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Effect of microbubble fragility on transit rate measurement by contrast echography.

We sought to propose a simplified method to measure flow velocity based on ultrasonic microbubble destruction, and investigated the effect of microbubble shell fragility on such measurement. Acoustic density (AD) from the second harmonic short axis image of flow was obtained at variable velocities (2 to 73 mm/s) in an in vitro model during long (1000 ms) and short (33 ms) interval ultrasound (US) pulsing, allowing complete and partial microbubble replenishment between pulses, respectively. Microbubbles with shell elastic modulus of 0.4 MPa and 16 MPa were tested. By shortening pulsing interval, AD diminished gradually, rather than abruptly, to a plateau level for both microbubbles. The extent of AD decay was greater for the fragile than the strong microbubbles. A linear relationship existed between the magnitude of AD decay and flow velocity only in the higher and lower velocity range for the fragile and the strong microbubbles, respectively. Thus, difference in contrast intensities during long and short pulsing intervals, respectively, allowing complete and partial replenishment may provide for velocity measurement, in which choice of optimal microbubble fragility for the range of velocity to measure may increase the accuracy.

Capsules↗

Mass-transfer properties of microbubbles. 1. Experimental studies.

Synthesis-gas fermentations have typically been gas-to-liquid mass-transfer-limited due to low solubilities of the gaseous substrates. A potential method to enhance mass-transfer rates is to sparge with microbubble dispersions. Mass-transfer coefficients for microbubble dispersions were measured in a bubble column. Oxygen microbubbles were formed in a dilute Tween 20 solution using a spinning disk apparatus. Axial dispersion coefficients measured for the bubble column ranged from 1.5 to 7.2 cm2/s and were essentially independent of flow rate. A laser-diffraction technique was used to determine the interfacial area per unit gas volume, a. The mass-transfer coefficient, KL, was determined by fitting a plug-flow model to the experimental, steady-state, liquid-phase oxygen-concentration profile. The KL values ranged from 2.9 x 10(-5) to 2.2 x 10(-4) m/s. Volumetric mass-transfer coefficients, KLa, for microbubbles with an average initial diameter of 60 microns ranged from 200 to 1800 h-1. Enhancement of mass transfer using microbubbles was demonstrated for a synthesis-gas fermentation. Butyribacterium methylotrophicum was grown in a continuous, stirred-tank reactor using a tangential filter for total cell recycle. The fermentation KLa values were 14 h-1 for conventional gas sparging through a stainless steel frit and 91 h-1 for microbubble sparging. The Power number of the microbubble generator was determined to be 0.036. Using this value, an incremental power-to-volume ratio to produce microbubbles for a B. methylotrophicum fermentation was estimated to be 0.01 kW/m3 of fermentation capacity.

Carbon Monoxide↗

Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration.

The microvascular rheology and extent of pulmonary retention of second-generation microbubble ultrasound contrast agents has not previously been well characterized. We assessed the microvascular behavior of Definity, a lipid-shelled microbubble agent containing perfluoropropane gas, using intravital microscopy of either rat spinotrapezius muscle or mouse cremaster muscle. Immediately after intra-arterial injection, which was performed to model pulmonary retention, larger microbubbles (> 5 microm) were entrapped within small arterioles and capillaries. The retention fraction of microbubbles was low (1.2% +/- 0.1%) and entrapment was transient (85% dislodged by 10 minutes), resulting in no adverse hemodynamic effects. Leukocyte or platelet adhesion at the site of entrapment was not seen. After intravenous injection, no microbubble entrapment was observed and the velocities of microbubbles in arterioles, venules, and capillaries correlated well with those of red blood cells. We conclude that after intravenous injection and pulmonary passage, the microvascular rheology of Definity microbubbles is similar to that of red blood cells. Microbubble entrapment within the pulmonary microcirculation after venous injection should be negligible and transient. These findings are important for establishing the safety of this agent.

Animals↗

Helium gas microbubbles. Experimental study on a new ultrasound contrast material.

