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At least 253 records · Page 14Linked to original sources

PubMed2007

Frequency and pressure dependent attenuation and scattering by microbubbles.

The aim of this study was to evaluate experimentally the degree of pressure dependence of attenuation and scattering by microbubbles at low acoustic pressures with an empirical nonlinear model. In addition, the pressure dependency over a range of frequencies (1 to 5 MHz) has been studied. A series of transmission and scattering measurements were made with the microbubble SonoVue, using an automated system. Results show that, within the pressure range studied, attenuation as a result of the microbubble is pressure-dependent, whereas no such dependence of scattering was detectable. The pressure dependence of attenuation for SonoVue was found to be most significant at 1.5 MHz. The scattering is shown to be the highest at the lowest insonation frequency, around 1 approximately 1.25 MHz, and then decreases with frequency.

Humans↗

PubMed2006

Collapse and shedding transitions in binary lipid monolayers coating microbubbles.

We report on a fluorescence microscopy study of the monolayer collapse and shedding behavior due to shell compression during the dissolution of air-filled, lipid-coated microbubbles in degassed media. The monolayer shell was comprised of saturated diacyl phosphatidylcholine (C12:0 to C22:0) and an emulsifier, poly(ethylene glycol)-40 stearate. The morphologies of monolayer collapse structures and shed particles were monitored as a function of phospholipid acyl chain length (n) and temperature. The two components formed a single miscible phase when the phospholipid was near or above its main phase transition temperature, and collapse occurred via suboptical particles to vesicles (both were shed) and tubes as chain length increased. Conversely, two-phase coexistence was observed when the lipid was below its main phase transition temperature. For these bubbles, a transition from primary collapse to secondary collapse was observed. Primary collapse was observed as a loss of expanded phase due to vesiculation. Secondary collapse involved the rapid propagation of monolayer folds and simultaneous deformation. For very rigid monolayers, we observed substantial surface buckling with simultaneous nucleation and growth of folds. The folds merged at a single point or region, providing a conduit for the entire excess lipid to shed in a single event, and the bubble smoothed and became more spherical. These results are discussed in the context of general binary phospholipid collapse behavior, microbubble dissolution behavior, medical applications, and the dissolution behavior of natural microbubbles.

Hot Temperature↗

PubMed2006

Long-term stability by lipid coating monodisperse microbubbles formed by a flow-focusing device.

In this letter, the long-term stabilization of monodisperse microbubbles produced by flow focusing is demonstrated using lipid encapsulation. Fluorescence microscopy, high-speed camera imaging, and particle size analysis were used to investigate the roles of lipid phase behavior, dissolution, Ostwald ripening, and coalescence in the stability of microbubbles formed by flow focusing. It was found that these behaviors were controlled through compositional changes with respect to lipid, emulsifier, and viscosity agents. Microbubbles coated with lipid and PEG emulsifier in a viscous solution were found to contain an extremely narrow size distribution (diameter(av) = 51 microm, standard deviation = 4 microm), which was maintained for up to several months.

Microbubbles↗

PubMed2005

Targeting of VEGF-mediated angiogenesis to rat myocardium using ultrasonic destruction of microbubbles.

Myocardial angiogenesis mediated by human vascular endothelial growth factor 165 (hVEGF165) cDNA was promoted in rat myocardium using an in vivo-targeted gene delivery system known as ultrasound-targeted microbubble destruction (UTMD). Microbubbles carrying plasmids encoding hVEGF165, or control solutions were infused intravenously during ultrasonic destruction of the microbubbles within the myocardium. Biochemical and histological assessment of gene expression and angiogenesis were performed 5, 10, and 30 days after UTMD. UTMD-treated myocardium contained hVEGF165 protein and mRNA. The myocardium of UTMD-treated animals showed hypercellular foci associated with hVEGF165 expression and endothelial cell markers. Capillary density in UTMD-treated rats increased 18% at 5 days and 33% at 10 days, returning to control levels at 30 days (P<0.0001). Similarly, arteriolar density increased 22% at 5 days, 86% at 10 days, and 31% at 30 days (P<0.0001). Thus, noninvasive delivery of hVEGF165 to rat myocardium by UTMD resulted in significant increases in myocardial capillary and arteriolar density.

