Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Microbubbles”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2004

The use of microbubbles to target drug delivery.

Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed.

Drug Delivery Systems↗
PubMed2006

Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: We compared measurements of tumor perfusion from microbubble contrast-enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an animal tumor model. METHODS: Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 microL of a perfluoropropane microbubble contrast agent (Definity; Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high-mechanical index pulse was delivered to destroy the microbubbles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T(10) map and 35 serial T(1)-weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; alpha, 30 degrees ) after the injection of 100 microL of 0.2-mmol/kg gadopentetate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel analyses of both data sets were performed; microbubble contrast-enhanced sonography returned estimates of microvessel cross-sectional area, microbubble velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion-permeability index and the extravascular extracellular volume fraction. RESULTS: Comparing similar regions of tumor tissue seen on sonography and MRI, region-of-interest analyses revealed a strong (r(2) = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities. CONCLUSIONS: Microbubble contrast-enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel analysis is performed, and this analysis correlates with similar DCE-MRI measurements.

Animals↗
PubMed2001

Effect of pressure on intracardiac backscatter from microbubbles.

The backscatter from sonicated albumin microbubbles (Albunex) was analyzed using acoustic densitometry in an in vitro pulsatile heart model to evaluate the effects of pressure on the backscatter from Albunex, and the cardiac cyclic changes of intracardiac backscatter from sonicated albumin microbubbles in 16 healthy persons were analyzed. It was found that the Albunex microbubbles were compressed in systole and decompressed in diastole, causing corresponding changes of backscatter in cardiac cycle. Although the intensities of backscatter in diastole and systole were related to the concentration of microbubbles, the concentration of microbubbles had no effect on the difference of end-diastolic and end-systolic backscatter. The difference of the backscatter was highly correlated with end-systolic pressure (r = 0.96, P = 0.001). In human studies, we also observed same intracardiac cyclic changes of backscatter from sonicated albumin microbubbles. Our study indicates that it is possible to evaluate the intracardiac pressure non-invasively by analyzing the intracardiac backscatter from the microbubbles with acoustic densitometry.

Acoustics↗
PubMed1995

Ultrasound and microbubbles: their generation, detection and potential utilization in tissue and organ therapy--experimental.

Ultrasound-induced cavitation in tissue and organs has been well recognized and documented. Generally, this phenomenon has been seen as something to be avoided except in cases such as lithotripsy, where its production is considered an essential part of the treatment process or as a desirable contrast media in some areas of visualization enhancement. This article covers three areas in which the phenomenon has been observed, and shows how the effect can or may be therapeutically beneficial. Studies in the pig show that implanted human gallstones and the gallbladder itself can be eliminated in a nonsurgical procedure using ultrasound-induced cavitation in the gallbladder. In the dog brain, relatively stable cavitation-induced microbubbles have been transported through the vascular system to regions outside a focal seeding site. These bubbles produce ablation of tissue volumes at a remote site when irradiated with appropriate ultrasound. The cavitation phenomenon has been observed in the dog and human prostate. In the human prostate, microbubbles transported from ultrasound-induced focal seeding sites can be readily visualized with ultrasound and may be potentially useful under controlled conditions in tissue debulking for the treatment of benign prostatic hyperplasia (BPH). A similar microbubble transport has not been seen in the dog prostate under similar ultrasound treatment parameters. The ability to detect cavitation-induced microbubbles, follow their transportation through the vascular system and excite them at the appropriate time and place provides interesting possibilities for therapy. Of course, the entire microbubble process can be avoided by working below the cavitation threshold, thereby using only the absorption of ultrasound in tissue to produce focal thermal lesions. The term microbubble is used here in the context of those bubbles which can be transported in the vascular system down to vessels diameters below the 100-microns range. This is the vessel size in the vascular field into which microbubbles are transported and can be both visualized as well as disrupted with ultrasound.

Absorption↗
PubMed2004

Radionuclide tumour therapy with ultrasound contrast microbubbles.