PURPOSE: To evaluate histological changes and duration of enhancement after the intra-arterial injection of helium gas microbubbles in comparison with conventionally used carbon dioxide (CO2) microbubbles at US. MATERIAL AND METHODS: Four different doses of helium gas microbubbles (0, 0.1, 0.2 and 0.5 ml/kg) mixed with normal saline and own blood were injected into the celiac artery of 8 rabbits. After one week, autopsies were performed on all animals and histological changes in the liver, stomach and spleen were studied on hematoxylin-eosin stains. In addition, VX-2 tumor strains were transplanted into the femoral muscle in 5 other rabbits. Four weeks after transplantation, we catheterized the femoral artery and either CO2 or helium gas microbubbles were injected under US observation. We evaluated the duration of enhancement in the tumors with the two types of microbubbles. RESULTS: On histological evaluation, damage in hepatic cells as well as multiple areas of gastritis in the stomach were seen when a dose of 0.5 ml/kg of helium gas was used. Damage in the liver and stomach was slight at a dose of 0.2 ml/kg. The spleen was not damaged at doses of under 0.5 ml/kg. In the evaluation of tumor enhancement, the duration of enhancement with helium gas microbubbles ranged from 28 to 45 min (average 36 min) while that with CO2 ranged from 4 to 12 min (average 9 min) (p<0.01 at paired t-test). CONCLUSION: Intra-arterial injection of helium gas should not exceed 0.2 ml/kg: a dose of 0.5 ml/kg may cause damage to the liver and stomach. The duration of enhancement with helium gas microbubbles is significantly longer than that with CO2 microbubbles.

Animals↗

Are microbubbles free flowing tracers through the Myocardium? Comparison of indicator-dilution curves obtained from dye dilution and echo contrast using harmonic power Doppler imaging.

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

Animals↗

Effect of microbubble exposure to ultrasound on quantitation of myocardial perfusion.

BACKGROUND: The purpose of this study was to determine whether acoustic disruption of microbubbles in the left ventricular (LV) cavity prior to entry in the coronary circulation or their gradual destruction in the myocardium during myocardial contrast echocardiography (MCE) affects quantitative parameters of myocardial perfusion. METHODS: MCE was performed in 12 open chest dogs with both intermittent high-power imaging (IHPI) and real-time low-power imaging (RLPI). To assess the affects of microbubble destruction in the LV cavity, MCE parameters of myocardial perfusion were compared for imaging planes that included versus avoided the LV cavity. To assess the effects of gradual disruption of microbubbles in the microcirculation during RLPI, MCE parameters from frames acquired continuously were compared to that from acquiring only end-systolic frames. RESULTS: Destruction of microbubbles in the LV cavity did not alter perfusion data for either form of imaging unless RLPI was performed using long (6-frame) destructive pulse sequences. With RLPI, a gradual decay in microbubble signal occurred during their myocardial transit, the degree of which was related to the acoustic power. Signal decay during microbubble transit resulted in an overestimation of the microvascular blood velocity (beta-value) and an underestimation of the microvascular blood volume (A-value). CONCLUSIONS: MCE parameters of perfusion at low power can be significantly altered by microbubble destruction in the LV cavity and in the myocardial microcirculation during RLPI. Short microbubble destruction pulse sequences and imaging only at end-systole can reduce these effects.

Analysis of Variance↗

Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3.

