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PubMed2005

Tissue Doppler imaging does not show infraclinical alteration of myocardial function after contrast echocardiography.

BACKGROUND: It has been previously suggested that simultaneous exposure of hearts to contrast and ultrasound can damage the myocardium and produce a transient decrease of the contractility in animals. Tissue Doppler imaging (TDI) is a useful tool to quantify the myocardial function with very high temporal resolution. AIM OF THE STUDY: The aim of the study was to test whether contrast echocardiography (CE) can cause alteration of the myocardial function by using tissue Doppler analysis. METHODS: Twenty-eight healthy patients (mean age: 44 +/- 22) underwent baseline echocardiography before and after 5 min of continuous intravenous infusion of Sonovue from the apical views, using an intermediate mechanical index (MI = 1). High frame rate images were acquired in tissue Doppler mode. Data were averaged over 3 cardiac cycles and analysed off-line before and after CE. RESULTS: There were no significant changes, before and after CE, in the peak systolic velocity (basal septum (BS): 6.2 +/- 2.2 vs 6.4 +/- 2.6; basal lateral (BL): 6.2 +/- 3.1 vs 6.4 +/- 3.3 cm/s), in the peak diastolic E velocity (BS: 5.4+/-1.8 vs 5.3+/-1.7; BL: 7.3+/-2.4 vs 7.7 +/- 3.2 cm/s), in the peak diastolic A velocity (BS: 6.3 +/- 1.9 vs 6.9 +/- 2.4; BL: 6.1 +/- 3.5 vs 6.2 +/- 2.5 cm/s), in the peak systolic strain (BS: 16 +/- 7 vs 17 +/- 7; BL: 12.6 +/- 5 vs 12.9 +/- 5%) and in peak systolic strain rate (BS: 1.3+/-0.6 vs 1.4+/-0.6; BL: 1.2+/-0.5 vs 1.21+/-0.51 1/sec). CONCLUSIONS: Our data suggest that CE does not cause alterations in the myocardial function as assessed by tissue Doppler imaging. CE, even with high MI settings, usually used for left ventricular opacification, can be safely performed.

Adult↗

PubMed2005

Safety: the heart of the matter.

An integral part of evaluation of cardiac disease in modern day medicine is echocardiography. It has made great strides since the initial collaboration of Dr. Helmut Hertz and Dr. Inge Edler. In its modern day form, echocardiography maintains a legacy of a bedside utility while adopting many of the technologic advances ushered in by the digital era. As a result, it boasts a broad and growing spectrum of application including routine use in primary cardiac diagnosis and screening, therapeutic assessment, and guidance of interventional and surgical procedures. With the advent of ultrasound contrast agents it is now arguably the most complete 'one-stop' investigational tool to assess cardiac structure, function and perfusion. However, has it maintained its safety profile? The familiar and oft quoted dictum in medicine of "first do no harm" is of great importance for any diagnostic tool and patient safety should remain a primary consideration for any new investigational technique. In this issue Cosyns' et al. have examined whether some of the theoretical and in vitro experimental concerns surrounding myocardial injury during and following contrast echocardiography result in any detectable change in cardiac function.

Cardiomyopathies↗

PubMed2006

Effect of air bubbles in the coupling medium on efficacy of extracorporeal shock wave lithotripsy.

OBJECTIVES: Replacement of the water bath by a water cushion in newer lithotriptors introduces an acoustic interface and an ideal coupling agent is required to prevent energy loss at this interface. We aim to study the effect of bubbles in the coupling media on efficacy of extracorporeal shock wave lithotripsy (ESWL) by an in vitro experiment. METHODS: Using a standardised in vitro model 40 artificial stones were randomly treated on Modulith SLK lithotriptor using either conventional ultrasound gel (high bubble content) before and after displacing visible bubbles, a thin ultrasound gel (Therasonic) or silicon oil (both with negligible bubbles). Percentage area covered by bubbles in each case and the diameters and depth of crater created in each stone were measured by two blinded observers to determine the correlation between the bubble contents and disintegration efficacy. In vivo effect of two ultrasound gels was compared in terms of pain scores and stone fragmentation rates in ten patients treated with both gels. RESULTS: Volume of the craters was significantly greater with the Therasonic gel (102.4+/-33.4 mm3) or silicon oil (98.8+/-9.8 mm3) than the conventional ultrasound gel (49.2+/-32.6 mm3). But it was greatest (p<0.001) with ultrasound gel without bubbles (163.5+/-22.6 mm3). Depth and volume of the stone crater increased significantly with decreasing bubble contents of gel (p<0.001). Compared to standard ultrasound gel, patients treated with Therasonic gel reported significantly higher pain scores (median 3.5 vs. 8.0; p<0.001). CONCLUSIONS: Efficacy of ESWL is significantly correlated to air bubbles within the coupling gel and can be improved significantly by eliminating the bubbles from the coupling medium.