Radionuclides have shown to be effective in tumour therapy. However, the side effects determine the maximum deliverable dose. Recently, it has been demonstrated that cells can be permeabilised through sonoporation using ultrasound and contrast microbubbles. The use of sonoporation in treatment of tumours may increase the anti-tumour efficacy of radionuclide treatment. The mechanisms as well as the effects sonoporation in tumour treatment strategies are still not understood. The purpose of this study is to determine the effects of ultrasound and contrast microbubbles on the internalisation of the radionuclide (111)In-DOTA-Tyr(3)-octreotate in tumour cells. To optimize ultrasound settings for ultrasound adjunctive tumour therapy we incubated rat pancreatic CA20948 tumour cells with two dyes (MW 40 and 70 kDa). The uptake levels were compared with cells treated with ultrasound and contrast microbubbles for different ultrasound settings. The highest molecular uptake was found with addition of contrast microbubbles (ratio of 10 bubbles to 1 cell) and with the ultrasound setting: duty cycle 0.013%, mechanical index (MI) 0.42, and treatment times of 30 and 60 min. These settings were used to enhance the internalisation of (111)In-DOTA-Tyr(3)-octreotate. We found a 160% higher internalisation of (111)In-DOTA-Tyr(3)-octreotate by tumour cells adjunctively treated with ultrasound and contrast microbubbles compared to untreated cells. These results show that adjunctive tumour treatment with the radionuclide (111)In-DOTA-Tyr(3)-octreotate and ultrasound contrast microbubbles may be feasible. When using adjunctive ultrasound contrast microbubble treatment, a lower radionuclide doses are required to reach the same anti-tumour effect.

Animals↗
PubMed2002

DNA-loaded albumin microbubbles enhance ultrasound-mediated transfection in vitro.

Ultrasound (US), with or without microbubbles, enhances gene transfer in cultured cells, but the effect is modest. We tested if attaching DNA to albumin microbubbles during bubble synthesis could enhance gene expression. Plasmid DNA was loaded on the albumin shell over a range of concentrations (500 to 10,000 microg/mL). Optimal gene expression occurred with loading doses of 4000 microg DNA/mL (4k-loaded bubbles). These microbubbles had diameters of 2.4 +/- 0.7 microm and carried 40 pg DNA/microbubble. DNA-loaded microbubbles had optimal transfection at higher delivered doses of DNA than unloaded bubbles mixed with plasmid. The 4k-loaded bubbles demonstrated a fivefold (p = 0.0003) increase in luciferase reporter expression over that with unloaded bubbles. Similarly, transfection efficiency was better for 4k-loaded microbubbles than unloaded microbubbles (41 +/- 3% vs. 9 +/- 3%, p < 0.0001). DNA loading of microbubbles enhances gene expression and transfection efficiency in US-targeted transfection in vitro and may represent an improved avenue for therapeutic gene delivery in vivo.

Albumins↗
PubMed2002

Influence of injection site, microvascular pressure and ultrasound variables on microbubble-mediated delivery of microspheres to muscle.

OBJECTIVES: Our objective was to test the hypothesis that the ultrasound pulsing interval (PI), microbubble injection site and microvascular pressure significantly influence the transport of 100-nm microspheres to muscle through extravasation sites created by the destruction of microbubbles with ultrasound. BACKGROUND: Microbubbles show promise as targeted drug and gene delivery agents; however, designing optimal microbubble-based therapies will require an understanding of the factors that influence the transport of microbubble-delivered, gene-bearing vehicles to tissue. METHODS: Ultrasound at 1 MHz, with a peak negative pressure amplitude of 0.75 MPa, was applied to microbubbles and 100-nm microspheres in exteriorized rat spinotrapezius muscle. Ultrasound PIs of 1, 3, 5 and 10 s, arterial microsphere injection times of 10 or 40 s and arterial versus venous injection sites were tested. RESULTS: Extravasation point creation and microsphere delivery were greatest when the ultrasound PI was 5 or 10 s. No significant differences in extravasation point creation or microsphere delivery were observed with arterial versus venous microbubble injection, but a trend toward increased microsphere delivery with arterial injection may exist. Decreasing the arterial injection time from 40 to 10 s increased microvascular pressure, which, in turn, substantially enhanced microsphere transport to tissue, without a concomitant increase in the number of extravasation points. CONCLUSIONS: The ultrasound PI and microvascular pressure significantly influence the creation of extravasation points and the transport of microspheres to tissue. These factors may be important in designing and optimizing contrast ultrasound-based therapies.

