be achieved by carefully controlling the ultrasound field and limiting microbubble destruction to the region of interest. When microbubbles are destroyed, drugs or genes that are housed within them or bound to their shells can be released to the blood stream and then delivered to tissue by convective forces through the permeabilized microvessels. An alternative strategy is to increase payload volume by coinjecting drug- or gene-bearing vehicles, such as liposomes, with the microbubbles. In this manifestation, microbubbles are used for creating sites of microvessel permeabilization that facilitate drug or gene vehicle transport. Recent work in the emerging field of contrast ultrasound-based therapeutics, with particular emphasis on the delivery of drugs and genes to tissue through microvascular networks is reviewed.
Animals↗
The acoustic filter: an ultrasonic blood filter for the heart-lung machine.
Cardiopulmonary bypass-associated encephalopathy is thought to be due in part to continuous microembolization of the brain with gas microbubbles more than 40 microns in diameter during bypass. Current barrier filter technology cannot effectively remove such small microbubbles in fragile fluids such as blood. The design concepts for a new nonbarrier ultrasound-based fluid filtration system (an "acoustic filter") capable of filtering small microbubbles from blood are presented. The acoustic filter uses a field of high-intensity ultrasound to push microbubbles down an acoustic gradient, where they can be collected and removed. To test the filtration efficiency of the system, a Doppler ultrasound bubble detector was built. By monitoring the prefilter and postfilter Doppler signal an assessment of filtration efficiency was made. A suspension of stable albumin-encapsulated microbubbles (4 to 32 microns) were used as a model of the microbubble contaminants that might be found in the arterial return line of the heart-lung machine. Inactivated, the acoustic filter neither removed nor added microbubbles to the fluid. Activated, the acoustic filter provided total or near-total clearing of microbubbles. We conclude that the acoustic filter can remove microbubbles from a cardiopulmonary bypass-like apparatus.
Acoustics↗
Property and contrast-enhancement effects of lipid ultrasound contrast agent: a preliminary experimental study.
This work investigated the influence of some factors on the property in vitro of a self-made lipid ultrasound (US) contrast agent (LCA) and evaluated the relationship of acoustic pressure and enhancement effect in normal rabbit kidney parenchyma. In the in vitro studies, filling gas, solvent and concentration of LCA solution were investigated. Morphologic characteristics, concentration and mean diameter of microbubbles were considered as indices. In the in vivo studies, contrast-tuned imaging (CnTi) technique was used to investigate the enhancement effects in kidney parenchyma under nine acoustic pressure levels. Among the samples saturated with different filling gases, perfluoropropane (C(3)F(8)) resulted in the highest concentration of microbubbles and air, the lowest. Microbubbles filled with C(3)F(8) or sulfur hexafluoride (SF(6)) were quite stable and remained at a high level of concentration (above 2 x 10(9) microbubbles per mL) much longer than did air-filled microbubbles. Among the four solutions tested, 5% glucose solution and 0.9% saline solution showed higher initial concentrations and greater longevity than dextran 40 glucose solution (6%) or distilled water. The concentration of LCA solution had a positive correlation with the microbubble concentration. All microbubble samples under different test conditions remained shape-complete and no aggregation or fusion was observed. The mean diameter of microbubble samples was about 3.4 microm. Contrast intensity and longevity of CnTi enhancement in vivo showed an acoustic-pressure-dependent decrease. At 1 kPa, contrast intensity increased 224-fold (4.47/0.02) and the longevity of CnTi enhancement in the kidney parenchyma remained longer.
Air↗
Ultrasonic bubbles in medicine: influence of the shell.
Ultrasound contrast agents consist of microscopically small bubbles encapsulated by an elastic shell. These microbubbles oscillate upon ultrasound insonification, and demonstrate highly nonlinear behavior, ameliorating their detectability. (Potential) medical applications involving the ultrasonic disruption of contrast agent microbubble shells include release-burst imaging, localized drug delivery, and noninvasive blood pressure measurement. To develop and enhance these techniques, predicting the cracking behavior of ultrasound-insonified encapsulated microbubbles has been of importance. In this paper, we explore microbubble behavior in an ultrasound field, with special attention to the influence of the bubble shell. A bubble in a sound field can be considered a forced damped harmonic oscillator. For encapsulated microbubbles, the presence of a shell has to be taken into account. In models, an extra damping parameter and a shell stiffness parameter have been included, assuming that Hooke's Law holds for the bubble shell. At high acoustic amplitudes, disruptive phenomena have been observed, such as microbubble fragmentation and ultrasonic cracking. We analyzed the occurrence of ultrasound contrast agent fragmentation, by simulating the oscillating behavior of encapsulated microbubbles with various sizes in a harmonic acoustic field. Fragmentation occurs exclusively during the collapse phase and occurs if the kinetic energy of the collapsing microbubble is greater than the instantaneous bubble surface energy, provided that surface instabilities have grown big enough to allow for break-up. From our simulations it follows that the Blake critical radius is not a good approximation for a fragmentation threshold. We demonstrated how the phase angle differences between a damped radially oscillating bubble and an incident sound field depend on shell parameters.
