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.

SourceResearch connectionFrom yearThrough year

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

At least 145 records · Page 8Linked to original sources

PubMed2005

In vivo acceleration of ultrasonic tissue heating by microbubble agent.

The ultrasonic power absorbed by a microbubble in its continuous wave response is estimated through numerically solving a version of the Rayleigh-Plesset equation. At an ultrasonic frequency of 3 MHz, a resonant microbubble, approximately 1.1 microm in radius, showed an absorption cross section of about 0.005 mm2 in its low power response. This estimation predicts that the tissue ultrasonic absorption will be doubled when such microbubbles are delivered to the tissue at a concentration of about eight bubbles/mm3 in tissue. An exteriorized murine kidney was exposed to focused ultrasound at 3.2 MHz in degassed saline, and the tissue temperature change was measured. With an intravenous bolus administration of a microbubble agent, the ultrasonically induced temperature elevation was multiplied by up to five times. The enhancement in temperature elevation gradually decreased as the microbubble agent was eliminated from the body. The experimental results agreed with the prediction in the order of magnitude. This effect may have a potential use to enhance the throughput as well as the selectivity of focused ultrasound treatment.

Albumins↗

PubMed2005

Influence of lipid shell physicochemical properties on ultrasound-induced microbubble destruction.

We present the first study of the effects of monolayer shell physicochemical properties on the destruction of lipid-coated microbubbles during insonification with single, one-cycle pulses at 2.25 MHz and low-duty cycles. Shell cohesiveness was changed by varying phospholipid and emulsifier composition, and shell microstructure was controlled by postproduction processing. Individual microbubbles with initial resting diameters between 1 and 10 microm were isolated and recorded during pulsing with bright-field and fluorescence video microscopy. Microbubble destruction occurred through two modes: acoustic dissolution at 400 and 600 kPa and fragmentation at 800 kPa peak negative pressure. Lipid composition significantly impacted the acoustic dissolution rate, fragmentation propensity, and mechanism of excess lipid shedding. Less cohesive shells resulted in micron-scale or smaller particles of excess lipid material that shed either spontaneously or on the next pulse. Conversely, more cohesive shells resulted in the buildup of shell-associated lipid strands and globular aggregates of several microns in size; the latter showed a significant increase in total shell surface area and lability. Lipid-coated microbubbles were observed to reach a stable size over many pulses at intermediate acoustic pressures. Observations of shell microstructure between pulses allowed interpretation of the state of the shell during oscillation. We briefly discuss the implications of these results for therapeutic and diagnostic applications involving lipid-coated microbubbles as ultrasound contrast agents and drug/gene delivery vehicles.

Coated Materials, Biocompatible↗

PubMed2005

High-speed photography during ultrasound illustrates potential therapeutic applications of microbubbles.

Ultrasound contrast agents consist of microscopically small encapsulated bubbles that oscillate upon insonification. To enhance diagnostic ultrasound imaging techniques and to explore therapeutic applications, these medical microbubbles have been studied with the aid of high-speed photography. We filmed medical microbubbles at higher frame rates than the ultrasonic frequency transmitted. Microbubbles with thin lipid shells have been observed to act as microsyringes during one single ultrasonic cycle. This jetting phenomenon presumably causes sonoporation. Furthermore, we observed that the gas content can be forced out of albumin-encapsulated microbubbles. These free bubbles have been observed to jet, too. It is concluded that microbubbles might act as a vehicle to carry a drug in gas phase to a region of interest, where it has to be released by diagnostic ultrasound. This opens up a whole new area of potential applications of diagnostic ultrasound related to targeted imaging and therapeutic delivery of drugs such as nitric oxide.

Biophysical Phenomena↗

PubMed2004

Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction.

We showed previously that microbubble destruction with pulsed 1-MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded but the medial feed artery was left intact. Control muscles were similarly occluded but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow and number of smooth muscle (SM) alpha-actin-positive vessels, >30-mum arterioles, and capillaries per fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble-treated muscles, lateral region hyperemia blood flow was increased at all time points and restored to normal at day 28. The number of SM alpha-actin vessels per fiber was increased over control in this region at days 7 and 14 but decreased by day 28, when larger-diameter arterioles became more prevalent in the medial region. The number of capillaries per fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.