Animals↗
PubMed1997

Albumin microbubble adherence to human coronary endothelium: implications for assessment of endothelial function using myocardial contrast echocardiography.

OBJECTIVES: We hypothesized that sonicated 5% human albumin microbubbles (Albunex) adhere to disrupted vascular endothelium and that this interaction is a marker of endothelial integrity. This study sought to identify sites and determinants of Albunex-endothelial cell (EC) attachment. BACKGROUND: Under normal conditions, Albunex microbubbles used in myocardial contrast echocardiography (MCE) pass unimpeded through the coronary microcirculation. During pathophysiologic states associated with endothelial dysfunction, however, microbubbles linger in the myocardium despite normal flow. The sites and conditions regulating microbubble adhesion are unknown. METHODS: Coverslips with cultured human coronary artery ECs were mounted in a parallel plate perfusion system and perfused with a suspension of fluorescein-labeled Albunex in culture medium, followed by a bubble-free wash at a wall shear rate of 100 s-1. To create inflammatory ECs, phorbol myristate acetate was added 4.5 h before perfusion, and flow cytometry was used to confirm an inflammatory response. Perfusions were performed under normal and inflammatory conditions using surfaces of confluent and subconfluent ECs and isolated extracellular matrix. Bubble adherence was quantified in 20 random fields per cover-slip using epifluorescent video microscopy. RESULTS: No microbubbles adhered to normal confluent ECs, although small numbers adhered to inflamed ECs (0.03 +/- 0.01 bubbles/cell, p < 0.01 vs. normal cells). Fever microbubbles attached to normal versus inflamed matrix of both partially exposed (1,800 +/- 520 vs. 4,100 +/- 1,000 bubbles/mm2, p = 0.05) and completely denuded (2,700 +/- 1,300 vs. 7,200 +/- 1,100 bubbles/ mm2, p < 0.03) endothelium. CONCLUSIONS: Albunex microbubbles preferentially adhere to inflammatory endothelial extracellular matrix. These data suggest that MCE can be used to noninvasively study endothelial integrity and may have implications for the assessment of preclinical atherosclerotic heart disease.

Adhesiveness↗
PubMedDate not supplied

Increased ultrasound contrast and decreased microbubble destruction rates with triggered ultrasound imaging.

Although transient myocardial contrast imaging has been able to produce visually evident myocardial contrast in animals and humans with very low intravenous doses of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles, the mechanism for improved contrast remains unclear. In this study we devised a flow chamber that measured the concentration of PESDA microbubbles that remained after exposure to diagnostic ultrasound pressures of 0.9 to 1.9 MPa and frequencies of 2.0, 2.5, and 3.5 MHz (first and second harmonic for 2.0 MHz), which were delivered at either 30 Hz (frames per second), 0.5 to 1.0 Hz, or without any ultrasound transmission. The videointensity within the flow chamber was also measured at 0, 20, 40, and 100 ml/min flow rates with the flow loop closed (i.e., constant microbubble concentration) with both triggered (0.5 to 1.0 Hz) and conventional (30 Hz) frame rates. The effluent microbubble concentration was significantly larger when PESDA was exposed to either no ultrasound or 0.5 to 1.0 Hz ultrasound. Furthermore, the videointensity of a constant number of microbubbles was significantly greater with 0.5 to 1.0 Hz (triggered) compared with 30 Hz (conventional) frame rates at each transmit frequency. The greatest difference was noted with the lower 2.0 MHz transmit frequency and the 20 ml/min flow rate, especially when a second harmonic receiving frequency was used. We conclude that the mechanism for improved contrast with triggered ultrasound imaging is because of both less microbubble destruction and increased videointensity from a constant number of microbubbles. Lower transducer frequencies and lower flow rates result in the greatest improvement in videointensity with triggered ultrasound transmission.

