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At least 199 records · Page 11Linked to original sources

PubMed1986

Effects of platelet antagonists on the reduction in platelet density caused by microbubbles in vitro.

Platelet-rich plasma (PRP) was stirred and incubated at 37 degrees C with N2 microbubbles in vitro in the presence and absence of platelet antagonists. The N2 microbubbles acted as a platelet agonist, like "classical" agonists such as ADP, collagen, and thrombin, causing an agonist-induced aggregation requiring extracellular Ca2+. This aggregation is abolished by 2-ethylamineglycolether (N',N',N',N') tetraacetate (chelator of extracellular Ca2+), and 2-deoxy-D-glucose plus antimycin A (inhibitors of glycolysis and electron transport, and thereby of ATP production). Furthermore, this aggregation could be depressed pharmacologically by several antagonists of the aggregation induced by "classical" platelet agonists. The greatest inhibition of microbubble-induced aggregation was obtained by substances that increase the intracellular levels of cyclic AMP. Medications that are in common clinical use, such as theophylline, seem promising in this respect. The prostaglandin-thromboxane pathway did not seem to be involved in the N2 microbubble-induced platelet aggregation in vitro, since acetylsalicylic acid and indomethacin were without effect, nor did the 3',5'-cyclic guanosine monophosphate pathway seem to be linked to this aggregation mechanism.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1988

[A newly developed instrument of microbubble test for evaluation of fetal lung maturity].

A new instrument for Pattle's microbubble test was devised in order to improve the diagnosis of fetal lung maturity. This instrument consists of 4 needles fixed at 8mm intervals and an air pump. Microbubbles were produced in 175 microliter of amniotic fluid placed on a slide glass by injecting 10 ml of air at 400 ml/h with an air pump through 22 gage needles. After 4 minutes, the number of stable microbubbles less than 15 um in diameter were counted in 5 microscope fields. When over 6 microbubbles were observed, fetal lung maturity was diagnosed as positive. 72 samples of amniotic fluids were tested by our method as well as the other 5 methods. The percentage of accurate diagnostic results was 97.2% with our method, 93.1% with the L/S ratio, 83.3% with the DSPC method, 86.1% with the PG method, 93.1% with the shake method, and 94.4% with the Pattle's original method. It is concluded that ours is a reliable, rapid and simple method for evaluating fetal lung maturity.

Female↗

PubMed1987

Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro.

When N2 microbubbles are stirred in platelet-rich plasma, they cause a fall in the number of free platelets. Changes in the platelets ultrastructure during this interaction between gas bubbles and platelets have been studied by transmission and scanning electron microscopy. Platelets, and aggregates of platelets, adhere to the surface of the N2 microbubbles. This adhesion induces ultrastructural changes (shape change, pseudopod formation, granule centralization, fusion, and disappearance) that are similar to "classical" agonists like ADP, collagen, and thrombin. These ultrastructural studies further strengthen our previous contention that N2 microbubbles activate platelets in a way similar to these physiologic agonists, and show that the previously reported fall in the number of free platelets is due to platelet aggregation. Platelet aggregates are also present in the interstices between gas bubbles. Fixed N2 microbubbles have been demonstrated, and these can be broken like cracked eggs by means of the electron beam in the electron microscope. Possible mechanisms for activation of the platelets by the gas bubbles are: through ADP released from some few platelets; by diffusion of gas after bubble-platelet interaction; and through certain fractions of the plasma proteins and lipids in the bubble surface that may act as binding sites for the platelets and promote adhesion and spreading of the platelets over the surface.

Blood Platelets↗

PubMed2004

Evaluation of surfactant function at birth determined by the stable microbubble test in term and near term infants with respiratory distress.

UNLABELLED: Surfactant function using the stable microbubble test (SMT) was investigated in term or near term infants with respiratory distress. Newborn infants > or = 34 weeks gestation with an initial clinical hypothesis of transient tachypnoea of the newborn (TTN) needing supplemental oxygen and controls were included. Gastric aspirates were collected immediately after birth for SMT. The first chest X-ray films were examined by three independent radiologists and according to their interpretation the babies were divided into a TTN, a respiratory distress syndrome of the newborn (RDS), or a poorly-defined X-ray group. A total of 32 infants with respiratory distress and 32 controls with similar gestational age and birth weight were studied. The median and interquartile range (IQR) of the stable microbubble (SMB) count was significantly lower (P < 0.001) for the respiratory distress group than for the control group (17; range 6-33 versus 120; range 79-275). The proportion of babies with less than 35 stable microbubbles/mm2 (SMB/mm2) was significantly different for the whole respiratory distress group (24/32-75%) and for the TTN (9/13-69%), the RDS (5/5-100%), and the poorly-defined (10/12-83%) groups as compared with the controls (2/32-6%; P < 0.05). A total of 24/26 babies (92%) who needed oxygen for > or = 24 h but only 1/6 (17%) of them who needed < 24 h had a bubble count of less than 35 SMB/mm2 (P < 0.05). CONCLUSION: the results suggest that deficiency or dysfunction of the surfactant system is involved in the majority of cases of respiratory distress in near term and possibly term babies. The stable microbubble test can enable clinicians to take an earlier decision to give surfactant to term or near term infants with more severe and progressive respiratory distress.

Case-Control Studies↗

PubMedDate not supplied

Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats.

