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PubMed2006

Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA.

Ultrasound in combination with microbubbles has recently been considered by gene delivery scientists to be an interesting approach to enhance gene transfer into cells. Its low toxicity and simplicity to apply in vivo without major complications make this technology (sonoporation) especially attractive. Sonoporation of DNA has been evaluated in vivo by the injection of free plasmid DNA (pDNA) together with microbubbles (as used in diagnostic imaging) in the bloodstream. However, the in vivo gene-transfer efficiency in these experiments remained rather low. Both the enzymatic degradation of the injected pDNA as well as the low pDNA concentration in the neighborhood of sonoporated cell membranes may explain this low efficiency. Therefore, we developed polymer-coated microbubbles that can bind and protect the pDNA. Coating albumin-shelled microbubbles with poly(allylamine hydrochloride) (PAH) makes the surface charge of the microbubbles positive without drastically affecting the size distribution of the microbubbles, thereby not affecting the ultrasound responsiveness and injectability. The cationic coating allowed both to bind up to 0.1 pg of DNA per microbubble as well as to protect the bound DNA against nucleases. Finally, the PAH coating significantly increased the lifetime of the microbubbles (half-life approximately 7 h), making them more convenient for in vivo applications because more microbubbles are expected to reach the target organ. Binding and nuclease protection of DNA by polymer-coated diagnostic microbubbles has, to our knowledge, never been demonstrated. We conclude that these LbL-coated microbubbles might be significant in the further development of ultrasound-mediated gene delivery.

DNA↗
PubMed2006

Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

OBJECTIVES: Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. MATERIALS AND METHODS: Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. RESULTS: Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. CONCLUSION: Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

Animals↗
PubMed2004

Preparation of human hepatocellular carcinoma-targeted liposome microbubbles and their immunological properties.

AIM: To prepare the human hepatocellular carcinoma-(HCC)-targeted liposome microbubbles and to investigate their immunological properties. METHODS: Human hepatocarcinoma specific monoclonal antibody HAb18 was attached to the surface of home-made liposome microbubbles by static attraction to prepare the targeted liposome microbubbles. The combination of HAb18 with liposome microbubbles was confirmed by the slide agglutination test and immunofluorescent assay. Their immunological activity was measured by ELISA. Rosette formation test, rosette formation blocking test and immun-ofluorescent assay were used to identify the specific binding of targeted liposome microbubbles to SMMC-7721 hepatoma cells, and cytotoxicity assay was used to detect their effect on human hepatocytes. RESULTS: The targeted liposome microbubbles were positive in the slide agglutination test and immunofluorescent assay. ELISA indicated that the immunological activity of HAb18 on the liposome microbubbles was similar to that of free HAb18. SMMC-7721 cells were surrounded by the targeting liposome microbubbles to form rosettes, while the control SGC-7901 gastric cancer cells were not. Proliferation of SMMC-7721 cells and normal human hepatocytes was not influenced by the targeted liposome microbubbles. CONCLUSION: The targeted liposome microbubbles with a high specific biological activity have been successfully prepared, which specifically bind to human hepatocarcinoma cells, and are non-cytotoxic to hepatocytes. These results indicate that the liposome microbubbles can be used as a HCC-targeted ultrasound contrast agent that may enhance ultrasound images and thus improve the diagnosis of HCC, especially at the early stage.

Antibodies, Monoclonal↗
PubMed1999

Microbubbles associated with mechanical heart valves: their relationwith serum lactic dehydrogenase levels.

BACKGROUND: There has been no consensus about the prevalence and mechanism of generation of microbubbles in mechanical prosthetic heart valves (PHV). The aim of this study was to determine the prevalence of microbubbles in PHV and their relation to serum lactic dehydrogenase (LDH) levels. METHODS AND RESULTS: We prospectively studied 150 normally functioning mitral PHV (98 bileaflet and 52 monoleaflet) in 150 patients with the use of transesophageal echocardiography with a multiplane 5-MHz probe. None of the patients had an aortic prosthetic valve. Blood was drawn to determine serum LDH level. None of the patients had any factors that might affect the LDH level other than the PHV-related hemolysis. Patients with spontaneous echo contrast in the left atrium that might affect the assessment of the microbubbles were excluded. We devised a method to determine the amount of microbubbles for each PHV. Microbubbles were detected in 118 (79%) of 150 PHV, including 97 (99%) of 98 bileaflet valves and 21 (40%) of 52 monoleaflet (tilting disk) valves (P <. 0001). Intraobserver variability was not statistically significant for the determination of the amount of microbubbles (z = 1.7, P =. 08). There was a strong correlation between serum LDH levels and the amount of microbubbles (rs = 0.69, P <.001). CONCLUSIONS: Microbubbles were detected in more patients than reported previously. They were found to be associated more with the bileaflet than the monoleaflet PHV. Sorin monoleaflet valves were associated with microbubbles significantly less often than the others. There was a strong correlation between serum LDH levels and microbubble counts, which suggests that hemolysis may be related to microbubble formation.