Animals↗

PubMed2004

Ultrasound microbubble destruction imaging in acute middle cerebral artery stroke.

BACKGROUND AND PURPOSE: Cerebral perfusion imaging in acute stroke assists in determining the subtype and the severity of ischemia. Recent studies in perfusion models and in healthy volunteers have shown that ultrasound perfusion imaging based on microbubble destruction can be used to assess tissue perfusion. We applied ultrasound microbubble destruction imaging (MDI) to identify perfusion deficits in patients with acute middle cerebral artery (MCA) territory stroke. METHODS: Fifteen acute MCA stroke patients with sufficient transtemporal bone windows were investigated with ultrasound MDI and perfusion-weighted MRI (PWI). MDI was performed using power pulse-inversion contrast harmonic imaging. Thirty seconds after a bolus injection of the echo contrast agent SonoVue, microbubbles were destroyed using a series of high-energy pulses. Local perfusion status was analyzed in selected regions of interest by destruction curves and acoustic intensity differences (DeltaI) before and after microbubble destruction. Local perfusion status was then compared with perfusion compromise as identified on PWI. RESULTS: The mean differences of acoustic intensity from the ischemic MCA territory were significantly diminished compared with the normal hemisphere (DeltaI=2.52+/-1.75 versus DeltaI=13.79+/-7.31; P<0.001), resulting in lower slopes of microbubble destruction. PWI confirmed perfusion changes in the selected anatomical regions on time-to-peak maps in all 15 patients. CONCLUSIONS: MDI is a qualitative method that can rapidly detect perfusion changes in acute stroke. When combined with other ultrasound techniques and PWI, it may well be valuable in the care of stroke unit patients, eg, as a screening method and for follow-up assessments of perfusion deficits.

Adult↗

PubMed2006

Air microbubbles as MR susceptibility contrast agent at 1.5 Tesla.

Air microbubbles have been investigated recently at high magnetic field strength (2 Tesla or greater) as potential MR susceptibility contrast agents. We used a phantom to measure their susceptibility at 1.5 T to clarify their usefulness for this purpose. The phantom, filled with fresh Levovist suspension at 4 different doses (67 to 125 mg/mL), was continuously scanned with a gradient-echo technique at a temporal resolution of 10 s. The transverse relaxation increase (R2*) by microbubbles demonstrated a time course of exponential decay at each dose (time-constant, 39 to 57 s). The dependency of R2* on microbubble volume fraction was linear, with a slope of 89 s-1 per percentage microbubble volume fraction. Our study represents the first step towards applying microbubbles as susceptibility contrast agents at 1.5 T.

Air↗

PubMed2006

Microvascular behavior and effects of sonazoid microbubbles in the cremaster muscle of rats after local administration.

OBJECTIVE: The purpose of this study was to observe Sonazoid perfluorobutane microbubbles (GE Healthcare, Amersham, Buckinghamshire, England) in and their effects on the cremaster capillary microcirculation of rats. METHODS: Sonazoid (0.3 x 10(9) microbubbles in 0.5 mL) was observed by intravital microscopy in the cremaster muscle after retrograde administration into the femoral artery of 6 animals. Microbubble and microvessel diameters and blood flow velocities and the overall mean and SD of the 1-minute volume flow through the microscopic field were calculated from the 2 to 4 capillaries observed in the field of each animal. Fluorescein isothiocyanate-dextran leakage was used to assess extravasation after microbubble passage. RESULTS: seconds, respectively, before they were released and capillary flow normalized. No microbubble size changes, damming, or coalescence of bubbles and no changes in microvessel diameter or microvascular blood flow velocities, volume flow, or perfusion heterogeneity occurred during or after the passage of the Sonazoid suspension or the vehicle. No fluorescein isothiocyanate-dextran leakage was observed. CONCLUSIONS: The passage of Sonazoid bubbles at concentrations higher than those expected after intravenous administration of the Sonazoid did not durably impair microvascular perfusion, structural integrity, or macromolecular retention in the rat cremaster muscle. The duration of discrete capillary obstructions was short and in all cases comparable with that of naturally occurring leukocyte plugging.

Animals↗

PubMed1986

Production of microbubbles for use as echo contrast agents.