Albumins↗
PubMedDate not supplied

The effect of ultrasound frame rate on perfluorocarbon-exposed sonicated dextrose albumin microbubble size and concentration when insonifying at different flow rates, transducer frequencies, and acoustic outputs.

The purpose of this article was to compare the effects of 1 and 30 Hz frame rates on perfluorocarbon-exposed sonicated dextrose albumin microbubble size and concentration in a flow cell containing either saline or blood at 37 degrees C. Microbubble size and concentration of perfluorocarbon-exposed sonicated dextrose albumin were measured after insonation at different acoustic outputs, transducer frequencies, and flow rates with the use of the two different frame rates and compared with no ultrasound exposure. At 2.0 MHz insonation frequency, microbubble concentration was significantly reduced with the use of a 30 Hz frame rate and peak negative pressures of 1.1 megaPascal (mPa). This destruction did not occur when using a lower acoustic output, a 1 Hz frame rate, or when flow rate was increased to 100 cc/min. One-hertz frame rates at 2.0 MHz resulted in a significantly larger mean microbubble size than 30 Hz or no ultrasound in both saline and blood, which was in part due to selective destruction of smaller microbubbles. These findings indicate that 30 Hz frame rates destroy perfluorocarbon-exposed sonicated dextrose albumin microbubbles only at higher diagnostic acoustic outputs. A 1 Hz frame rate prevents this destruction, especially destruction of larger (> 5.0 microns) microbubbles.

Acoustics↗
PubMed1999

Microbubbles and mitral valve prostheses - transesophageal echocardiographic evaluation.

OBJECTIVE: To assess whether microbubbles are associated with a specific type of mitral valve prosthesis and to investigate the relationship of microbubbles to ventricular function and mitral regurgitation. One of the types of spontaneous echocardiographic contrast observed in patients with prosthetic heart valves has been described as microbubbles. METHODS: Clinical data and videotapes of patients with a prosthetic mitral valve who had undergone transesophageal echocardiography at the UCLA Medical Center between May 1989 and February 1995 were retrospectively reviewed. There were 109 studies (74 patients) available for review by two independent observers. RESULTS: Microbubbles occurred in 49 of the 66 studies of St. Jude valves ( 74%), eight of the 12 studies of Bjork Shiley valves (67%), four of four studies of Medtronic valves (100%) and zero of 23 studies of tissue valves (0%). Patients with an estimated ejection fraction greater than 45% were found to have a much higher likelihood of having microbubbles observed. There was no statistically significant association between the degree of mitral regurgitation and the observation of microbubbles. CONCLUSIONS: Microbubbles are a common phenomenon occurring in patients with mechanical mitral prostheses compared with tissue mitral valve prostheses. Their formation depends on the systolic ventricular function, suggesting a cavitation-like phenomenon participating in their formation perhaps due to the rate or velocity of the valve closure.

Adolescent↗
PubMedDate not supplied

Local drug and gene delivery through microbubbles.

Ultrasound contrast agents (microbubbles) lower the threshold for cavitation by ultrasound energy. Ultrasound microbubbles may be used as cavitation nuclei for drug and gene delivery. By tailoring the physical properties of microbubbles and coating materials, drugs and genetic drugs can be incorporated into ultrasound contrast agents. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing the therapeutic agents. Cavitation also causes a local shockwave that improves cellular uptake of the therapeutic agent. As a result of the human genome project and continuing advances in molecular biology, many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Transthoracic ultrasound can be focused on the heart so that an intravenous injection of gene-bearing microbubbles will deliver genes relatively selectively to the myocardium. Using this technique, we have produced high levels of transgene expression in the insonated region of the myocardium. This new technology, using microbubbles and ultrasound for drug and gene delivery, merits further study and development.

