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At least 289 records · Page 16Linked to original sources

PubMed1992

Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent.

We have previously reported that ultrastable lipid-coated microbubbles make a suitable ultrasonic contrast agent in the brain, causing increased intensity of echoes that persists for many hours. We showed that intravenously administered lipid-coated microbubbles accumulate selectively in rat brain gliomas with echogenicity enhancement for up to 1 hour, allowing visualization of the growing lesions 40% (2 days) earlier than can be seen without contrast. This work is a detailed evaluation of the accumulation of the lipid-coated microbubbles in tumor and the effect of the bubbles on the echogenicity of insonified tumors. Using a lipid-specific stain, we measured and characterized the distribution of the bubbles in the brain and tumor. We showed that on the scan, the enhancement of the tumor is accompanied by a change in the signal-to-noise ratio of the echoes from the tumor. We identified characteristic textural changes associated with contrast-enhanced tumor using spectral analysis.

Animals↗

PubMed2003

Microbubble-augmented ultrasound declotting of thrombosed arteriovenous dialysis grafts in dogs.

PURPOSE: Transcutaneous low-frequency ultrasound (LFUS) can effectively lyse clots in the presence of microbubbles. This study was designed to test the commercially available human albumin microspheres injectable suspension octafluoropropane formulation, Optison, to establish efficacy and assess US parameters of intensity and wave modes in a canine model of a thrombosed arteriovenous (dialysis) graft. MATERIALS AND METHODS: Arteriovenous grafts in five dogs were cannulated, temporarily ligated, and thrombosed. Different declotting techniques were randomized to treat nine groups. Control groups involved direct saline (4.5 mL) clot injection in 0.5-1.0-mL increments. One group underwent peripheral intravenous microbubble injection (13.5 mL). Six groups underwent direct incremental clot injection of 4.5 mL of microspheres with LFUS for 30 minutes in 3-5-minute increments with use of various intensity settings in continuous-wave and pulsed-wave (PW) modes. At each increment, angiography was used to grade flow, declotting, and overall success. RESULTS: One hundred four procedures showed success in all 24 high-intensity PW modes (1.2-2.0 W/cm(2)); only one of 20 control experiments was successful (P <.0001). Medium-intensity modes yielded intermediate success rates. Lowest-intensity direct-injection groups and intravenous and control groups ranked lower. Results at 30 minutes were better than at 15 minutes (P <.0001). CONCLUSIONS: LFUS with direct injection of microbubbles is effective in lysing moderate-sized clots and recanalizing thrombosed arteriovenous grafts. It best succeeds at the higher range of intensity settings tested in PW mode. Further development is justified.

Albumins↗

PubMed1979

Maturity of fetal lungs tested by production of stable microbubbles in amniotic fluid.

Lung surfactant in amniotic fluid, and hence the maturity of the fetal lungs, can be assessed by observation of stable microbubbles (less than 15 micron diameter). Bubbles are formed by agitation with a Pasteur pipette and examined in hanging drops under the 10 x power of a microscope. Either after a count of bubbles, or after a general survey of hanging drops, the fluid is given a stable microbubble rating. A 'strong' rating indicates that the idiopathic respiratory distress syndrome will not occur after delivery, and that the lecithin/sphingomyelin ratio will indicate maturity. Complete absence of stable microbubbles suggests a high risk of respiratory trouble for the newborn infant, as does a weak or lower rating in the 30 to 37 week gestational age group. The test takes 5 to 10 minutes to perform, is cheap and easy, is not affected by blood, but may be affected by meconium. If a 'strong' rating is found, measurement of the L/S ratio can safely be omitted.

Amniotic Fluid↗

PubMed1999

Interaction of Microbubbles with Ultrasound.