Copper↗
Ultrasound/microbubble enhances foreign gene expression in ECV304 cells and murine myocardium.
Although viral vectors are efficient systems to transfer foreign genes into cells or target tissues, safety issues remain in relation to human gene therapy. Microbubbles currently used as ultrasound contrast agents have been applied in transfection of genes. This study was designed to test the transfection efficiency and the expression of exogenous gene mediated by ultrasound irradiation enhanced air filled albumin microbubbles in ECV304 cell line in vitro and the heart of the mouse in vivo. Air filled microbubbles (2.0-4.0 microm in diameter) were created by sonicating the mixture of human albumin, glucose, mannitol and special additive that was designed for stabilization. Plasmid DNA loading the reporter genes was gently mixed with microbubbles. The mixture of plasmid DNA and microbubbles was administrated to cultured ECV304 cells and BALB/c mice (tail vein injection) under different ultrasound/microbubble conditions, and then the transfection and expression efficiency were examined. The results both in vivo and in vitro demonstrated that microbubble with ultrasound irradiation could significantly elevate the exogenous gene expression as compared with microbubble or ultrasound only. Overall, the present study showed that the ultrasound-target microbubble destruction method enhanced the exogenous gene expression in vivo and in vitro, and provided a gene therapy way not only efficient but also easy to be manipulated and carried out in clinical.
Animals↗
Investigating the significance of multiple scattering in ultrasound contrast agent particle populations.
The majority of the existing models describing the behavior of microbubble ultrasound contrast agents consider single, isolated microbubbles suspended in infinite media. The behavior of a microbubble population is predicted by summing the results for single microbubbles and ignoring multiple scattering effects. The aim of this investigation is to determine the significance of multiple scattering in microbubble populations and establish whether an alternative approach is required. In the first part of the work, linear models are derived to identify approximately the conditions under which multiple scattering may be expected. A nonlinear model for sound propagation in a microbubble suspension then is developed and used to examine multiple scattering at higher insonation pressures. Broadband attenuation measurements are described for two different types of microbubble suspension (albumin encapsulated octofluropropane and copolymer encapsulated isobutane) to ascertain whether or not multiple scattering may be observed experimentally. The results from the simulation work indicate that multiple scattering effects would be discernible at moderate concentrations (10(6) microbubbles/ml) such as may be present in vivo. The effect upon attenuation in the suspension would be pronounced, however, only if the population contained a sufficient proportion of relatively large (> 4 microm radius) microbubbles excited at their resonance frequency. This also is found to be the case experimentally. These findings may have important implications for the characterization of ultrasound contrast agents and their use in quantitative diagnostic techniques.
Algorithms↗
The source of ultrasound contrast effect.
Evidence that microbubbles are the main sources of ultrasound contrast in injected solutions has been largely indirect. To investigate this directly, we examined freshly agitated indocyanine green, freshly agitated water, commercially prepared precision microbubbles (diameter 75 +/- 25 mu) in gelatin, carbonated water, "degassed" indocyanine green solution, and "degassed" water in one or more of four different assay systems. Only fluids with microbubbles produced ultrasound contrast. Injected contrast material rose in a water bath at a rate that identified it as being caused by microbubbles. Indocyanine green and gelatin surface tensions were measured and found to be low (43 dynes/cm2), thus explaining their tendency to stabilize the microbubbles that cause ultrasound contrast effect when injected and to hold foam after agitation. The force of hand injections (force similar to that used clinically through catheters and 19-gauge or 23-gauge needles) was below the force needed to cause cavitation or ultrasound contrast effect. Microbubble content could be quantified by the decrease in amplitude of the echo from a structure distant to the microbubbles. We conclude that that the ultrasound contrast effect seen in peripherally injected fluids is caused by microbubbles present in the injectant. The contrast is not due to cavitation at needle tips, and it can be quantified over a limited range. Improved design for a peripheral contrast agent is suggest.
Animals↗