A variety of agents have been proposed for use as contrast for ultrasound studies. Several reports suggest the use of microbubbles because of their superior sonographic resolution. We describe a method of producing calibrated microbubbles utilizing differential absorption and gas injection techniques. Gas injection methods are described using a Plexiglas microbubbler apparatus with a fine needle orifice. The bubbles originally produced by this device are in a size range of 40-100 microns and consist of nitrogen (10%) and carbon dioxide (90%). The differential absorption technique uses THAM [tris(hydroxymethyl)aminomethane hydrochloride] to absorb the carbon dioxide (diluent gas) from the bubbles selectively, leaving smaller microbubbles. The microbubbles can be calibrated using the electric gating principle of the Coulter Counter.

Bicarbonates↗

PubMed2004

In vivo study of microbubbles as an MR susceptibility contrast agent.

The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison, was studied with rat liver imaging at 7 T. Optison suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (deltaR2*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro deltaR2* measurements of Optison suspension at different concentrations are also reported.

Albumins↗

PubMed1981

Range gated Doppler ultrasound detection of contrast echographic microbubbles for cardiac and great vessel blood flow patterns.

Ultrasonic contrast techniques allow tracking of blood flow in patients with cardiac malformations. One problem often encountered in M-mode contrast is inability to generate adequate microbubbles for recording. Theoretically, echo Doppler should be more sensitive for detection of microbubbles. To test this hypothesis, results of 75 saline injections were studied at catheterization in 16 patients by simultaneously recording contrast M-mode and echo Doppler studies. For this part of the investigation, an ATL 500 system was utilized. The M-mode of this system was found to provide identical information to that of SmithKline. Records were evaluated without identification of the patient. In all instances (n = 20) in which microbubbles were not expected on the basis of flow patterns, none were detected by Doppler. One error occurred for M-mode. Contrast in the direction of flow was visualized in 50 of 55 injections by echo Doppler. In these, a frequency dispersion was present, but even more striking was a marked rise in the time interval histographic input signal strength indicator. Only 40 of 55 simultaneous M-mode echoes showed a contrast effect (p less than 0.05). Doppler microbubble detection was usually represented by a much stronger signal than was M-mode contrast. This investigation demonstrates that range gated Doppler is an effective method for microbubble detection.

Child↗

PubMed2006

Ultrasound-targeted microbubble destruction improves the low density lipoprotein receptor gene expression in HepG2 cells.

Ultrasound-targeted microbubble destruction had been employed in gene delivery and promised great potential. Liver has unique features that make it attractive for gene therapy. However, it poses formidable obstacles to hepatocyte-specific gene delivery. This study was designed to test the efficiency of therapeutic gene transfer and expression mediated by ultrasound/microbubble strategy in HepG2 cell line. Air-filled albumin microbubbles were prepared and mixed with plasmid DNA encoding low density lipoprotein receptor (LDLR) and green fluorescent protein. The mixture of the DNA and microbubbles was administer to cultured HepG2 cells under variable ultrasound conditions. Transfection rate of the transferred gene and cell viability were assessed by FACS analysis, confocal laser scanning microscopy, Western blot analysis and Trypan blue staining. The result demonstrated that microbubbles with ultrasound irradiation can significantly elevate exogenous LDLR gene expression and the expressed LDLRs were functional and active to uptake their ligands. We conclude that ultrasound-targeted microbubble destruction has the potential to promote safe and efficient LDLR gene transfer into hepatocytes. With further refinement, it may represent an effective nonviral avenue of gene therapy for liver-involved genetic diseases.

Cell Line, Tumor↗

PubMed2006

Ultrasound contrast agent, Levovist microbubbles are phagocytosed by Kupffer cells-In vitro and in vivo studies.

Phase contrast microscopy showed that Levovist microbubbles were phagocytosed by cultured Kupffer cells and moved gradually toward the nucleus from the cell surface. They were diminished in size and disappeared within 30min by diffusion of the gas contained within the microbubbles. In an in vivo study, confocal laser scanning microscopy demonstrated that Levovist microbubbles were trapped and phagocytosed by Kupffer cells. No microbubbles were observed attached to the sinusoidal endothelium. Our findings suggest that liver-specific images obtained following intravenous injection of Levovist are composed of signals from microbubbles phagocytosed by Kupffer cells.

Journal Article↗

PubMed1996

Thrombolytic enhancement with perfluorocarbon-exposed sonicated dextrose albumin microbubbles.