The clinical need for bedside myocardial perfusion studies is obvious in the present era of revascularization. Animal and first clinical studies suggest that microbubbles can be used as intravascular tracers of perfusion in conjunction with echocardiography as an imaging modality. In order to fully appreciate the potential and limitations of this approach, the complex interactions of microbubbles within an acoustic field need to be elucidated. Most importantly, there is a strong dependence of bubble effects on the acoustic pressure. At low pressures, linear backscatter yields low signal intensities; at medium range of pressures, bubble resonance causes the reflection of nonlinear signals with harmonic frequencies; and at high pressures, spontaneous acoustic emission with high signal intensity occurs as a final signal of the bubble in its process of disintegration. Thus, in order to allow sufficient replenishment of bubbles to the imaging plane, triggered imaging should be used with one frame every second to eighth cardiac cycle. Traditional gray scale echocardiography was not successful as an imaging modality because of the similarity of gray shades between the myocardium and the contrast effect. Subsequently, second harmonic imaging was developed and was fairly successful in contrast detection, although inherent problems persisted due to the overlap of fundamental and harmonic frequencies in the filtered signals. Harmonic power Doppler imaging turned out as the most sensitive acquisition method, however, with an early dropout at medium range attenuation. In theory, the new technique of pulse inversion may be most promising as this bubble specific imaging modality should combine high sensitivity of detection with great tolerance for attenuation effects in humans. First in vitro studies have confirmed its superiority over harmonic power Doppler in combination with stabilized microbubbles such as SonoVuetrade mark. Thus, we will have to accomplish a lot more work and comparative studies in humans before myocardial contrast echocardiography can emerge as a reproducible technique for evaluating myocardial perfusion with high diagnostic accuracy.

Journal Article↗

PubMed2002

High heat flux cooling by microbubble emission boiling.

In subcooled flow boiling of water in a horizontal rectangular channel, microbubble emission boiling occurred at higher subcooling of liquid in transition boiling, and the heat flux increased more than the critical heat flux. The maximum heat flux reached 10 MW/m(2) for a channel with 12 mm x 14mm cross-section at 40K liquid subcooling and 0.5 m/sec liquid velocity. For smaller rectangular channels with 14 mm x 5mm, 14mm x 3mm, and 14mm x 1mm cross-sections, the maximum heat flux was 7 MW/m(2)-more than 20 times the cooling limit of a present day CPU. Microbubble emission boiling is expected to realize high heat flux cooling for electronic devices. In convection boiling with subcooled water jet, the same boiling regime and heat flux were obtained for a downward heating surface and an upward heating surface. In subcooled flow boiling with strong convection, the hydrodynamic force is predominant for vapor-liquid exchange. Accordingly, microbubble emission boiling is expected for high heat flux cooling or high heat flux heat transfer in microgravity.

Journal Article↗

PubMed2003

The ultrasonic weak short-pulse responses of microbubbles based on a two-frequency approximation.

The ultrasonic short-pulse responses of microbubbles are of interest in cavitation, transient responses, and contrast imaging. We extend the two-frequency analytic solutions of Newhouse and Shankar [J. Acoust. Soc. Am. 75, 1473-1477 (1984)] to approximate the short-pulse responses of microbubbles in a low-amplitude field. Based on their results, there is an expected component near dc in the spectrum of bubble echoes excited by a short pulse. Here this component is named the low-frequency response, and its theoretical properties are verified experimentally. Including the fundamental and second-harmonic components, the weak short-pulse responses of microbubbles include three types of response. Our work has determined the constraint conditions under which this approximated solution can be used to analyze these short-pulse responses. This paper also provides the amplitude and spectral properties of these responses. The low-frequency response has a special bandwidth-dependent property and has potential applications in imaging and bubble sizing.

Journal Article↗

PubMed1996

Effect of static pressure on acoustic transmittance of Albunex microbubble suspensions.

Albunex (ALX), an albumin-stabilized microbubble echo contrast agent, is sensitive to pressures similar to those produced by the heart. The tested hypothesis was that the acoustic transmittance of ALX suspensions will increase with increasing hydrostatic pressure (Ps). The test involved an acoustic setup analogous to a spectrophotometer. The acoustic transmittance of microbubble suspensions was strongly Ps dependent. Transmittance at 1 MHz was essentially zero at ambient pressure, increasing to approximately 50%, approximately 63%, and nearly 100% at Ps of 80, 120, and 400 mm Hg, respectively. The ultrasound pulses used to interrogate samples were without measurable effect on the acoustic transmittance of suspensions maintained at ambient pressure during experimental measurements. The data indicate that many of the microbubbles are destroyed at Ps comparable to those produced by the heart.

Acoustics↗

PubMed1999

Shock wave-inertial microbubble interaction: methodology, physical characterization, and bioeffect study.