BACKGROUND: Angiogenesis is a critical determinant of tumor growth and metastasis. We hypothesized that contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins expressed on the neovascular endothelium could be used to image angiogenesis. METHODS AND RESULTS: Malignant gliomas were produced in 14 athymic rats by intracerebral implantation of U87MG human glioma cells. On day 14 or day 28 after implantation, CEU was performed with microbubbles targeted to alpha(v)beta3 by surface conjugation of echistatin. CEU perfusion imaging with nontargeted microbubbles was used to derive tumor microvascular blood volume and blood velocity. Vascular alpha(v)-integrin expression was assessed by immunohistochemistry, and microbubble adhesion was characterized by confocal microscopy. Mean tumor size increased markedly from 14 to 28 days (2+/-1 versus 35+/-14 mm2, P<0.001). Tumor blood volume increased by approximately 35% from day 14 to day 28, whereas microvascular blood velocity decreased, especially at the central portions of the tumors. On confocal microscopy, alpha(v)beta3-targeted but not control microbubbles were retained preferentially within the tumor microcirculation. CEU signal from alpha(v)beta3-targeted microbubbles in tumors increased significantly from 14 to 28 days (1.7+/-0.4 versus 3.3+/-1.0 relative units, P<0.05). CEU signal from alpha(v)beta3-targeted microbubbles was greatest at the periphery of tumors, where alpha(v)-integrin expression was most prominent, and correlated well with tumor microvascular blood volume (r=0.86). CONCLUSIONS: CEU with microbubbles targeted to alpha(v)beta3 can noninvasively detect early tumor angiogenesis. This technique, when coupled with changes in blood volume and velocity, may provide insights into the biology of tumor angiogenesis and be used for diagnostic applications.

Animals↗

Relation between air-filled albumin microbubble and red blood cell rheology in the human myocardium. Influence of echocardiographic systems and chest wall attenuation.

BACKGROUND: We have previously shown that the intravascular rheology of sonicated air-filled albumin microbubbles is similar to that of red blood cells (RBCs) and that their myocardial transit rate is also similar to that of RBCs in the beating canine heart. In the present study, we tested the hypothesis that the myocardial transit rates of these microbubbles reflect those of RBCs in humans at different coronary flow rates. METHODS AND RESULTS: RBC and microbubble transit rates were measured in 17 patients undergoing coronary angiography: in 8, measurements were made only at rest, whereas in 9, they were performed both at rest and during a pacing-induced increase in coronary blood flow. A gamma-variate function was used to derive mean RBC and microbubble transit rates from the time-activity and time-intensity plots after the left main injection of RBCs and microbubbles, respectively. There was linear correlation between the myocardial transit rates with both tracers with the slope of the correlation determined by the specific echocardiographic system that was used. Microbubble transit rate consistently overestimated RBC transit rate due to artificial narrowing of the time-intensity curves caused by chest wall attenuation of the echocardiographic signal, which was confirmed through in vitro experiments. CONCLUSIONS: There is close correlation between air-filled albumin microbubbles and RBC rheology in the human myocardium. The use of these microbubbles in the cardiac catheterization laboratory could, therefore, provide further insights into myocardial blood flow/myocardial blood volume relations in humans.

Adult↗

Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin.

BACKGROUND: Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging. METHODS AND RESULTS: Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles. CONCLUSIONS: Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.

Animals↗

Microbubble-induced phospholipase C activation does not correlate with platelet aggregation.

The effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p < 0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p < 0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p < 0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p < 0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.

Aspirin↗

Augmentation of cardiac protein delivery using ultrasound targeted microbubble destruction.

Gas-filled microbubbles have become an important tool as ultrasonic contrast agents. We have previously shown that ultrasound-targeted microbubble destruction (UTMD) can direct plasmids to the heart. The aim of this study was to evaluate UTMD for protein delivery. Six different groups of rats received 1 microg of luciferase protein with varying protocols: (1) luciferase-loaded microbubbles and ultrasound; (2) luciferase only; (3) luciferase and ultrasound; (4) luciferase-loaded microbubbles; (5) unloaded microbubbles incubated with luciferase and ultrasound; (6) unloaded microbubbles with ultrasound followed by luciferase. Relative luminescence units per mg protein per s were determined in hearts and control organs. The rats that received ultrasound and luciferase-loaded bubbles showed a six-fold higher cardiac luciferase uptake compared with control groups that did not include bubbles. None of the other groups significantly augmented cardiac luciferase activity. We conclude that ultrasound-targeted microbubble destruction can substantially and noninvasively augment organ-specific delivery of proteins.