Air↗

PubMed2005

Use of ultrasound contrast agents for gene or drug delivery in cardiovascular medicine.

The clinical utility of ultrasound contrast agents has been established in diagnostic echocardiography. Recently, the use of such agents has been promoted for transport and delivery of various bioactive substances, thus providing a technique for non-invasive gene therapy and organ-specific drug delivery. In this review, we give a critical update of published studies using ultrasound contrast agents for therapeutic use. We discuss the potential applications and limitations of this technique and suggest future applications in cardiovascular medicine.

Cardiovascular Diseases↗

PubMed2005

On-demand release by ultrasound from osmotically swollen hydrophobic matrices.

Ethylene-vinyl acetate copolymer (EVAc) based controlled release systems are composed of a continuous hydrophobic polymer phase and of dispersed solid drug particles. In matrices with high drug loadings (> or =50%) most drug particles are interconnected. Thus, when these matrices are immersed in water, release rates are relatively high. In matrices with low drug loadings (<40%) most drug particles are isolated within the continuous hydrophobic polymer matrix. Thus, release rates are very low. Matrices containing water soluble particles at a low loading swell intensely after immersion in water; this is caused by the osmotic force of the isolated particles which causes the water to permeate into the hydrophobic polymer. The enclosed drug particles absorb water, and at the end of the swelling process the matrices consist of an immense number of fluid pockets containing dissolved drugs. In attempt to develop on-demand release systems, we studied the effect of ultrasound (US) on the release rates of these swollen matrices. We found that low-frequency ultrasound (20 kHz) reversibly increased the release rates from these swollen matrices by a factor of 30-500, in contrast to the unswollen matrices, where the release rates increased only by a factor of 2-3. Unswollen and swollen matrices react differently to US, as unswollen matrices contain drug particles which absorb ultrasound on the surface of the matrices, causing ultrasound attenuation. On the other hand, swollen matrices contain a compact arrangement of fluid pockets separated from each other by thin membranes containing a solution of the dissolved drug, therefore ultrasound penetrates through the matrix volume. Ultrasound penetration causes tearing of these membranes within the matrices. As a result, the fluid pockets interconnect, and drug molecules diffuse out through these interconnected pockets.

Drug Carriers↗

PubMed2005

Ultrasound of the liver.

This article summarizes the recent advances in ultrasound imaging of the liver, especially contrast-enhanced imaging. Contrast-enhanced ultrasound has dramatically changed the role of ultrasound in liver tumor characterization, detection, and other applications. Available ultrasound contrast agents, agents under development, contrast-specific imaging techniques, and its applications in liver imaging are discussed.

Contrast Media↗

PubMed2003

Ultrasonic scattering cross sections of shell-encapsulated gas bubbles immersed in a viscoelastic liquid: first and second harmonics.