A method of generating in situ shock wave-inertial microbubble interaction by a modified electrohydraulic shock wave lithotripter is proposed and tested in vitro. An annular brass ellipsoidal reflector (thickness = 28 mm) that can be mounted on the aperture rim of a Dornier XL-1 lithotripter was designed and fabricated. This ring reflector shares the same foci with the XL-1 reflector, but is 15 mm short in major axis. Thus, a small portion of the spherical shock wave, generated by a spark discharge at the first focus (F1) of the reflector, is reflected and diffracted by the ring reflector, producing a weak shock wave approximately 8.5 microseconds in front of the lithotripter pulse. Based on the configuration of the ring reflector (different combinations of six identical segments), the peak negative pressure of the preceding weak shock wave at the second focus (F2) can be adjusted from -0.96 to -1.91 MPa, at an output voltage of 25 kV. The preceding shock wave induces inertial microbubbles, most of which expand to a maximum size of 100-200 microns, with a few expanding up to 400 microns before being collapsed in situ by the ensuing lithotripter pulse. Physical characterizations utilizing polyvinylidene difluoride (PVDF) membrane hydrophone, high-speed shadowgraph imaging, and passive cavitation detection have shown strong secondary shock wave emission immediately following the propagating lithotripter shock front, and microjet formation along the wave propagation direction. Using the modified reflector, injury to mouse lymphoid cells is significantly increased at high exposure (up to 50% with shock number > 100). With optimal pulse combination, the maximum efficiency of shock wave-induced membrane permeabilization can be enhanced substantially (up to 91%), achieved at a low exposure of 50 shocks. These results suggest that shock wave-inertial microbubble interaction may be used selectively to either enhance the efficiency of shock wave-mediated macromolecule delivery at low exposure or tissue destruction at high exposure.

Acoustics↗

PubMed2002

Mechanism of parenchymal enhancement of the liver with a microbubble-based US contrast medium: an intravital microscopy study in rats.

PURPOSE: To investigate the mechanism of prolonged contrast material enhancement of the liver observed with the lipid-shell ultrasonographic (US) contrast agent AF0150, with use of intravital microscopy. MATERIALS AND METHODS: Eight Sprague-Dawley rats were used. Six received fluorescent microspheres to label the Kupffer cells; two were used as controls. The edge of the middle lobe of the liver was transilluminated with white light. Fluorescent microspheres were observed under fluorescence light. After injection of AF0150, behavior of microbubbles was observed for 6 minutes while viewing a single high-power field. Multiple other fields were then assessed for stationary bubbles and their relation to Kupffer cells. The number of bubbles in motion, aggregated, stationary, and associated with labeled cells were counted. RESULTS: Of 590 bubbles, 34 (5.8%) became stationary and 556 (94.2%) kept moving. Of the 34 stationary microbubbles, 21 dislodged within 30 seconds. Microbubbles were homogeneously distributed throughout the lobule, in contrast to the dominant periportal distribution of the labeled Kupffer cells. Among 83 stationary bubbles observed from all fields of view, only 14 (17%) were associated with fluorescent-labeled cells. CONCLUSION: The late parenchymal liver enhancement effect of AF0150 is likely not related to Kupffer-cell uptake, but rather to a mechanical slowdown within the sinusoids.

Animals↗

PubMed2000

Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis.

PURPOSE: To characterize blood flow in focal hepatic lesions with harmonic ultrasonographic (US) imaging and a microbubble contrast agent. MATERIALS AND METHODS: Thirty patients with known hepatic masses were examined after injection of a perfluorocarbon microbubble agent. Tumor vascularity was assessed with continuous, harmonic gray-scale imaging with a low mechanical index (MI). Tumor vascular volume was assessed with brief, high-MI insonation called interval-delay imaging, which caused microbubble destruction. As the total contrast agent volume in the liver reflects the total vascular volume, quantitation of lesion enhancement relative to normal hepatic enhancement helped determine the vascular volume of the tumor relative to that of normal parenchyma. RESULTS: Low-MI continuous harmonic imaging showed lesional vessels in hepatocellular carcinomas, minimal or no vessels in hemangiomas, and variable vascularization in metastases. High-MI interval-delay imaging showed greater enhancement in hepatocellular carcinomas than in normal liver (P <.02) and showed less enhancement in hemangiomas than in normal liver (P <.02). Enhancement in metastases was greater in the margins than in the center; as a result, the lesions appeared smaller (P <.03) and less well defined on the interval-delay images. CONCLUSION: Contrast-enhanced harmonic imaging appears superior to conventional Doppler US for hepatic mass characterization. Low-MI continuous and high-MI interval-delay imaging can help assess tumor vascular pattern and microvascular volume.

Adult↗

PubMed2000

Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: usefulness of power Doppler US with a microbubble contrast agent in evaluating therapeutic response-preliminary results.