Adult↗
PubMed2002

Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi.

RATIONALE AND OBJECTIVES: New targeted microbubbles directed to the GPIIb IIIa receptor have been developed. The objective was to determine whether targeting microbubbles to clots would enhance ultrasound imaging. Systematic studies were designed to determine whether in vitro methodology is an acceptable predictor of in vivo efficacy. MATERIALS AND METHODS: Bioconjugate ligands were inserted into lipid-coated membranes of perfluorocarbon gas microbubbles and binding studies performed on activated platelets immobilized on cell culture plates. Targeted microbubble binding to clots in a flow through chamber was also assessed. Finally, microbubble binding studies on arteriolar and venular clots in a mouse cremasteric muscle model were conducted. RESULTS: Binding studies on platelet-immobilized plates demonstrated an affinity for targeted microbubbles versus untargeted microbubbles. Semiquantitative light obscuration techniques helped to measure extent of targeted microbubble binding. Targeted microbubbles similarly bound to platelet clots in the flow model. Finally, studies in the mouse model confirmed binding of targeted microbubbles in both venules and arterioles. CONCLUSION: The use of receptor selective targeted microbubbles improved binding to vascular thrombi in both in vitro and in vivo settings.

Animals↗
PubMed1998

Sonographic comparison of intraarterial CO2 and helium microbubbles for detection of hepatocellular carcinoma: preliminary observations.

PURPOSE: To evaluate the usefulness of helium gas microbubbles in the detection of small hepatocellular carcinoma (HCC) lesions relative to that of CO2 microbubbles. MATERIALS AND METHODS: Ultrasonography (US) enhanced with both CO2 microbubbles and helium microbubbles was performed in 15 patients. CO2 microbubbles were injected into the proper hepatic artery under US observation. Next, helium microbubbles were injected. Duration and degree of enhancement with the two types of microbubbles were compared. Ten minutes after helium injection, the whole liver was examined with US to detect additional tumors. When new lesions were detected, biopsy was performed. RESULTS: Duration of enhancement with the helium microbubbles (mean, 37.2 minutes) was significantly longer than that with the CO2 microbubbles (mean, 3.6 minutes; P < .001). The degree of enhancement with helium was greater than that with CO2. Thirteen additional lesions were detected after injection of helium gas. All these lesions proved to be HCC at biopsy. CONCLUSION: The duration of enhancement is significantly longer with helium than with CO2 microbubbles. Therefore, helium microbubbles can be used for examination of the whole liver for detection of additional tumors.

Carbon Dioxide↗
PubMed2000

Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes.

BACKGROUND: Lipid microbubbles used for perfusion imaging with ultrasound are retained within inflamed tissue because of complement-mediated attachment to leukocytes within venules. We hypothesized that incorporation of phosphatidylserine (PS) into the microbubble shell may enhance these interactions by amplifying complement activation and thereby allow ultrasound imaging of inflammation. METHODS AND RESULTS: In 6 mice, intravital microscopy of tissue necrosis factor-alpha-treated cremaster muscle was performed to assess the microvascular behavior of fluorescein-labeled lipid microbubbles with and without PS in the shell. Ten minutes after intravenous injection, microbubble attachment to leukocytes within inflamed venules was greater for PS-containing than for standard lipid microbubbles (20+/-4 versus 10+/-3 per 20 optical fields, P<0.05). The ultrasound signal from retained microbubbles was assessed in the kidneys of 6 mice undergoing renal ischemia-reperfusion injury and in 6 control kidneys. The signal from retained microbubbles in control kidneys was low (<2.5 video intensity units) for both agents. After ischemia-reperfusion, the signal from retained microbubbles was 2-fold higher for PS-containing than for standard lipid microbubbles (18+/-6 versus 8+/-2 video intensity units, P<0.05). An excellent relation was found between the ultrasound signal from retained microbubbles and the degree of renal inflammation, assessed by tissue myeloperoxidase activity. CONCLUSIONS: -We conclude that noninvasive assessment of inflammation is possible by ultrasound imaging of microbubbles targeted to activated leukocytes by the presence of PS in the lipid shell.

Animals↗
PubMed2006

Prevalence and clinical significance of pleural microbubbles in computed tomography of thoracic empyema.