Animals↗

Effectiveness of lipid microbubbles and ultrasound in declotting thrombosis.

The objectives of this study were to determine the effectiveness of lipid-encapsulated microbubbles and ultrasound (US) in recanalizing arteriovenous graft thrombi and the effect that tissue attenuation has on the success rate. A total of 55 thrombotic occlusions were created in four canines. The thrombosed grafts were randomly treated with two different 1-MHz US intensities, low (0.4 to 0.6 W/cm(2)) and high (10 W/cm(2)). Intragraft microbubbles were compared with intragraft saline and with the same dose of microbubbles given IV. IV microbubbles were also given both in the presence and absence of a tissue-mimicking phantom. High-intensity US (10 W/cm(2)) with intragraft microbubbles produced significantly higher patency and flow scores than did US with saline (p < 0.01). US with IV microbubbles had higher success rates in recanalizing thrombosed grafts than did US alone at all intensities. Attenuation reduced the rate at which successful recanalization occurred at both low and high intensities. US and microbubbles are capable of recanalizing acute arteriovenous graft thromboses. Higher intensities may be needed in the presence of tissue attenuation.

Acute Disease↗

Ultrasound exposure can increase the membrane permeability of human neutrophil granulocytes containing microbubbles without causing complete cell destruction.

Activated polymorphonuclear neutrophil (PMN) granulocytes can bind and subsequently phagocytose microbubbles used as ultrasound (US) contrast agents. The purpose of the present study was to assess insonation effects on cell membrane integrity and metabolic activity of activated PMN. Furthermore, we investigated whether or not there is an acoustic threshold at which insonation of PMN results in increase of membrane permeability without causing complete cell destruction. PMN isolated from healthy volunteers were activated with phorbol myristate acetate (PMA) for 15 min to allow phagocytosis of albumin and lipid microbubbles and were subsequently exposed to US with a mechanical index between 0.15 and 1.8. Apoptosis, loss of membrane integrity and formation of cell fragments were evaluated by measurement of lactate dehydrogenase leakage and by double staining with annexin V and propidium iodide, using flow cytometry. Neutrophil superoxide anion generation was measured photometrically. Insonation of activated PMN in the presence of microbubbles amplified apoptosis and lactate dehydrogenase leakage and induced loss of membrane integrity and complete cell destruction with increasing acoustic pressures. The bioeffects observed by insonation with high mechanical indices (1.0 to 1.8), and particularly the formation of cell fragments, were significantly more pronounced in the presence of albumin microbubbles. Insonation in the presence of lipid microbubbles increased cell membrane permeability, but caused significantly less cell destruction and left the metabolic activity of activated PMN uninfluenced. Thus, both albumin and lipid microbubbles induce apoptosis and membrane injury during insonation of activated PMN. However, insonation in the presence of lipid microbubbles seems to influence cell viability to a smaller extent. This could be of advantage in the setting of US-guided local drug delivery. In this setting, increase of membrane permeability may allow bioactive substances to enter into cells, which survive the US treatment, and specifically modify their function.

Albumins↗

Mitral mechanical heart valves: in vitro studies of their closure, vortex and microbubble formation with possible medical implications.