The oscillations of gas bubbles, without shell, immersed in viscoelastic liquids and driven by an acoustic wave have been the subject of several investigations. They demonstrate that the viscosity coefficient and the spring constant of the liquid have significant influence on the scattering cross section of the gas bubble. For shell-encapsulated gas bubbles, the investigations have been concentrated to bubbles immersed in a pure viscous liquid. This present work computes the ultrasonic scattering cross section, first and second harmonics, of shell-encapsulated gas bubbles immersed in a viscoelastic liquid. The theoretical model of the bubble oscillation is based on the generalized Rayleigh-Plesset equation of motion of a spherical cavity immersed in a viscoelastic liquid represented by a three-parameter linear Oldroyd model. The scattering cross section is computed for Albunex type of bubble (shell thickness=15 nm, shell shear viscosity=1.77 Pas, shell modulus of rigidity=88.8 MPa) irradiated by a 3.5 MHz ultrasonic pressure wave with an amplitude of 30 kPa. The results demonstrate that encapsulated bubbles respond independently of the surrounding liquid being pure viscous or viscoelastic as long as the surrounding liquid shear viscosity is as low as 10(-3) Pas. Nevertheless, for higher shear viscosities, the bubble responds differently if the surrounding liquid is pure viscous or viscoelastic. In general, the scattering cross sections of first and second harmonics are larger for the viscoelastic liquid.

Elasticity↗

PubMed2005

Bubble oscillation and inertial cavitation in viscoelastic fluids.

Non-linear acoustic oscillations of gas bubbles immersed in viscoelastic fluids are theoretically studied. The problem is formulated by considering a constitutive equation of differential type with an interpolated time derivative. With the aid of this rheological model, fluid elasticity, shear thinning viscosity and extensional viscosity effects may be taken into account. Bubble radius evolution in time is analyzed and it is found that the amplitude of the bubble oscillations grows drastically as the Deborah number (the ratio between the relaxation time of the fluid and the characteristic time of the flow) increases, so that, even for moderate values of the external pressure amplitude, the behavior may become chaotic. The quantitative influence of the rheological fluid properties on the pressure thresholds for inertial cavitation is investigated. Pressure thresholds values in terms of the Deborah number for systems of interest in ultrasonic biomedical applications, are provided. It is found that these critical pressure amplitudes are clearly reduced as the Deborah number is increased.

Elasticity↗

PubMed2005

Stability of an encapsulated bubble shell.

The stability of an encapsulated bubble filled with gas is studied where gas is allowed to diffuse out of the bubble. A mechanistic model that takes into account shell stiffness and surface tension is considered. A critical shell radius for loss of mechanical stability is derived based on a technique adapted for small radius, where surface tension effects become substantial. A new parameter is defined that determines the relative importance of surface tension forces and shell stiffness for shell stability. The developed technique allows to predict, for a given bubble population and gas saturation level of the surrounding liquid, a range of bubble sizes which may collapse in time. Surface tension effects are dominant in determining the critical radius but have a negligible effect on the minimal radius for collapse. The influence of the surface tension on the stability of the shell is illustrated for Optison, a typical ultrasound contrast agent.

Computer Simulation↗

PubMed2006

Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent.

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 microm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 degrees C vs. 37 degrees C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005-0.13 ml/kg). Quantitative in vivo dose-responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (approximately 4 dB) was observed at 25 degrees C over 20 min of insonation at 5 MHz but at 37 degrees C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T(g)).

Acoustics↗

PubMed2006

Influence of dissolved-air concentration on spatial distribution of bubbles for sonochemistry.

The pulsation of ultrasonic cavitation bubbles at various dissolved-air concentration in a sonochemical reaction field of standing-wave type is investigated experimentally by laser-light scattering. When a thin light sheet, finer than half the wavelength of sound, is introduced into the cavitation bubbles at an antinode of sound pressure, the scattered light intensity oscillates. The peak-to-trough light intensity is correlated with the number of bubbles that contribute to the sonochemical reaction. It is shown that as the dissolved air concentration becomes higher, the weighted center of the spatial distribution of the peak-to-trough intensity tends to shift towards the liquid surface. At higher concentration of the dissolved air, a great deal of bubbles with size distribution generated due to coalescence between bubbles disturbs sound propagation to change the sound phase easily. A standing wave to trap tiny oscillating bubbles is established only at the side which is nearer to the liquid surface. Also at higher concentration, liquid flow induced by drag motion of bubbles by the action of radiation force becomes apparent and position-unstable region of bubble is enlarged from the side of sound source towards the liquid surface. Therefore, the position of oscillating bubbles active for sonochemical reaction is limited at the side which is nearer to the liquid surface at higher concentration of the dissolved air.