Animals↗

PubMed2006

The influence of acoustic transmit parameters on the destruction of contrast microbubbles in vitro.

In this study, the destruction of the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) was measured in vitro as a function of centre frequency (2-3 MHz), acoustic amplitude (0.66-1.6 MPa), pulse length (2-16 cycles) and PRF (0.5-8.0 kHz). Up to 82% of microbubbles were destroyed after exposure to a single 1.6 MPa acoustic pulse (16 cycles, 2.5 MHz and PRF of 1.0 kHz), while at a low amplitude of 0.66 MPa, fractional destruction increased gradually from 0 to 40% after exposure to 9 (identical) pulses. Fractional destruction increased from approximately 8 to 66% as pulse length was changed from 2 to 16 cycles following exposure to a single 2.5 MHz, 1.3 MPa pulse. As the PRF was increased from 0.5 to 8.0 kHz, shorter exposure time intervals (from 4.8 to 1.2 ms) were needed to achieve the same fractional destruction of 80%. Conversely, as the transmit frequency was increased from 2 to 3 MHz the fractional destruction decreased (by more than half within the first 3 pulses). The influence of changes in acoustic pressure and duty cycle on the destruction of Sonazoid microbubbles was highly statistically significant (p < or = 0.01) with a threshold around 0.67 MPa for a duty cycle of 0.0064. In conclusion, the fractional destruction increases with the duty cycle and the acoustic pressure amplitude and decreases with ultrasonic transmit frequency. Better understanding of the influence of the ultrasound transmit parameters on the destruction of contrast microbubbles should help improve existing contrast-assisted imaging modalities and may help develop new techniques for better use of contrast agents.

Contrast Media↗

PubMed2005

High-frequency, nonlinear flow imaging of microbubble contrast agents.

It has been shown that nonlinear scattering can be stimulated from microbubble contrast agents at high-transmit frequencies (14-32 MHz). This work was extended to demonstrate the feasibility of nonlinear contrast imaging through modifications of existing ultrasound biomicroscopy linear B-scan imaging instrumentation. In this study, we describe the development and evaluation of prototype coherent flow imaging instrumentation for nonlinear microbubble imaging using transmit frequencies from 10 to 50 MHz. Phantom validation experiments were conducted to demonstrate color and power flow imaging using nonlinear 10 MHz (subharmonic) scattering induced by a 20 MHz transmit frequency. In vivo flow imaging of a rabbit ear microvessel was successfully performed. This work indicates the feasibility of performing flow imaging at high frequencies using nonlinear scattering from microbubbles.

Animals↗

PubMed2004

Forced linear oscillations of microbubbles in blood capillaries.

A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.

Biomechanical Phenomena↗

PubMed2004

Evidence for spleen-specific uptake of a microbubble contrast agent: a quantitative study in healthy volunteers.

PURPOSE: To evaluate the pharmacokinetics of the microbubble contrast agent BR1. MATERIALS AND METHODS: Twenty healthy volunteers were injected via arm vein with a 1.2-mL bolus of BR1. Ultrasonographic images of liver and right kidney and of spleen and left kidney were obtained intermittently for 5 minutes with low-mechanical-index software (to minimize microbubble destruction) that shows stationary microbubbles in green. Percentage total uptake was calculated as the number of green pixels in the region of interest for each organ over time, divided by the total pixels. Relative uptake, the ratio of total uptake in liver to that in right kidney and of total uptake in spleen to that in left kidney, and differential uptake, the difference in total uptake between liver and right kidney and between spleen and left kidney, were calculated. Total uptake for each organ was plotted against time, and the gradient of a best-fit straight line was calculated. Wilcoxon signed rank test was used to compare mean uptake values in each subject. Mann-Whitney U test was used for comparisons in sex and age. RESULTS: Total uptake declined over 5 minutes in left and right kidney and in liver (from 88% +/- 10% [1 minute] to 67% +/- 14% [5 minutes]), but not in spleen (range, 90%-99%). Mean relative uptake +/- 1 SD for spleen increased from 2.3 +/- 0.7 (1 minute) to 3.7 +/- 2.3 (5 minutes) (P =.005) but for liver was constant: 2.1 +/- 0.9 (1 minute) and 2.3 +/- 0.4 (5 minutes) (P =.06). Mean differential uptake +/- 1 SD for spleen increased from 51.3% +/- 14.9% (1 minute) to 65.0% +/- 9.1% (5 minutes) (P =.002). Significant difference was seen over time in total uptake gradients between spleen and left kidney (P =.014) but not between liver and right kidney or right and left kidney. No difference was seen between men and women or with age. CONCLUSION: BR1 produces spleen-specific enhancement that is longer (5 minutes) than the blood pool phase.

