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PubMed2000

B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans.

Pulse- or phase-inversion ultrasonography (US) sums the signals returned from two 180 degrees ultrasound pulses. Linear scattering from tissue results in a signal void while nonlinear signals from microbubbles stand out. The technique was applied with a US contrast agent in 39 human subjects. B-mode enhancement of vessels and organ parenchyma was seen in all cases. Enhancement occurred from flowing and stationary microbubbles. The flow-independent enhancement of normal and abnormal tissue represents a major advance in contrast material-enhanced US with many potential applications especially in tumor imaging.

Adult↗

PubMed1995

Albumin microbubble echo-contrast material as an enhancer for ultrasound accelerated thrombolysis.

BACKGROUND: Recent findings suggest that acoustic cavitation is responsible for acceleration of thrombolysis by ultrasound (US) energy. It is known that albumin microbubbles lower the threshold of acoustic cavitation production. METHODS AND RESULTS: The present study was designed to determine whether the presence of albumin microbubbles used for echo-contrast material (Albunex) can further accelerate fibrinolysis of US. Artificial thrombus was produced by Chandler's loop method with blood extracted from a healthy subject. Urokinase (UK, 1200 IU/mL) was added to the artificial thrombi placed in test tubes. Each thrombus was exposed to US (170 kHz) at a distance of 1.2 cm for a total of 60 seconds at an intensity of 0.5 W/cm2 at intervals of 2 seconds on and 4 seconds off. Echo-contrast material (0.6 x 10(6) microspheres per mL) or 5% albumin (for control) was circulated near the thrombus at a rate of 1 mL/min during the US exposure. Fibrinolysis was later determined by percentage of weight loss of thrombus after 60 minutes of incubation (n = 15). Fibrinolysis with UK alone was 26.6 +/- 4.8%. Fibrinolysis with UK+US treatment was 33.3 +/- 5.8%. Further increase of fibrinolysis to 51.3 +/- 7.7% occurred in the presence of Albunex (UK+US+Albunex). Statistical differences were obtained between all these groups (ANOVA). CONCLUSIONS: The presence of the echo-contrast agent induced further acceleration of thrombolysis by US energy. It is suggested that this diagnostic echo-contrast material can be used as an alternative therapeutic US drug enhancer for thrombolysis.

Adult↗

PubMed1995

Transient myocardial contrast after initial exposure to diagnostic ultrasound pressures with minute doses of intravenously injected microbubbles. Demonstration and potential mechanisms.

BACKGROUND: We have observed a transient but significant increase in myocardial contrast intensity with intravenously injected perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles that occurs on initial exposure to pulsed ultrasound (transient-response imaging). The characteristics and magnitude of this response were examined in the present study. METHODS AND RESULTS: In 14 dogs, the myocardial contrast intensity produced by transient-response imaging (TRI) was compared with conventional 30-Hz imaging (CI) after a 0.005 to 0.030 mL/kg intravenous injection of PESDA. TRI was produced either by measuring myocardial contrast during triggered (1 pulse per cardiac cycle) ultrasound or by withholding real time ultrasound transmission until after microbubbles had entered the myocardium after intravenous injection. Both first-harmonic imaging (2.0 to 3.5 MHz) and second-harmonic imaging (2.0 to 2.5 MHz fundamental, 4.0 to 5.0 MHz received) were used. TRI produced over three times the anterior myocardial contrast intensity of CI (36 +/- 12 U TRI versus 11 +/- 11 U CI; P < .01), with visually better anterior and posterior myocardial contrast. The spatial extent of myocardial ischemia was easily visualized after intravenous PESDA by use of TRI and correlated closely with risk area as measured with Monastral blue (r = .99, P = .002). CONCLUSIONS: TRI produces significantly greater myocardial contrast than CI and may dramatically enhance the ability of intravenous ultrasound contrast agents to identify myocardial perfusion abnormalities.

Animals↗

PubMed1998

Noninvasive in vivo clot dissolution without a thrombolytic drug: recanalization of thrombosed iliofemoral arteries by transcutaneous ultrasound combined with intravenous infusion of microbubbles.