Air↗

PubMed2006

The inception of cavitation bubble clouds induced by high-intensity focused ultrasound.

In many therapeutic applications of high-intensity focused ultrasound (HIFU) the appearance of cavitation bubbles is unavoidable, whereas the dynamics of the bubbles induced by HIFU have not been clarified. The objective of the present work is to observe the inception process of cavitation bubble clouds generated by HIFU transducer in water using high-speed photography. Sequential images captured within 600 micros after the onset of ultrasound transmission show the dynamics of cavitation bubbles' generation, growth, deformation, expansion and collapse in the focal region. However, when the observation time is narrowed to the initial 145 micros, both the still and streak images reveal that the cavitation bubbles astonishingly stay stable in the focal region for at least 60 micros. The results imply that through adjusting the HIFU exposure time while other physical parameters are appropriately chosen, it might be possible to control the generation of stable cavitation bubbles locally in the focal region.

Dose-Response Relationship, Radiation↗

PubMed2006

Observation of fluorescence emissions from single-bubble sonoluminescence in water doped with quinine.

Sonoluminescence is a phenomenon involving the transduction of sound into light. The detailed mechanism as well as the energy-focusing potentials are not yet fully explored and understood. So far only optical photons are observed, while emissions in the ultra-violet range are only inferred. By doping the fluorescent dye quinine into water with dilute sulphuric acid, the high energy photons can be converted into the optical photons with slower decay constants. These sonoluminescence and fluorescent emissions were observed in coincidence, and the emitted signals of the two modes can be differentiated by their respective timing profiles. Plans for using this technique as a diagnostic tool to quantitatively study ultra-violet and other high energy emissions in sonoluminescence are discussed.

Dose-Response Relationship, Radiation↗

PubMed2006

Modeling of interaction between therapeutic ultrasound propagation and cavitation bubbles.

In medical applications of high intense focused ultrasound the mechanism of interaction between ultrasound waves and cavitation bubbles is responsible for several therapeutic effects as well as for undesired side effects. Based on a two-phase continuum approach for bubbly liquids, in this paper a numerical model is presented to simulate these interactions. The numerical results demonstrate the influence of the cavitation bubble cloud on ultrasound propagation. In the case of a lithotripter pulse an increased bubble density leads to significant changes in the tensile part of the pressure waveform. The calculations are verified by measurements with a fiber optical hydrophone and by experimental results of the bubble cloud dynamics.

Computer Simulation↗

PubMed2004

Optical monitoring of ultrasound-induced bioeffects in glass catfish.

This study is an investigation of the therapeutic ultrasound (US) effects on the blood vessels of optically transparent fish in vivo. Although many investigators have characterized cavitation in vivo using remote-sensing methods (i.e., measuring the acoustic emissions caused by oscillating bubbles) very few have made direct observations of cavitation-induced damage. Anesthetized glass catfish, which are optically transparent, was injected with the contrast agent, Optison, and then insonified at pressures that ranged from 0.5-10 MPa (peak negative pressures). Two focused transducers were used in these experiments to cover a frequency range of 0.7-3.3 MHz. Sonications were pulsed with pulse durations of 100, 10, 1, 0.1 and 0.01 ms and a pulse repetition frequency (PRF) of 1 Hz. The entire length of one sonication at a specific pressure level was 20 s. An inverted microscope combined with a digital camera and video monitor were used optically to monitor and record US interaction with the blood vessels in the tail of the anesthetized fish at 200x magnification. The effects of the burst sonication were analyzed visually at each pressure level. For the 1.091-MHz sonications, the first type of damage that occurred due to the US interaction was structural damage to the cartilage rods that comprise the tail of the fish, and was characterized by a disintegration of the lining of the rod. Damage to the rods occurred, starting at 3.5 MPa, 3.1 MPa, 4.1 MPa and 5.5 MPa for the 100-ms, 10-ms, 1-ms and 100-micros sonications, respectively. The formation of large gas bubbles was observed in the blood vessels of the fish at threshold values of 3.8 MPa, 3.8 MPa and 5.3 MPa, for the 100-ms, 10-ms and 1-ms sonications, respectively. Neither gas bubble formation nor hemorrhaging was observed during 100-micros sonications. Bubble formation was always accompanied by an increase of damage to the rods at the area surrounding the bubble. At 1.091 MHz, petechial hemorrhage thresholds were observed at 4.1 MPa, 4.1 MPa and 6.1 MPa, respectively, for the three pulse durations. The thresholds for damage were the lowest for the 0.747-MHz sonications: they were 2.6 MPa for damage to the rods, 3.7 MPa for gas bubble formation and 2.4 MPa for hemorrhaging.