Whereas low-intensity, high-frequency ultrasound (US) alone appears to cause minimal thrombolysis, US combined with air-filled microbubbles does increase the amount of urokinase (UK)-mediated clot lysis (CL). Because this phenomenon may be mediated by cavitation-induced streaming, we hypothesized that perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles, which are more stable than air-filled microbubbles, may also enhance US-induced thrombolysis. We measured the percentage CL of equally sized thrombi (1.0 +/- 0.1 mg) made from freshly drawn blood incubated for 2 hours and then exposed to 20 kHz US (0.846 MPa peak negative pressure). The thrombi were bathed in 4 ml of saline solution, UK alone (20,000 U), PESDA alone, or a combination of PESDA with UK. The percentage CL achieved with PESDA and therapeutic US was also compared with the percentage CL achieved with room air-filled sonicated dextrose albumin (RASDA) microbubbles. When compared with US alone (24% +/- 13% CL) or UK alone (17% +/- 3% CL), PESDA plus US produced significantly better CL (43% +/- 17%; p< 0.05). PESDA combined with US also produced significantly greater CL than RASDA combined with US (28% +/- 9%; p < 0.05). The optimal CL was achieved with a combination of PESDA with UK with US (60% +/- 14% CL). We conclude that PESDA microbubbles alone may be capable of inducing thrombolysis when insonified with a low-frequency transducer.

Contrast Media↗

PubMed1997

Deoxygenated blood minimizes adherence of sonicated albumin microbubbles during cardioplegic arrest and after blood reperfusion: experimental and clinical observations with myocardial contrast echocardiography.

Both administration of cardioplegic solution and blood reperfusion result in endothelial dysfunction. The transit rate of albumin microbubbles during myocardial contrast echocardiography may reflect endothelial injury. Accordingly, we performed myocardial contrast echocardiography in 12 dogs undergoing cardiopulmonary bypass and measured the myocardial transit rate of microbubbles injected into the aortic root during delivery of cardioplegic solutions containing arterial and venous blood and delivery of pure crystalloid cardioplegic solution. The myocardial transit rate of 99mTc-labeled red blood cells was measured and perfusates were sampled for biochemical analysis at each stage. The microbubble transit rate was markedly prolonged during delivery of crystalloid cardioplegic solution and improved significantly during infusion of blood cardioplegic solution (p < 0.001); venous compared with arterial blood in the solution resulted in a greater rate (p < 0.001). The microbubble transit rate did not correlate with pH, oxygen tension or carbon dioxide tension values, or K+ concentration. The red blood cell transit rate remained constant regardless of the cardioplegic perfusate infused. Myocardial contrast echocardiography was also performed in 12 patients undergoing coronary artery bypass who underwent sequential arterial and venous reperfusion after cardioplegic arrest. The microbubble transit rate was faster with venous than arterial blood reperfusion (p = 0.01), although this gain was diminished when arterial blood reperfusion preceded venous blood reperfusion (p = 0.05). Our results indicate that endothelial dysfunction after cardioplegic arrest may be ameliorated by reperfusion with venous rather than arterial blood.

Albumins↗

PubMed2000

Quantification of microbubble destruction of three fluorocarbon-filled ultrasonic contrast agents.

The assessment of myocardial blood velocity using ultrasonic contrast agents is based on the premise that the vast majority of contrast microbubbles within a myocardial region can be destroyed by an acoustic pulse of sufficient magnitude. Determination of the period of time after destruction that a region of myocardium needs to reperfuse may be used to assess myocardial blood velocity. In this study, we investigated the acoustic pressure sensitivity of three solutions of intravenous fluorocarbon-filled contrast agents and the magnitude of acoustic pulse required to destroy the contrast agent microbubbles. A novel tissue-mimicking phantom was designed and manufactured to investigate the relationships between mean integrated backscatter, incident acoustic pressure and number of frames of insonation for three fluorocarbon-filled contrast agents (Definity(R), Optison(R), and Sonazoid(R), formerly NC100100). Using a routine clinical ultrasound (US) scanner (Acuson XP-10), modified to allow access to the unprocessed US data, the contrast agents were scanned at the four acoustic output powers. All three agents initially demonstrated a linear relationship between mean integrated backscatter and number of frames of insonation. For all three agents, mean integrated backscatter decreased more rapidly at higher acoustic pressures, suggesting a more rapid destruction of the microbubbles. In spite of the fact that there was no movement of microbubbles into or out of the beam, only the results from Definity(R) suggested that a complete destruction of the contrast agent microbubbles had occurred within the total duration of insonation in this study.