BACKGROUND: Previous in vivo studies have shown that microbubbles not only enhance the effectiveness of thrombolytic agents in the presence of ultrasound but may also augment clot dissolution without thrombolytic drugs. METHODS AND RESULTS: The objective of this study was to examine the efficacy of arterial clot disruption by a noninvasive, nonlytic approach with intravenous administration of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) and transcutaneous delivery of ultrasound alone. Pairs of iliofemoral arteries in 10 rabbits were randomized to receive transcutaneous ultrasound treatment or no ultrasound treatment after an acute artery thrombotic occlusion and intravenous PESDA infusion. Five arteries from 3 additional rabbits served as controls (ultrasound alone). All 10 iliofemoral arteries treated with PESDA + ultrasound were recanalized by angiography after ultrasound treatment. None of the 10 contralateral arteries treated with PESDA alone and none of the 5 arteries treated with ultrasound alone were patent after 1 hour. D-Dimer levels did not change after intravenous PESDA + ultrasound-mediated reperfusion. CONCLUSIONS: In vivo arterial clot dissolution can be achieved with intravenous microbubbles and transcutaneous ultrasound delivery alone. This technique has potential for clinical application in patients with acute arterial and venous thrombotic occlusions.

Animals↗

PubMed2003

Improved detection of microbubble signals using power M-mode Doppler.

UNLABELLED: Background- Power motion-mode transcranial Doppler (TCD) (PMD) is a new, multigated technique that may simplify and enhance detection of embolus. We developed criteria for emboli detection using PMD. Then, we performed a blinded comparison of transcranial PMD with single-gate spectral TCD in TCD bubble study patients. METHODS: Patients with right-to-left shunt as detected with standard TCD were selected for this study. The international emboli criteria for spectral TCD were used. We defined novel PMD criteria for detecting emboli signature on PMD as follows: (1) signature at least 3 dB higher than the highest spontaneous PMD display of background blood flow; (2) embolic signature reflects motion in one direction at a minimum spatial extent of 7.5 mm and temporal extent of 30 ms; (3) embolus must traverse a prespecified depth. Each study was blindly assessed for microbubble signals (MBS) count on either modality. RESULTS: Thirty-six patients were included in the study. Mean age was 44.4 (SD 14.4), 50% were male, and median time from stroke onset to TCD bubble test was 12 days. Median MBS count in middle cerebral arteries (MCA) was 4 on both modalities. Spectral TCD MBS counts were highly correlated (rho=0.97) with PMD MBS counts in MCA and similarly in anterior cerebral arteries (ACA) (rho=0.79). When PMD microbubble counts in the ACA and MCA were summed, a clear 2-fold difference emerged between 2 modalities (P<0.001). CONCLUSIONS: When compared with spectral TCD, PMD detects more MBS with higher counts by identifying ACA as well as MCA emboli. Pitfalls of overcounting emboli with PMD can be avoided by following such criteria.

Adult↗

PubMed2000

Contrast transcranial doppler ultrasound in the detection of right-to-left shunts : time window and threshold in microbubble numbers.

BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation procedure. Currently, data on the appropriate timing of the VM, the use of a diagnostic time window, and a threshold in contrast agent microbubbles detected are insufficient. METHODS: Fifty-eight patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with injections of 10 mL of the commercial galactose-based contrast agent Echovist was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds after the beginning of contrast injection, (3) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, (4) VM for 5 seconds starting 8 seconds after the beginning of contrast injection, and (5) repetitive short VMs in between 2 and 13 seconds after the beginning of contrast injection. In addition to the single tests, we also tested the sensitivity and specificity of combined results of the tests with VM. RESULTS: In 21 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 16 patients were only positive on at least 1 TCD investigation but negative during TEE. Test 3 was the most appropriate test when combined with the results of 1 of the other tests with VM. The highest sensitivities were achieved with a diagnostic time window of 40 seconds and when the presence of a single microbubble was sufficient for the diagnosis of a shunt. CONCLUSIONS: TCD performed twice with 2 provocation maneuvers with Echovist is a sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM should be performed for 5 seconds starting at 5 seconds after the beginning of contrast injection.