AIM: To determine the prevalence and clinical significance of pleural microbubbles in thoracic empyema. MATERIALS AND METHODS: The charts of 71 consecutive patients with empyema were retrospectively reviewed for relevant demographic, laboratory, microbiological, therapeutic and outcome data. Computed tomography (CT) images were reviewed for various signs of empyema as well as pleural microbubbles. Two patient groups, with and without microbubbles were compared. RESULTS: Mean patient age was 49 years and 72% were males. Microbubbles were detected in 58% of patients. There were no significant differences between patients with and without microbubbles in regard to pleural fluid chemistry. A causative organism was identified in about 75% of cases in both. There was no difference in the rates of pleural thickening and enhancement, increased extra-pleural fat attenuation, air-fluid levels or loculations. Microbubbles were diagnosed after a mean of 7.8 days from admission. Thoracentesis before CT was performed in 90 and 57% of patients with and without microbubbles (p=0.0015), respectively. Patients with microbubbles were more likely to require repeated drainage (65.9 versus 36.7%, p=0.015) and surgical decortication (31.7 versus 6.7%, p=0.011). Mortalities were 9.8 and 6.6% respectively (p=0.53). CONCLUSION: Pleural microbubbles are commonly encountered in CT imaging of empyema but have not been systematically studied to date. Microbubbles may be associated with adverse outcome such as repeated drainage or surgical decortication. The sensitivity and specificity of this finding and its prognostic implications need further assessment.

Air↗
PubMed2007

Effect of ultrasound-activated microbubbles on the cell electrophysiological properties.

New clinical applications of ultrasound contrast microbubbles extend beyond imaging and diagnosis toward therapeutic applications. Cell membrane permeability and the uptake of substances have been shown to be enhanced by microbubbles under ultrasound stimulation. However, the mechanisms of action of ultrasound-activated microbubbles are still unknown. The aim of our study was to examine how microbubbles and ultrasound interact with cells in an attempt to understand the sonoporation mechanism. The ruptured-patch-clamp whole-cell technique was used to measure membrane potential variations of a single cell. SonoVue microbubbles and mammary breast cancer cell line MDA-MB-231 were used. Ultrasound was applied using single-element transducers of 1 MHz. Microbubbles and cells were simultaneously video monitored during ultrasound exposure. Our results showed that, during sonoporation, a marked cell membrane hyperpolarization occurs (n = 6 cells) at negative pressures above 150 kPa, indicating the activation of specific ion channels while the cell and the microbubbles remain viable. The hyperpolarization was sustained for as long as the microbubbles are in a direct contact with the cell and the ultrasound waves are transmitted. Smaller acoustic amplitudes induced only mild hyperpolarization, whereas shutting off the ultrasound brings the cell membrane potential to its resting value. However, ultrasound alone did not affect the cell membrane potential. A similar hyperpolarization of the cell membrane was observed when a mechanical pressure was applied on the cell through a glass probe. In conclusion, the results demonstrate that microbubbles' oscillations under ultrasound activation entail modifications of the electrophysiologic cell activities by triggering the modulation of ionic transports through the plasmic cell membrane. However, only cells in direct contact with the microbubbles are impacted. The mechanisms involved are likely related to activation of specific channels sensitive to mechanical stresses (stretch-activated channels) and possibly nonspecific ion channels.

Cell Line, Tumor↗
PubMed2004

Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles.

RATIONALE AND OBJECTIVES: During echo examinations with microbubble contrast, individual "dots" of ultrasound reflection can be visualized. To address the question whether these signals represent individual microbubbles, very dilute suspensions of ultrasound contrast agents or individual microbubbles attached to Petri dishes were prepared and studied by ultrasound imaging. METHODS: Microbubble suspensions were diluted in saline and evaluated by a clinical ultrasound imaging system. Microbubble concentration was verified by Coulter counter. Single microbubble preparation on a Petri dish was established by streptavidin-biotin interaction under microscopy control and subjected to ultrasound imaging. RESULTS: Ultrasound of dilute microbubble dispersions demonstrated distinct white foci; concentration of these sites was consistent with signals from individual microbubbles as determined by Coulter. Individual microbubbles immobilized on polystyrene were also visualized by ultrasound. CONCLUSION: Ultrasound medical systems can resolve backscatter signals from individual microbubbles of ultrasound contrast, both in solution and in the targeted immobilized state, implying picogram sensitivity.

Contrast Media↗
PubMed1994

Spontaneously appearing microbubbles associated with prosthetic cardiac valves detected by transesophageal echocardiography.