Adult↗

PubMed2005

Microbubble production in an in vitro cardiopulmonary bypass circuit ventilated with xenon.

Xenon, as an anaesthetic gas, has the potential to be used in an increasing range of applications. However, its use in cardiopulmonary bypass (CPB) has not yet progressed from the rat model due to concerns that its relative insolubility may cause microbubble formation and/or expansion in the micro-vasculature of the patient. An in vitro CPB circuit was designed to create and measure gaseous microbubbles over a range of temperature gradients, pressure drop and gas tensions. We were able to demonstrate that our test circuit did not produce any significant microbubbles and that, under normal physiological blood pressures, a fixed gas bubble in connection with the circuit did not grow in the presence of Xe.

Blood Gas Analysis↗

PubMed2005

Clinical use of renal perfusion imaging by means of harmonic sonography with a microbubble contrast agent in patients after renal transplantation: preliminary study.

OBJECTIVE: The purpose of this research was to determine the feasibility of renal perfusion imaging by means of harmonic sonography with a microbubble contrast agent for the evaluation of renal perfusion after renal transplantation compared with technetium Tc 99m diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) scans. METHODS: During a 10-month period, 100 patients with renal transplantation that included normal perfusion (n=68) and delayed perfusion including chronic rejection (n=19), acute rejection (n=9), arterial stenosis (n=2), and urinary stricture (n=2) underwent sonographic renal perfusion imaging and (99m)Tc-DTPA scans. Sonographic images were obtained every 3 seconds for a total of 3 minutes after administration of a bolus injection of 4 g of the microbubble contrast agent at a concentration of 300 mg/mL. Sonographic renal perfusion images were converted into a renal perfusion curve, and the calculated time at the peak of the curve (T(peak)) was compared with that of the (99m)Tc-DTPA scan. RESULTS: The T(peak) with the (99m)Tc-DTPA scan was 14.9 seconds in the normal group and 33 seconds in the delayed perfusion group. The T(peak) on sonographic renal perfusion images was 25 seconds in the normal group and 44.8 seconds in the delayed perfusion group. Sonographic renal perfusion images showed good correlation with the (99m)Tc-DTPA scan (r=0.74; P=.0001). The cutoff value of the T(peak) on sonographic renal perfusion images was 35 seconds (sensitivity=85%; specificity=90%). CONCLUSIONS: The renal perfusion images obtained by means of harmonic sonography with a microbubble contrast agent constitute an effective sonographic technique for the evaluation of renal perfusion abnormalities after renal transplantation compared with a (99m)Tc-DTPA scan.

Adult↗

PubMed2005

Incidence of cardiac arrhythmias with therapeutic versus diagnostic ultrasound and intravenous microbubbles.

OBJECTIVE: The purpose of this study was to determine the type of arrhythmias induced with therapeutic versus diagnostic transthoracic low-frequency ultrasound (TLFUS) transducers in the presence of intravenous microbubbles. METHODS: Intravenous perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles were infused or given as a bolus injection while TLFUS was applied in the standard parasternal and apical views with either a 1-MHz therapeutic ultrasound transducer or high-mechanical-index diagnostic ultrasound (1.7 MHz). RESULTS: Significantly more ectopy was produced by the therapeutic transducer, especially at higher-intensity settings in the continuous wave mode after bolus injections of PESDA (P < .001 compared with lower intensities and lower continuous infusion rates). Six patients (15%) had either clinical supraventricular tachycardia or nonsustained ventricular tachycardia after intravenous PESDA with therapeutic TLFUS. In comparison, diagnostic high-mechanical-index ultrasound produced only isolated ventricular ectopy and no sustained ventricular arrhythmias. CONCLUSIONS: Intravenously injected microbubbles and low-frequency therapeutic transducers operating at longer duty cycles and wide beam widths have the capability of eliciting clinically important arrhythmias in patients at high risk for such events.