Adolescent↗

PubMed2001

Destruction of contrast microbubbles by ultrasound: effects on myocardial function, coronary perfusion pressure, and microvascular integrity.

BACKGROUND: Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. METHODS AND RESULTS: To examine the functional and morphological significance of these findings in the heart, isolated rabbit hearts were perfused retrogradely with buffer containing ultrasound contrast agents and were insolated at increasing levels of acoustic energy with a broadband transducer emitting at 1.8 MHz and receiving at 3.6 MHz and operated in the triggered mode (1 Hz). At the end of each experiment, the hearts were fixed in glutaraldehyde and examined with light microscopy. Neither exposure to ultrasound alone or to contrast alone affected left ventricular developed pressure. By contrast, simultaneous exposure to contrast and ultrasound resulted in a reversible, transient mechanical index (MI)-dependent decrease in left ventricular developed pressure (to 83+/-5% of baseline at an MI of 1.6) and a transient MI-dependent increase in coronary perfusion pressure (to 120+/-6% of baseline at an MI of 1.6). Myocardial lactate release also showed significant increases with increasing MIs. Macroscopically, areas of intramural hemorrhage were identified over the beam elevation in hearts exposed to both contrast and high-MI ultrasound. Light microscopy revealed the presence of capillary ruptures, erythrocyte extravasation, and endothelial cell damage. The mean percentage of capillaries ruptured at an MI of 1.6 was 3.6+/-1.4%. CONCLUSIONS: Simultaneous exposure of isolated rabbit hearts to ultrasound and contrast agents results in an MI-dependent, transient depression of left ventricular contractile function, a rise in coronary perfusion pressure, an increase in lactate production, and limited capillary ruptures.

Animals↗

PubMed2004

Elimination of microbubbles from the extracorporeal circuit: dynamic bubble trap versus arterial filter.

BACKGROUND: Open heart surgery is associated with important risk of cerebral and peripheral organ dysfunction, attributed in part to microbubbles generated in or not eliminated from the ECC. For elimination of microbubbles, a dynamic bubble trap (DBT) was developed for the arterial line of ECCs. METHODS: Bubble eliminating properties of an arterial filter were evaluated in four CABG patients and compared to the performance of the DBT in four patients. One patient received both devices. RESULTS: Elimination of bubbles between 40-120 microm was significantly higher with the DBT (88% vs. 57% with arterial filter, p=0.034). Reduction of bubbles below 40 microm was equivalent in both groups. The combination of both devices was most effective (94% for bubbles >40 microm). CONCLUSION: Arterial filter and DBT are equally effective in elimination of smaller gas bubbles. However, bigger bubbles possibly causing cerebral and peripheral organ damage are eliminated to a greater degree by the DBT.

Coronary Artery Bypass↗

PubMed2000

Unfolding of poly-L-glutamic acid by microbubbling of supercritical carbon dioxide.

The conformational changes in alpha-helical poly-L-glutamic acid caused by microbubbling supercritical CO2 were investigated with circular dichroism spectra. After microbubbling using a micropore filter at 35 and 30 MPa for 30 min, alpha-helix content decreased to 37%, while without the filter it was 68%. The alpha-helix structure was significantly decomposed by a high density of CO2. No important changes were observed in heating, autoclaving, or pH-lowering.

Carbon Dioxide↗

PubMed2002

Scale-up of microbubble dispersion generator for aerobic fermentation.