Acoustics↗

PubMed2003

Cell detachment method using shock-wave-induced cavitation.

The detachment of adherent HeLa cells from a substrate after the interaction with a shock wave is analyzed. Cavitation bubbles are formed in the trailing, negative pressure cycle following the shock front. We find that the regions of cell detachment are strongly correlated with spatial presence of cavitation bubbles. It is shown that the cavitation bubble collapse generates a transient high-speed flow along the substrate surface leading to rapid detachment of the cells. Flow trajectories are reconstructed from the video recordings using robust image-processing methods. From these trajectories, an estimate of the shear stress acting on the cells is obtained and the area of detachment is estimated with a kinetic model. Furthermore, it is suggested that the application of shock waves extends the known methods of cell detachment with the ability to control the process in space and time.

Cell Adhesion↗

PubMed2004

Membrane damage thresholds for 1- to 10-MHz pulsed ultrasound exposure of phagocytic cells loaded with contrast agent gas bodies in vitro.

Monolayers of mouse macrophage-like cells provide a model system for the study of bioeffects of pulsed ultrasound (US) activation of contrast agent gas bodies. In this study, the dependence of membrane damage on ultrasonic frequency was examined for gas bodies attached to the cells. The monolayers cultured on the inside of one window of an exposure chamber were incubated with 2% Optison (Amersham Health Inc., Princeton, NJ) and then rinsed to remove unattached gas bodies. The chamber was filled with culture medium plus 20% trypan blue stain solution and was mounted at the 3.8-cm focus of an US transducer in a 37 degrees C water bath. Transducers were used with center frequencies of 1.0, 2.25, 3.5, 5.0, 7.5 and 10.0 MHz. The 1-min pulsed exposures utilized two-cycle excitation with 1% duty cycle. After exposure, cells in the focal zone were scored for trypan blue dye exclusion, with stained nuclei indicative of cell membrane damage. Exposure-response functions were approximated by performing a series of exposures with peak rarefactional pressure amplitudes differing by a factor of radical 2 (i.e., 3 dB apart). Linear regressions were performed on selected data to determine a threshold pressure amplitude at each frequency. Thresholds ranged from 0.066 MPa at 1.0 MHz to 0.62 MPa at 10 MHz and were approximately proportional to the frequency. These thresholds are less than the pressure amplitudes needed for nucleation of inertial cavitation and have a different frequency dependence than the general Mechanical Index.

Albumins↗

PubMed2005

Cavitation cluster dynamics in shock-wave lithotripsy: part 1. Free field.

The spatiotemporal dynamics of cavitation bubble growth and collapse in shock-wave lithotripsy in a free field was studied experimentally. The lithotripter was equipped with two independently triggerable layers of piezoceramics. The front and back layers generated positive pressure amplitudes of 30 MPa and 15 MPa, respectively, and -10 MPa negative amplitude. The time interval between the launch of the shock waves was varied from 0 and 0.1 s, covering the regimens of pulse-modification (regimen A, delay 0 to 4 micros), shock wave-cavitation cluster interaction (B, 4 micros to 64 micros) and shock wave-gas bubble interaction (C, 256 micros to 0.1 s). The time-integrated cavitation activity was most strongly influenced in regimen A and, in regimen B, the spatial distribution of bubbles was altered, whereas enhancement of cavitation activity was observed in regimen C. Quantitative measurements of the spatial- and time-integrated void fractions were obtained with a photographic and light-scattering technique. The preconditions for a reproducible experiment are explained, with the existence of two distinct types of cavitation nuclei, small particles suspended in the liquid and residuals of bubbles from prior cavitation clusters.

Acoustics↗