Animals↗
PubMed2003

Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins.

BACKGROUND: Noninvasive methods for characterizing neovessel formation during angiogenesis are currently lacking. We hypothesized that angiogenesis could be imaged with the use of contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins. METHODS AND RESULTS: Microbubbles targeted to alpha(v)-integrins were prepared by conjugating echistatin (MB(E)) or monoclonal antibody against murine alpha(v) (MB(alpha)) to their surface. Control microbubbles (MB(c)) were also prepared. The microvascular behavior of these microbubbles was assessed by intravital microscopy of the cremaster muscle in mice treated for 4 days with sustained-release FGF-2. Microvascular retention was much greater (P<0.01) for MB(E) (11+/-6 mm(-3)) and MB(alpha) (10+/-7 mm(-3)) than that for MB(c) (1+/-1 mm(-3)). Retained MB(E) and MB(alpha) attached directly to the microvascular endothelial surface. Microbubble retention in 4 control mice was minimal. Subcutaneous matrigel plugs enriched with FGF-2 were created in 12 mice and studied 10 days later. Neovessels within the matrigel stained positive for alpha(v)-integrins. CEU demonstrated greater (P<0.01) acoustic intensity for MB(E) (16.0+/-5.9 U) and MB(alpha) (17.0+/-5.5 U) compared with MB(c) (5.8+/-2.6 U). The signal from targeted microbubbles (MB(E) and MB(alpha)) correlated well (r=0.90) with the matrigel blood volume determined by CEU perfusion imaging. CONCLUSIONS: CEU with microbubbles targeted for alpha(v)-integrins may provide a noninvasive method for assessing therapeutic angiogenesis.

Animals↗
PubMed2000

Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium.

BACKGROUND: The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hypothesis that albumin-coated microbubbles could be used to effectively deliver an adenoviral transgene to rat myocardium by ultrasound-mediated microbubble destruction. METHODS AND RESULTS: Recombinant adenovirus containing beta-galactosidase and driven by a constitutive promoter was attached to the surface of albumin-coated, perfluoropropane-filled microbubbles. These bubbles were infused into the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contain virus, virus alone, and virus plus ultrasound. One group underwent ultrasound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for beta-galactosidase expression. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside substrate, indicating expression of the transgene. None of the control animals showed myocardial expression of the beta-galactosidase transgene. By quantitative analysis, beta-galactosidase activity was 10-fold higher in the treated group than in controls (P<0.0001). CONCLUSIONS: Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.

Albumins↗
PubMed1998

Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion.

BACKGROUND: Ultrasound can cause microbubble destruction. If microbubbles are administered as a continuous infusion, then their destruction within the myocardium and measurement of their myocardial reappearance rate at steady state will provide a measure of mean myocardial microbubble velocity. Conversely, measurement of their myocardial concentration at steady state will provide an assessment of microvascular cross-sectional area. Myocardial blood flow (MBF) can then be calculated from the product of the two. METHODS AND RESULTS: Ex vivo and in vitro experiments were performed in which either flow was held constant and pulsing interval (interval between microbubble destruction and replenishment) was altered, or vice versa. In vivo experiments were performed in 21 dogs. In group 1 dogs (n=7), MBF was mechanically altered in a model in which coronary blood volume was constant. In group 2 dogs (n=5), MBF was altered by direct coronary infusions of vasodilators. In group 3 dogs (n=9), non-flow-limiting coronary stenoses were created, and MBF was measured before and after the venous administration of a coronary vasodilator. In all experiments, microbubbles were delivered as a constant infusion, and myocardial contrast echocardiography was performed using different pulsing intervals. The myocardial video intensity versus pulsing interval plots were fitted to an exponential function: y=A(1-e[-betat]), where A is the plateau video intensity reflecting the microvascular cross-sectional area, and beta reflects the rate of rise of video intensity and, hence, microbubble velocity. Excellent correlations were found between flow and beta, as well as flow and the product of A and beta. CONCLUSIONS: MBF can be quantified with myocardial contrast echocardiography during a venous infusion of microbubbles. This novel approach has potential for measuring tissue perfusion in any organ accessible to ultrasound.