A laboratory-scale microbubble dispersion (MBD) generator was shown to improve oxygen transfer to aerobic microorganisms when coupled to the conventional air-sparger. However, the process was not demonstrated on a large scale to prove its practical application. We investigated the scale-up of a spinning-disk MBD generator for the aerobic fermentation of Saccharomyces cerevisiae (baker's yeast). A 1-L spinning-disk MBD generator was used to supply air for 1- and 50-L working volume fermentation of baker's yeast. For the two levels investigated, the MBD generator maintained an adequate supply of surfactant-stabilized air microbubbles to the microorganisms at a relatively low agitation rate (150 rpm). There was a significant improvement in oxygen transfer to the microorganism relative to the conventional sparger. The volumetric mass transfer coefficient, kLa, for the MBD system at 150 rpm was 765 h(-1) compared to 937 h(-1) for the conventional sparger at 500 rpm. It is plausible to surmise that fermentation using larger working volumes may further improve the kLa values and the dissolved oxygen (DO) levels because of longer hold-up times and, consequently, improve cell growth. There was no statistically significant difference between the cell mass yield on substrate (0.43 g/g) under the MBD regime at an agitation rate of 150 rpm and that achieved for the conventional air-sparged system (0.53 g/g) at an agitation rate of 500 rpm. The total power consumption per unit volume of broth in the 50-L conventional air-sparged system was threefold that for the MBD unit for a similar product yield. Practical application of the MBD technology can be expected to reduce power consumption and therefore operating costs for aerobic fermentation.

Aerobiosis↗

PubMed1997

Use of carbon dioxide microbubble-enhanced sonographic angiography for transcatheter arterial chemoembolization of hepatocellular carcinoma.

OBJECTIVE: Our objective was to determine the usefulness of sonographic angiography with carbon dioxide microbubbles during transcatheter arterial chemoembolization for hepatocellular carcinoma. SUBJECTS AND METHODS: Thirty-four patients with hepatocellular carcinoma underwent sonographic angiography during transcatheter arterial chemoembolization. Digital subtraction angiography failed to reveal tumors in 27 patients. Tumor stain became obscure on digital subtraction angiography after the catheter was inserted into distal branches in seven patients. Sonographic angiography was performed after injection of carbon dioxide microbubbles into the hepatic artery selected for transcatheter arterial chemoembolization. RESULTS: In angiographically undetectable hepatocellular carcinomas, sonographic angiography revealed tumor vascularity in 17 patients in whom transcatheter arterial chemoembolization was then performed. For the two patients who underwent a second transcatheter arterial chemoembolization, the existence of alternative feeding vessels was confirmed by sonographic angiography. In the remaining 10 patients, tumor vascularity was not seen on sonographic angiography; percutaneous ethanol injection therapy was then performed. Sonographic angiography clearly revealed tumor vascularity in patients in whom staining became obscure on digital subtraction angiography after the catheter was inserted into a peripheral branch of the hepatic artery. In all 24 patients who underwent transcatheter arterial chemoembolization, sonographic angiography was useful for determining the artery suitable for transcatheter arterial chemoembolization and for monitoring tumor perfusion in the selected artery. CONCLUSION: Sonographic angiography can be used to determine not only the therapeutic strategy for treatment of hepatocellular carcinoma but also whether the tumor is supplied by the artery selected for transcatheter arterial chemoembolization, especially when the tumor is not revealed by digital subtraction angiography.

Aged↗

PubMed2004

[Gene transfer with ultrasound and microbubbles (optison) as a potential treatment for cardiovascular diseases].

Cardiovascular diseases are the leading causes of mortality and morbidity in developed countries. Most conventional therapy is inefficient and tends to treat the symptoms rather than the underlying causes of the disorder. Gene therapy based on ultrasound with microbubbles offers a novel approach for the prevention and treatment of cardiovascular diseases. The major development of gene transfer has importantly contributed to intense investigation of the potential of gene therapy in cardiovascular medicine. The amazing advances in molecular biology have provided a dramatic improvement of the technology that is necessary to transfer target genes into somatic cells. Gene transfer methods have been surprisingly improved. In fact, some of them (retroviral vectors, adenoviral vectors or liposome based vectors, etc) have been used in clinical trials already. However, some severe side effects were reported in clinical gene therapy using such viral vector, so people wish for safe and efficient clinical gene therapy. Transfection with ultrasound and microbubbles has been reported as a new powerful tool in a new class for gene therapy.