Adult↗

PubMed2005

Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine.

Endothelial cells (EC) of angiogenic tumor vasculature are characterized by altered expression of molecular markers on their surface. Numerous peptides have been identified that specifically bind tumor angiogenic endothelium, including the tripeptide arginine-arginine-leucine (RRL). We hypothesized that ultrasound contrast microbubbles (MB) targeted via linkage with RRL would specifically adhere to tumor angiogenic endothelium versus normal myocardium, and that this selective adhesion could be detected ultrasonically. Microbubbles were conjugated to cyclic peptides containing either RRL (RRL-MB) or a glycine control sequence (control-MB). As measured in a parallel plate flow chamber, in vitro adhesion of RRL-MBs was three times greater to cultured tumor-derived ECs than to normal ECs (P < 0.01), demonstrating selective binding of RRL-MBs to tumor endothelium. Mice bearing s.c. Clone C or PC3 tumors were given i.v. injections of fluorescent RRL to show in vivo localization to tumor vasculature or were ultrasonically imaged following i.v. injections of targeted contrast MBs. Ultrasound images showed strong RRL-MB contrast enhancement within the tumors but not the control tissue myocardium. Control-MBs caused minimal enhancement in either tissue. Quantitative acoustic videointensity was significantly greater for the tumors than the hearts (5 +/- 1 versus 0.5 +/- 1 intensity units; P = 0.001). These data show that ultrasound contrast MBs targeted to tumor vasculature via RRL preferentially adhere to tumor versus normal vasculature and that this selective adherence can be detected with ultrasound. Targeted microbubbles may thus offer a noninvasive contrast-enhanced ultrasound imaging technique for the functional imaging of tumor neovascularization, and may have further implications for therapeutic tumor targeting.

Animals↗

PubMed2005

Enhanced sonography using carbon dioxide gas for small hepatocellular carcinoma: a comparison study between pure carbon dioxide gas and carbon dioxide microbubbles.

PURPOSE: To evaluate the feasibility of enhanced sonography using arterial injection of pure carbon dioxide gas (CO(2)) for detecting small hepatocellular carcinoma (HCC) nodules. MATERIALS AND METHODS: We performed enhanced sonography on 51 HCC nodules of 35 patients with HCC. The patients underwent enhanced sonography with two methods: injection of pure CO(2) (26 nodules), or injection of CO(2) microbubbles (25 nodules) using CO(2) and soy bean oil. We observed the enhancement effect of HCC on enhanced sonography, and measured the accumulation time of CO(2) in the nodules. RESULTS: Twenty-three nodules appeared hyperechoic on enhanced sonography, and 12 of the nodules could be found on enhanced sonography only. Sixteen of the hyperechoic nodules on baseline sonography revealed no enhancement. Multiple regression analysis with regard to the method of injection of CO(2), nodule location, and nodule size revealed that method (p<0.0001) and nodule size (p=0.02) remained significant. The accumulation time of CO(2) microbubbles in the nodules was 4.4+/-0.8 minutes, whereas pure CO(2) accumulation time was 14.7+/-1.5 minutes, significantly longer than the CO(2) microbubbles regardless of nodule size and location. CONCLUSION: Enhanced sonography of arterial injection of pure CO(2) is a feasible technique for detecting small HCC nodules.

Adult↗

PubMed2006

Microbubble contrast for radiological imaging: 1. Principles.

Microbubble contrast for ultrasound imaging in radiology has finally come of age, adding entirely new capabilities to real time imaging. Following a bolus injection into a peripheral vein of as little as 0.1mL of an aqueous suspension, contrast specific imaging modes show parenchymal and lesional perfusion in real time in the major organs of the abdomen and pelvis as well as breast, thyroid and prostate. These new imaging modes exploit the unique interaction between ultrasound and microbubbles, which gives rise to nonlinear echoes that are readily distinguishable from those of tissue. Furthermore, microbubbles can be deliberately disrupted by the ultrasound imaging field. The rate at which fresh bubbles then replenish the scanplane can be metered in subsequent images, offering a means to quantify both flowrate and relative vascular volume of the microvasculature in both organs and solid lesions.