OBJECTIVE: The goal of the present work was to create the closest possible in vitro fluid dynamic environment in which prosthetic mitral valves in the patients' hearts function, in order to demonstrate whether microbubbles are generated, and if yes, under what conditions and at which stage of the cardiac cycle. Microbubbles were observed in the blood of patients with mitral mechanical heart valves (MHV) by means of echocardiography. The phenomenon, often referred to as high-intensity transient signals (HITS), appears as bright, intense, high-velocity and persistent echoes detected by Doppler echocardiography at the instant of valve closure. The question is no longer whether microbubbles are being formed in patients with MHV. as an inherent aspect of their design, but rather how they evolve and when. The answer to this question was the objective of the present paper. METHODS: Hemodynamic conditions in which microbubbles were observed in patients with mitral MHV were simulated in our laboratory. We were able to describe the bubble formation process, as one consisting of nucleation and microbubble growth. While mild growth of nuclei is governed by diffusion, extensive growth of microbubbles is controlled by pressure drop during deceleration of the leaflets on the housing on the atrial side of the mitral MHV. RESULTS: The present study has shown that bubbles form in a fluid at the instant of closure of mechanical valves. The formation of vortices after valve closure, although clinically not yet observed, was also demonstrated in the present in vitro studies. We believe that impact of such vortices on the endothelial layer of the left atrial wall may have clinical significance. These two phenomena were not observed in bioprosthetic valves. CONCLUSIONS: As demonstrated, there exist two distinct phenomena characteristic of mechanical heart valves, which take place during valve closure, namely, that of vortex formation and that of microbubble growth. Both phenomena may have far reaching clinical implications.

Blood Flow Velocity↗

A novel microbubble construct for intracardiac or intravascular MR manometry: a theoretical study.

It has been demonstrated that gas-filled microbubble contrast agents, based on their volume changes, can serve as pressure probes in an MR field. It was recently reported that such an MR-based pressure measurement with microbubbles at 1.5 T must make use of microbubbles that have a volumetric magnetic susceptibility difference with the blood of at least 34 ppm in SI units. In this work, we show through analytical approximations and numerical simulations that such a microbubble formulation can be achieved by coating typical lipid-shelled microbubbles with particles of high dipole moment. Through finite-element simulations we demonstrate that the effective volumetric magnetic susceptibility of a coated microbubble is dependent on the radius, the shell volume fraction and the magnetic susceptibility of the particulates on the shell. Our calculations suggest that a suitable microbubble formulation which will be MR-sensitive to small pressure changes at 1.5 T must be 2-3 microm in radius and be uniformly coated with single-domain magnetic nanoparticles, such as magnetite, at shell volume fractions below 5%.

Arteries↗

Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications.

The use of microbubble contrast agents for general tissue delineation and perfusion enjoys steady interest in ultrasound imaging. Microbubbles as contrast materials require a small dosage and show excellent detection sensitivity. Targeting ligands on the surface of microbubbles permit the selective accumulation of these particles in the areas of interest, which show an up-regulated level of receptor molecules on vascular endothelium. Selective contrast imaging of inflammation, ischemia-reperfusion injury, angiogenesis, and thrombosis has been achieved in animal models. Ultrasound-assisted drug delivery and activation, performed by combining microbubble agent containing drug substances or coadministered with pharmaceutical agents (including plasmid DNA for transfection), has been achieved in multiple model systems in vitro and in vivo. Ultrasound and microbubbles-based targeted acceleration of the thrombolytic enzyme action already have reached clinical trials. Overall, microbubble targeting and ultrasound-assisted microbubble-based drug-delivery systems will offer a step toward the application of targeted personalized diagnostics and therapy.

Animals↗

Resonance frequency of microbubbles: effect of viscosity.

The transmitted frequency at which a gas bubble of millimeter or submillimeter size oscillates resonantly in a low-viscosity liquid is approximately equal to the undamped natural frequency (referred to as the Minnaert frequency if surface tension effects are disregarded). Based on a theoretical analysis of bubble oscillation, this paper shows that such an approximation cannot be validated for microbubbles used in contrast-enhanced ultrasound imaging. The contrast-agent microbubbles represent either encapsulated bubbles of size less than 10 microm or free (nonencapsulated) bubbles of submicron size. The resonance frequency of the microbubbles deviates significantly from the undamped natural frequency over the whole range of microbubble sizes due to the increased viscous damping coefficient. The difference between these two frequencies is shown to have a tremendous impact on the resonant backscatter by the microbubbles. In particular, the first and second harmonics of the backscattered signal from the microbubbles are characterized by their own resonance frequencies, equal to neither the microbubble resonance frequency nor the undamped natural frequency.

Blood Flow Velocity↗

Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro.

Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison or Sonazoid microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters.

Gels↗