Albumins↗

PubMed2002

Assessment of therapeutic response in hepatocellular carcinoma treated with percutaneous radio frequency ablation: comparison of multiphase helical computed tomography and power Doppler ultrasonography with a microbubble contrast agent.

OBJECTIVE: To compare the results of multiphase helical computed tomography and power Doppler ultrasonography with a microbubble contrast agent in the assessment of the therapeutic response to radio frequency ablation in hepatocellular carcinoma. METHODS: In 66 patients with 73 nodular hepatocellular carcinomas ranging from 1.0 to 4.0 cm (mean, 2.6 cm) in diameter, contrast-enhanced power Doppler ultrasonography was performed after intravenous bolus injection of a galactose-based microbubble contrast agent before and after radio frequency ablation. The results of the studies were compared with the findings of follow-up 3-phase helical computed tomography. All patients were regularly followed up with computed tomography for more than 1 year (range, 13-19 months). RESULTS: In 8 (11%) of 73 hepatocellular carcinomas, immediate follow-up computed tomography obtained within 2 hours after radio frequency ablation showed focal enhancing portions within the treated lesions, suggesting residual non-necrotic tumors. All 8 of these tumors had intratumoral flow signals on contrast-enhanced power Doppler ultrasonography. The diagnostic agreement between computed tomography and contrast-enhanced power Doppler ultrasonography was achieved in 100%. Among the remaining 65 hepatocellular carcinomas with the absence of residual tumors at both immediate follow-up computed tomography and contrast-enhanced power Doppler ultrasonography, subsequent follow-up computed tomography showed local regrowth at the margins of 10 lesions (15%). CONCLUSIONS: The results of contrast-enhanced power Doppler ultrasonography closely correlated with those of immediate follow-up computed tomography for detecting residual tumors in hepatocellular carcinomas treated with radio frequency ablation. Both techniques, however, showed a limitation in detecting small or microscopic residual tumors and in predicting local regrowth in the treated lesions.

Adult↗

PubMed2003

Early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma: utility of gray scale harmonic ultrasonography with a microbubble contrast agent.

OBJECTIVE: To evaluate the utility of gray scale harmonic ultrasonography with a microbubble contrast agent in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma. METHODS: Seventy-five patients with 81 nodular hepatocellular carcinomas (1.3-4.8 cm) treated with percutaneous radio frequency ablation were evaluated with contrast-enhanced gray scale harmonic ultrasonography after intravenous bolus injection of a galactose-based microbubble contrast agent. The vascularity within the ablation zones was evaluated with a continuous scan for 3 to 5 seconds between 15 and 30 seconds after initiation of contrast agent injection. To evaluate the perfusion of the ablation zones, intermittent stimulated acoustic emission imaging was performed with a rapid sweeping technique from the end of the continuous scan. All patients underwent follow-up 3-phase helical computed tomography at 1 month after radio frequency ablation and were followed for at least 1 year. The results of contrast-enhanced ultrasonography were compared with those of follow-up computed tomography in terms of the presence or absence of residual unablated tumors. RESULTS: In 10 (12%) of the 81 treated hepatocellular carcinomas, contrast-enhanced ultrasonography showed either nodular or crescentic enhancing foci at the margins of ablation zones, suggesting residual unablated tumors. Contrast-enhanced computed tomography obtained 1 month after radio frequency ablation confirmed the residual unablated tumors in the same 10 lesions. Diagnostic agreement between 1-month follow-up computed tomography and contrast-enhanced ultrasonography was achieved in all 81 cases (100%). CONCLUSIONS: Contrast-enhanced gray scale harmonic ultrasonography can be a reliable alternative to contrast-enhanced computed tomography in the early assessment of the therapeutic response to radio frequency ablation for hepatocellular carcinoma.

Adult↗

PubMedDate not supplied

Microbubble retention and failed macular hole surgery.

This case reports a possible new cause of failed macular hole surgery. Standard macular hole surgery with removal of epiretinal membranes, 16% C3F8, and strict postoperative prone positioning was performed on a patient with stage 4 macular hole. Macular hole surgery failed with retention of a microbubble of C3F8 within the macular hole during the follow-up period. Retention of a microbubble within a macular hole may prevent closure of the hole and be a previously unrecognized cause of failed macular hole surgery.