Contrast Media↗

PubMed2006

[Reversion of multidrug resistance of hepatocellular carcinoma by antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation].

OBJECTIVE: To study whether antisense oligonucleotides and ultrasonic microbubble intensifier transfection combined with ultrasound irradiation is an effective and directional way in reversing multidrug resistance (MDR) in tumors. METHODS: Mdr1, mrp, and lrp genes antisense oligonucleotides on the ultrasound microbubble intensifier were transfected for the human HepG2/ADM cell lines and then the cells were radiated with low intensity ultrasound. The effects of the reversion of carcinoma cells' MDR and the reduction of their malignancy and growth capability in vitro and in vivo were assessed using RT-PCR, Western blot and MTT. RESULTS: The treatment restrained the multiplication of the human HepG2/AMD cell lines. The levels of their mRNA and protein of cells' mdr1 and mrp genes dropped significantly. Growth of the subcutaneous transplanted tumors in the nude mice decreased. CONCLUSIONS: Transfection of MDR genes antisense oligonucleotides on the ultrasonic microbubble intensifier combined with low intensity ultrasound radiation may serve as a new treatment method for hepatocellular carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

[Preparation and evaluation of microbubble ultrasound contrast agent with N-carboxymethyl chitosan].

OBJECTIVE: To prepare microbubble, made of N-carboxymethyl chitosan, as ultrasound contrast agent and evaluate its characteristics and acoustic effects in vivo. METHODS: Oil-Water-Oil multiple emulsion/solvent evaporation method was used to prepare the microbubble contrast agent. Both optical micrography and scanning electron micrography were performed to determine the bubble size and morphology. The acoustic effect of the N-carboxymethyl chitosan echo contrast agent was evaluated in vivo in rabbit. Liver echo images were recorded with ultrasound machine before and after intravenous bolus injecting 0.5 ml of the agent. RESULTS: The novel N-carboxymethyl chitosan echo contrast agent was formulated as lyophilized product, with a mean diameter of 2-3 microm and a shell thickness of 250-300 nm. Its size is relatively uniform. The imaging effect was remarkably enhanced with the ultrasonic contrast agent when applied in rabbit livers. CONCLUSION: It is feasible to prepare excellent microbubble ultrasound contrast agent with N-carboxymethyl chitosan as membrane components.

Animals↗

PubMed1982

Microbubble formation: in vitro and in vivo observation.

Injection of liquid through a catheter into the circulation is known to produce clouds of signals detected by sonography. Blood forced through a stenotic conduit produced sonographic clouding, and bubbles of 10-100 microns were observed were observed by light microscopy. The microbubbles persisted up to three and a half minutes. Microbubbles were observed in the microcirculation of the rat by placing the catheter tip into the descending aorta of 15 animals, viewing the mesentery at 400X magnification, and recording the results on videotape. Following injection of the rats' own blood, numerous microbubbles lodged promptly at the arteriolar level and obstructed blood flow for up to 200 sec before shrinking sufficiently to pass downstream and allow restitution of flow.

Animals↗

PubMed2000

Inhibitory effect of meconium on pulmonary surfactant function tested in vitro using the stable microbubble test.

UNLABELLED: Meconium aspiration syndrome is related to mechanical obstruction of the airways and subsequent chemical pneumonitis. It has also been suggested that meconium causes inhibition of surfactant function. To assess its inhibitory effect on surfactant function in vitro, we used a stable microbubble (SM) test that was thought to reflect the adequacy of pulmonary surfactant. The mixtures were prepared by adding serial dilutions of human meconium to various concentrations of Surfactant-TA (Surfacten). The SM count at each concentration of surfactant significantly increased with the increasing concentration of surfactant. This shows that the SM test closely reflects the quantified function of surfactant. When various concentrations of meconium were added to the surfactant concentration of 0.05 mg/ml and 0.25 mg/ml, the SM test results were decreased even at low concentrations of meconium. Also the increase in the meconium concentration caused a decrease in the SM test result, which was dependent on the surfactant and the meconium concentration, accordingly. These results suggest that meconium inhibits surfactant function. CONCLUSION: The stable microbubble test is an effective indirect method that tests the changes in surfactant quantity. In the in vitro experiment, we observed an inhibitory effect of meconium on the surfactant activity using the stable microbubble test.

Biological Products↗