PURPOSE: To evaluate the usefulness of power Doppler ultrasonography (US) with a microbubble contrast agent in assessing the therapeutic response of hepatocellular carcinomas (HCCs) treated with percutaneous radio-frequency (RF) ablation. MATERIALS AND METHODS: Forty patients with 45 nodular HCC lesions 1.0-3.8 cm in diameter underwent power Doppler US before and after intravenous injection of a microbubble contrast agent. The same procedures were repeated after US-guided percutaneous RF ablation. The results of these studies were compared with those of three-phase helical computed tomography (CT) performed immediately after RF ablation. RESULTS: Before RF ablation, nonenhanced power Doppler US demonstrated flow signals within tumor in 33 of 45 HCCs. After contrast agent administration, flow signals increased or newly appeared in all cases. After RF ablation, none of the ablated tumors showed intratumoral flow signals at nonenhanced power Doppler US, whereas six showed marginal intratumoral flow signals at contrast agent-enhanced power Doppler US. These six tumors were found to have small enhancing foci, suggestive of viable tumor, in corresponding areas at immediate follow-up CT. Additional RF ablation or transcatheter arterial chemoembolization was performed in these tumors. CONCLUSION: The results of power Doppler US with a microbubble contrast agent in HCCs treated with RF ablation correlated well with those of contrast-enhanced CT. Preliminary data suggest that contrast-enhanced power Doppler US can be a promising noninvasive technique for assessing therapeutic response.

Adult↗

PubMed1979

The lung as a filter for microbubbles.

A new ultrasonic Doppler device has been used noninvasively over the femoral artery of anesthetized dogs to prove that it can detect carefully calibrated microbubbles of 14--189 micrometers diam when these are infused directly into the aorta. The same evaluated technique has then been employed to detect any bubbles escaping into the arterial system when gas was infused into the venous system either as microbubbles or as a bolus. Results from 18 dogs showed that, under normal conditions, the lungs are a superb filter for bubbles and that any cutoff diameter is less than 22 micrometers. However, bubbles escaped entrapment when the lungs were severely overloaded with gas (20 ml) or were pretreated with a pulmonary vasodilator (aminophylline). The dog preparation and arterial Doppler device appear to be ideal for future studies to determine what other factors might compromise the capability of the lungs to filter microbubbles. Physiological parameters showed dramatic changes when bubbles were detected as escaping into the arterial system by comparison with their effect when retained within the lungs. Changes in respiration profile indicated that they may offer a useful index of the degree of venous embolization and, hence, a warning of impending overload leading to arterial embolization.

Air↗

PubMed1998

The stable microbubble test on tracheal aspirate samples from newborn babies for diagnosis of surfactant deficiency and/or surfactant malfunction.

For predicting the risk of respiratory distress syndrome (RDS), lung surfactant in amniotic fluid can be assessed by observation of stable microbubbles (< 15 microns diameter). It was investigated if the stable microbubble test (MT) developed on amniotic fluid could be applied on tracheal aspirate samples (TA) obtained from newborn infants. Forty-four TA from 29 newborn infants without pulmonary diseases (group 1) and 65 TA from 21 newborn infants with respiratory insufficiency (group 2) were analyzed by the MT for predicting surfactant deficiency and/or surfactant malfunction. Ten microbubbles/ mm2 was defined as cutoff value of the MT. A specificity of 90% and a sensitivity of 52% was obtained with this cutoff value. A much lower rate of false negative results (sensitivity 91%) was noted after surface tension measurement of TA. The sensitivity of the MT (52%) does not encourage the use of the MT on TA.

Cohort Studies↗

PubMed2003

Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart.

BACKGROUND: Noninvasive, tissue-specific delivery of therapeutic agents would be a valuable clinical tool. We have previously shown that ultrasound-targeted microbubble destruction can direct expression of an adenoviral reporter to the heart. The present study shows that this method can be applied to selectively deliver plasmid vectors to the heart. METHODS AND RESULTS: We used albumin and lipid microbubbles containing plasmids with a luciferase transgene to target the heart in rats. After 4 days, organs were harvested and analyzed for reporter gene expression. In a second set of experiments, the hearts of rats treated with plasmids were harvested at various time points during a 4-week period. Both luciferase activity and mRNA concentrations were measured. Luciferase transfection with plasmids showed highly specific gene expression in the heart, with hardly any activity in control organs. Time course evaluation showed high transgene expression in the first 4 days, with a rapid decline thereafter. Repeated treatment produced a second peak of transgene expression with similar decay. CONCLUSIONS: Ultrasound-mediated destruction of microbubbles directs plasmid transgene expression to the heart with much greater specificity than viral vectors and can be regulated by repeated treatments. This noninvasive technique is a promising method for cardiac gene therapy.