Epiretinal Membrane↗

PubMed2006

[In vivo transduction of EGFP into female mouse reproductive system by electroporation and microbubble-enhanced sonoporation].

In the present study, the efficiency of in vivo transduction of EGFP plasmid DNA into adult female mouse reproductive system by means of electroporation and microbubble-enhanced sonoporation are discussed. In the first experiment,EGFP plasmid DNA was injected into the ovary and following electroporation (square electric pulses were applied five times at 60V with a constant time of 20ms). Green fluorescence was detected 10h after transduction. In the second experiment, plasmid DNA was mixed with the microbubble at different ratio and injected into the uterus and the ovary separately. The tissues were exposed to different combined ultrasound parameters immediately after injection. We found that the suitable parameter was 2 w/cm2 intensity, 20% duty cycle and 5min. Under this condition, green fluorescence was expressed in the uterus endometrium and ovarian cortex 12 h post-sonoporation and the expression lasted up to 5 days.

Animals↗

PubMed1989

Contrast echocardiography: effects of microbubbles on coronary blood flow and left ventricular hemodynamics.

Contrast echocardiography is currently being used to define and quantitate myocardial perfusion at the time of cardiac catheterization. Limited and conflicting data exist regarding the physiologic effects of microbubble-containing contrast agents. In the present study, coronary blood flow measured using an electromagnetic flow meter, blood pressure, and heart rate responses were studied in six dogs. An ECG-gated power injector was used to deliver 7 to 9 ml of sonicated and nonsonicated solutions (saline, Renografin-76, dextrose 50% and 70%, and sorbitol 70%) through an intra-aortic catheter placed above the aortic cusps. Paired injections of sonicated and nonsonicated agents were compared to determine whether the presence of microbubbles affected the physiologic response to these agents. Simultaneous recordings of two-dimensional cross-sectional images of the left ventricle were obtained. Data are expressed as percentage of change from preinjection control values. Within 10 seconds of an injection, decreases in coronary blood flow occurred in a range from -1 to -10% compared with preinjection control values. Coronary blood flow increased between 10 and 25 seconds postinjection within a range from +11 to +29%. Systemic blood pressures rose during injections and then declined below control values within 10 seconds. The magnitude of the decline in systolic blood pressure ranged from -5. to -18%. Diastolic blood pressure declined in a range from -13 to -33%. Within 20-30 seconds postinjection, systemic blood pressure rose above control values. The magnitude of the systolic and diastolic blood pressure rise ranged from +4 to +11%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Myocardial contrast echocardiography: examination of intracoronary injections, microbubble diameters, and video-intensity decay.

Contrast echocardiographic assessment of blood flow within the myocardium requires standardization of contrast agents and echo image analysis. Sonicated contrast solutions containing small and relatively stable microbubble ultrasound reflectors were injected into coronary arteries of five dogs, and a newly developed computer assisted densitometric analysis of myocardial echo intensity decay was examined. The sonicated solutions included sorbitol 70%, dextrose 70%, and dextrose 50%, and myocardial contrast echo data were analyzed by applying an exponential decay index (T-1/2) to the digitized time intensity curves obtained with videodensitometric techniques. In 30 intracoronary injections selected for further analysis, sonicated sorbitol 70% demonstrated the most physiologic myocardial transit time with the smallest variability (6.0 +/- 2.0 seconds). Sonicated dextrose 70% and dextrose 50% solutions exhibited significantly prolonged and more variable transit times (11.4 +/- 4.0 seconds and 13.9 +/- 5.0 seconds). The results of this study suggest that appropriate echo contrast solutions with small microbubble diameters are critical to satisfactory echocardiographic assessment of myocardial blood flow, and that objective analysis of contrast two-dimensional echocardiographic images can be achieved with computer-assisted videodensity algorithms featuring standardized echo analysis of the time intensity data.

Animals↗