Albumins↗

PubMedDate not supplied

Microbubbles induce renal hemorrhage when exposed to diagnostic ultrasound in anesthetized rats.

The generation of ultrasound (US) bioeffects using a clinical imaging system is controversial. We tested the hypothesis that the presence of microbubbles in the US field of a medical imager induces biologic effects. Both kidneys of anesthetized rats were insonified for 5 min using a medical imaging system after the administration of microbubbles. One kidney was insonified using a continuous mode (30 Hz) and the opposite kidney was insonified using an intermittent (1 Hz) technique. The microbubbles were exposed to three different transducer frequencies and four transducer output powers. After insonification, the animals were euthanized, the kidneys were removed and their gross appearance scored under "blinded" conditions using a defined scale. After the administration of microbubbles, US imaging of the kidney caused hemorrhage in the renal tissue. The severity and area of hemorrhage increased with an increase in the transducer power and a decrease in the transducer frequency. Intermittent insonification in the presence of microbubbles produced a greater degree of renal hemorrhage than continuous imaging techniques.

Animals↗

PubMed1999

In vivo kinetics of microbubbles of SH U 508 A (Levovist): comparison with indocyanine green in rabbits.

The aim of this study was to evaluate in vivo kinetics of microbubbles of SH U 508 A, in comparison with Indocyanine Green, a dye used as an indicator of blood flow. Microbubble kinetics were evaluated in various vessels (i.e., vena cava, aorta, renal artery, renal vein and portal vein) in rabbits after injection of SH U 508 A by measuring Doppler signals (n = 5). The kinetics of Indocyanine Green were evaluated by measuring absorbance using a photodiode (n = 5). Test substances (SH U 508 A 300 mg/mL and Indocyanine Green 1.25 mg/mL) were injected IV at a dose of 0.1 mL/kg B.W. Peak signal intensity was observed immediately after injection of SH U 508 A, followed by biphasic decay. The rates of biphasic decay were similar in all vessels. A second peak of the signal, which indicated recirculation of the microbubbles, was observed in the vena cava. The circulation and recirculation times of the microbubbles after injection of SH U 508 A were similar to that of Indocyanine Green. These findings suggest that the majority of SH U 508 A microbubbles circulate through the body similarly to blood flow, without retention, in the vasculature.

Animals↗

PubMed2003

Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction.

OBJECTIVES: This study was undertaken to optimize echocardiographic parameters for successful gene delivery to the heart and to extend the method from adenoviral to plasmid deoxyribonucleic acid (DNA). BACKGROUND: We have previously shown that ultrasound-targeted microbubble destruction can direct tissue expression of adenoviral transgenes to the heart. The optimal echocardiographic parameters for this technique have not been reported. METHODS: Adenoviral or plasmid DNA encoding the luciferase reporter gene was incorporated into liposome microbubbles and infused intravenously into anesthetized rats. We systematically evaluated the effects of ultrasound parameters known to influence microbubble destruction, including electrocardiogram (ECG) triggering, ultrasound frequency, mode of ultrasound, and mechanical index, on gene expression in rat myocardium four days after treatment. In addition, gene expression in heart, liver, and skeletal muscle were compared between adenoviral and plasmid DNA. RESULTS: Optimal ultrasound parameters for this technique include low-transmission frequency (1.3 MHz), maximal mechanical index, and ECG triggering to allow complete filling of the myocardial capillary bed by microbubbles. No difference was seen between ultraharmonics and power Doppler mode. Using adenoviral DNA, optimal ultrasound parameters yielded myocardial luciferase activity on the order of 104 relative light units/mg protein/min but with even higher liver activity. Plasmid DNA was expressed in rat myocardium at similar levels but without detectable liver expression. CONCLUSIONS: Ultrasound-targeted microbubble destruction can be used to deliver adenoviral or plasmid DNA to the myocardium. This technique holds great promise in applying the rapidly expanding repertoire of gene therapies being developed for cardiac disease.

Adenoviridae↗