Animals↗

PubMed1998

Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells.

BACKGROUND: Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1). METHODS AND RESULTS: A perfluorobutane gas-filled lipid-derived microsphere with monoclonal antibody to ICAM-1 covalently bound to the bubble shell was synthesized. Bubbles with either nonspecific IgG or no protein on the shell were synthesized as controls. Coverslips of cultured human coronary artery ECs were placed in a parallel-plate perfusion chamber and exposed to 1 of the 3 microbubble species, followed by perfusion with culture medium. Experiments were performed with either normal or interleukin-1beta-activated ECs overexpressing ICAM-1, and bubble adherence was quantified with epifluorescent videomicroscopy. There was limited adherence of control bubbles to normal or activated ECs, whereas a 40-fold increase in adhesion occurred when anti-ICAM-1-conjugated bubbles were exposed to activated ECs compared with normal ECs (8.1+/-3.5 versus 0.21+/-0.09 bubbles per cell, respectively, P<0.001). Although diminished, this difference persisted even after perfusion at higher wall shear rates. CONCLUSIONS: A gas-filled microbubble with anti-ICAM-1 antibody on its shell specifically binds to activated ECs overexpressing ICAM-1. Diagnostic ultrasound in conjunction with targeted contrast agents has the unique potential to characterize cell phenotype in vivo.

Antibodies, Monoclonal↗

PubMed1998

Delivery of colloidal particles and red blood cells to tissue through microvessel ruptures created by targeted microbubble destruction with ultrasound.

BACKGROUND: We have previously shown that the application of ultrasound to thin-shelled microbubbles flowing through small microvessels (<7 microm in diameter) produces vessel wall ruptures in vivo. Because many intravascular drug- and gene-delivery vehicles are limited by the endothelial barrier, we hypothesized that this phenomenon could be used to deliver drug-bearing vehicles to tissue. METHODS AND RESULTS: An exteriorized rat spinotrapezius muscle preparation was used. Intravascular fluorescent red blood cells and polymer microspheres (PM) (205 and 503 nm in diameter) were delivered to the interstitium of rat skeletal muscle through microvessel ruptures created by insonifying microbubbles in vivo. On intravital microscopy, mean dispersion areas per rupture for red blood cells, 503-nm PM, and 205-nm PM were 14.5x10(3) microm2, 24. 2x10(3) microm2, and 27.2x10(3) microm2, respectively. PM dispersion areas were significantly larger than the mean dispersion area for red blood cells (P<0.05). CONCLUSIONS: Microvessel ruptures caused by insonification of microbubbles in vivo may provide a minimally invasive means for delivering colloidal particles and engineered red blood cells across the endothelial lining of a targeted tissue region.

Animals↗

PubMed1998

Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue.

BACKGROUND: Our aim was to observe ultrasound-induced intravascular microbubble destruction in vivo and to characterize any resultant bioeffects. METHODS AND RESULTS: Intravital microscopy was used to visualize the spinotrapezius muscle in 15 rats during ultrasound delivery. Microbubble destruction during ultrasound exposure caused rupture of < or = 7-microm microvessels (mostly capillaries) and the production of nonviable cells in adjacent tissue. The number of microvessels ruptured and cells damaged correlated linearly (P<0.001) with the amount of ultrasound energy delivered. CONCLUSIONS: Microbubbles can be destroyed by ultrasound, resulting in a bioeffect that could be used for local drug delivery, angiogenesis, and vascular remodeling, or for tumor destruction.

Air↗

PubMed1999

Subharmonic imaging with microbubble contrast agents: initial results.

The subharmonic emission from insonified contrast microbubbles was used to create a new imaging modality called Subharmonic Imaging. The subharmonic response of contrast microbubbles to ultrasound pulses was first investigated for determining adequate acoustic transmit parameters. Subharmonic A-lines and gray scale images were then obtained using a laboratory pulse-echo system in vitro and a modified ultrasound scanner in vivo. Excellent suppression of all backscattered signals other than from contrast microbubbles was achieved for subharmonic A-lines in vitro while further optimization is required for in vivo gray scale subharmonic images.

Animals↗