Animals↗
PubMed1998

Albumin microbubble persistence during myocardial contrast echocardiography is associated with microvascular endothelial glycocalyx damage.

BACKGROUND: We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury. METHODS AND RESULTS: The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K+ content, pH, PO2, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP. CONCLUSIONS: Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.

Animals↗
PubMed1989

The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography.

The purpose of this study was to determine whether the behavior of sonicated albumin microbubbles accurately mimics red blood cell flow in the microcirculation and is thus consistent with their use as in vivo tracers of red blood cell flow during myocardial contrast echocardiography. Accordingly, microbubbles prepared from fluorescein-conjugated albumin and fluorescently labeled red blood cells were injected intravascularly in eight golden hamsters. Their intravascular distribution, velocities, arteriolar-to-venular transit and flux ratios at branch points were determined in the microcirculation of the cheek pouch. Albumin microbubbles (mean diameter, 4.9 +/- 3.6 microns) and red blood cells displayed a similar frequency of distribution across the arteriolar lumen (33% in the central 20% of the arterioles), and their arteriolar velocities were also similar (2.5 +/- 0.7 mm/sec and 2.3 +/- 0.7 mm/sec,p = NS). The mean velocities of microbubbles correlated well with those of red blood cells at baseline and after adenosine application (r = 0.97 and r = 0.89, respectively), as did the calculated maximum velocity (r = 0.98 and r = 0.80, baseline and adenosine, respectively). The velocity profiles across the lumen of the vessels for albumin microbubbles and red blood cells were similar at baseline and after adenosine-induced velocity changes. The flux ratios at branch points also correlated well (r = 0.92, p less than 0.001). Arteriolar-to-venular transit times of albumin microbubbles were similar to those of red blood cells in vessels ranging in size from 22 microns to 45 microns. We conclude that the behavior of albumin microbubbles in the microcirculation mimics that of red blood cells and supports their use as intravascular tracers of red blood cell flow during myocardial contrast echocardiography.

Animals↗
PubMed2001

Usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax.

OBJECTIVE: The suspended microbubble sign is defined as the image seen on ultrasonography consisting of a pleural effusion strewn with numerous hyperechoic pinpoints and more or less linear shadows that move synchronously with respiration. In this study, we intended to evaluate the clinical usefulness of the suspended microbubble sign in differentiating empyemic and nonempyemic hydropneumothorax. METHODS: This series consisted of 8 patients with empyemic hydropneumothorax and 23 patients with nonempyemic hydropneumothorax. The finding of the presence of the suspended microbubble signs on ultrasonography was recorded. To further elucidate the generation of the suspended microbubble sign, the interaction between air and pleural fluid of different types was investigated in vitro. RESULTS: The suspended microbubble sign was shown on ultrasonography in all 8 patients with empyemic hydropneumothorax but was absent in the 23 patients with nonempyemic hydropneumothorax. These findings were supported by the observation that the pus seemed to mix with and trap the air more easily than did the nonpurulent pleural fluid, as shown in vitro. In this selected population, the sensitivity and specificity of the suspended microbubble sign in aiding a diagnosis of empyemic hydropneumothorax were both 100%. CONCLUSION: The suspended microbubble sign shown on ultrasonography might be of considerable value in differentiating empyemic and nonempyemic hydropneumothorax.

Diagnosis, Differential↗