OBJECTIVE: To investigate the possibility of improving the delivery of vascular endothelial growth factor (VEGF) gene to the myocardium in rats by using ultrasound-mediated microbubble destruction (UMMD). METHODS: Fifteen male Wistar rats underwent left anterior descending coronary artery ligation in this study. The rats were divided into three groups 3 days after ligation. Ultrasound microbubble vectors (UMVs) attaching to pcD2VEGF121 gene were injected into the tail vein of rats with or without simultaneous echocardiographic microbubble destruction in two groups. The third group was used as control group. VEGF protein expression and formation of new blood vessels were evaluated by immunohistochemical technique during autopsy on 15 rats at 2 weeks after gene transformation. Microvascular density (MVD) in the area with myocardial infarction was counted under a microscope. RESULTS: VEGF protein expression and MVD in the ischemic myocardium were higher in the rats receiving UMMD than in the group that did not receive UMMD. CONCLUSION: UMMD is a noninvasive method to effectively improve the delivery of targeted genes to the heart.

Analysis of Variance↗

PubMed2004

Numerical modeling of microbubble backscatter to optimize ultrasound particle image velocimetry imaging: initial studies.

We have developed a promising non-invasive ultrasound-based method for performing particle image velocimetry (PIV) in vivo. This method, termed echo PIV, provides multi-component blood velocity data with good ( approximately 2 ms) temporal resolution. The method takes advantage of the non-linear ultrasound backscatter characteristics of small gas-filled microbubbles (ultrasound contrast) that are seeded into the blood stream. In this study, we use a numerical model to explore potential areas to focus future work in echo PIV. Ultrasound backscatter from encapsulated microbubbles was modeled using a modified Rayleigh-Plesset equation (Church model, 1995), taking into account the protein/lipid shell layer as a thick, mass-conserving incompressible fluid surrounded by incompressible blood-like fluid. The equation of motion was solved numerically to characterize the fundamental and second harmonic components of the backscattered pressure. Results show a significant advantage in using the second harmonic component for echo PIV, especially for small bubble sizes less than 3 microm in diameter at 2.2 MHz frequency. The effect of the shell thickness ranging from 10 to 500 nm on the vibration amplitude of the bubble was examined and it is shown that the presence of the shell requires mechanical index (MI) > 0.2 of incident pressure amplitude to improve bubble detectability. Analysis of the effect of pulse length shows a tradeoff between axial resolution (short pulse length) and bubble detectability (longer pulse length) will most likely be required. The effect of varying MI between 0.1 and 0.6 was also studied at a center frequency of 2.2 MHz and the results indicate that the resonance of the second harmonic is maximized for bubbles with diameter of approximately 2.75 microm. Bubble non-linearities at MI > 0.2 induced a resonant frequency shift away from the integer multiple of the incident frequency in the second harmonic backscatter. For a given bubble size, there is a combination of optimal incident frequency and mechanical index range that maximizes the ratio of the second harmonic compared to the fundamental. This resonant frequency decreases with increasing bubble radius. Further, a narrow bandwidth pulse is shown to increase signal strength. Both of these effects may cause conflict with factors governing spatial resolution. Optimization of the incident frequency, microbubble size and mechanical index to enhance bubble detectability will depend on the particular clinical application. These theoretical predictions provide further understanding of the physics behind our echo PIV technique, and should be useful for guiding the design of echo PIV systems.

Blood Flow Velocity↗

PubMed2005

Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power.

A series of in vitro experiments were performed to determine the efficacy of generalised phase- and amplitude-modulated sequences for low-power nonlinear microbubble contrast imaging. The microbubble agent Definity (Dupont, Boston, MA) was exposed to sequences in which the phase and amplitude were changed from one pulse to the next. Echoes from these pulses were combined to suppress or enhance particular linear or nonlinear components. The results show that established two-pulse pulse-inversion and amplitude-modulation approaches perform similarly, providing 14 +/- 1 dB of enhancement, compared with the echoes from the linear scatterer. A two-pulse combined phase and amplitude sequence achieved an additional 4 +/- 1 dB of enhancement. This improvement is due to improved preservation of second and third order harmonic signals, while maintaining the suppression of the linear signals. These results were obtained at low power, below the threshold of microbubble destruction, and are applicable to real-time perfusion imaging.

Contrast Media↗

PubMed2005

Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo.

Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic (viz., inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g., occlusion of at-risk gastric varices.

Animals↗

PubMed2005

Absolute measurement of ultrasonic backscatter from single microbubbles.

Good quality acoustical experiments are needed to measure microbubble behavior. An absolute calibration of the transmitted ultrasound field is possible using a calibrated hydrophone, but characterization of the received ultrasound beam is a more elaborate process and is not described in the literature. A new system based on a hydrodynamically focused flow has been used to measure echoes from single microbubbles at well specified positions in the ultrasonic field. An experimental set-up was built around a commercial scanner (Sonos 5500, Philips Medical Systems) to measure the scatter from solid spheres with radii between 30 to 60 microm. The behavior of these linear scatterers is accurately predicted by theory and software was produced to incorporate a simulation of the experimental conditions. The calibration of a phased array transducer was achieved by quantifying the receiver's spectral sensitivity for the range of receive frequencies (1.2 to 4.5 MHz). Examples of echoes from the microbubble agent Definity are used to illustrate the implementation of the calibration technique.

Algorithms↗

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↗

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↗