During transesophageal echocardiographic studies in patients with prosthetic cardiac valves, we have noticed the presence of bright, highly mobile echoes (termed microbubbles because of their similarity to saline contrast bubbles) that move rapidly away from the valve. These echoes are distinct from spontaneous echo contrast. The purpose of this study was to determine the frequency with which microbubbles are detected in association with prosthetic valves. No microbubbles were detected in association with bioprosthetic valves. Thus analysis was limited to 198 studies performed in 138 patients with left-sided mechanical valves. Microbubbles were detected in 69 (35%) studies. No differences were found between studies with and without microbubbles with regard to patient characteristics or the indication for the study. Among the 173 individual valves studied, microbubbles were more frequently detected in association with mitral valves (34 of 82, 41%) versus aortic valves (14 of 91, 15%; p 0.0001). Microbubbles were more frequently detected with disc-type mitral valves (30 of 42, 17%) in comparison to Starr-Edwards mitral valves (4 of 39, 10%; p 0.0001). Microbubbles were more often detected with abnormal valves (28 of 76, 37%) than normal valves (20 of 97, 21%), p 0.02. We conclude that bright, highly mobile echoes (microbubbles) distinct from spontaneous echo contrast are frequently detected during transesophageal echocardiography in association with mechanical prosthetic valves. Although the cause and clinical significance of these microbubbles are unknown, it is important to distinguish these echoes from valvular masses such as thrombus or vegetations.

Aortic Valve↗
PubMed2004

Therapeutic applications of lipid-coated microbubbles.

Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.

Blood-Brain Barrier↗
PubMed2000

Optimization of the size distribution and myocardial contrast effect of perfluorocarbon-filled albumin microbubbles by lyophilization under continuous negative pressure.

This study was undertaken to evaluate the effect of lyophilization under continuous negative pressure on perfluoropropane-filled albumin microbubble size distribution and myocardial contrast effect. Three different microbubble preparations were studied: (1) 1% albumin solution without a sugar (Optison), (2) 1% albumin and 5% dextrose (PESDA), and (3) 1% albumin and 5% fructose (PESFA). The 2 preparations containing sugar were also subjected to lyophilization under continuous negative pressure. Microbubble size distribution was measured with a Coulter Multisizer II (Beckman Coulter, Inc, Fullerton, Calif). The microbubbles were injected intravenously into a rat during intravital microscopy of the mesenteric microcirculation. Finally, the different albumin microbubbles were injected intravenously into 10 dogs, and myocardial contrast effect was assessed by videodensitometry. Results of the Coulter counter studies showed lyophilized PESFA to have a smaller size distribution with 99.9% + or - 0.1% of microbubbles <10 microm in diameter and 88.5% + or - 1.4% <4 microm in diameter (P <.05 compared with Optison or PESDA). On intravital microscopy, PESFA microbubbles behaved as intravascular tracers without microvascular plugging or coalescence. Finally, myocardial peak gray scale and area under the curve were significantly higher for PESFA than for PESDA or Optison, respectively. In conclusion, lyophilization of perfluoropropane-filled albumin microbubbles results in smaller microbubbles with a more uniform size distribution and brighter myocardial contrast. In addition, the substitution of fructose for dextrose improves size distribution and contrast effect. These findings have important implications regarding the use of novel imaging technologies that take advantage of microbubble destruction to image myocardial perfusion.

Albumins↗
PubMed2002

Influence of microbubble shell properties on ultrasound signal: Implications for low-power perfusion imaging.

Low mechanical index perfusion imaging relies on the detection of signals produced by microbubble oscillation at low acoustic powers that results in minimal microbubble destruction. We hypothesized that the optimal acoustic power for real-time imaging would differ for microbubbles with different shell characteristics. Three microbubble agents with varying shell elastic properties according to their polymer composition were studied. Differences in the elastic properties of these microbubbles was demonstrated by: (1) measurement of their bulk modulus and (2) evaluation of their acoustic lability by microscopic visualization of microbubble destruction during insonification at incremental acoustic powers. The ultrasound signal generated by these microbubbles at various mechanical indexes and the degree of microbubble destruction during continuous imaging was determined both in an in vitro flow system and during in vivo imaging in an open-chest canine model. Both studies indicated that optimal power for achieving maximal signal intensity with minimal microbubble destruction was influenced by the shell elastic properties. We conclude that the acoustic power for maximizing acoustic signal without destroying microbubbles during low mechanical index imaging varies according to shell characteristics.

Acoustics↗
PubMed2003

Microbubble ultrasound contrast in the assessment of hepatic artery patency following liver transplantation: role in reducing frequency of hepatic artery arteriography.

We prospectively evaluated the role of microbubble ultrasound contrast for detection of hepatic artery thrombosis following liver transplantation. The hepatic artery of adult liver transplant recipients with suspected thrombosis on surveillance Doppler ultrasound (US) were re-examined by a second observer. In patients with no hepatic spectral Doppler signal the microbubble contrast agent Levovist was used. The presence or absence of flow following microbubble contrast was evaluated against arteriography or repeated Doppler US findings. A total of 794 surveillance Doppler US examinations were performed in 231 patients. Hepatic artery flow was demonstrated in 759 of 794 (95.6%) examinations. Microbubble ultrasound contrast was administered in 31 patients (35 studies) with suspected hepatic artery thrombosis. Following microbubble US contrast the hepatic artery could not be demonstrated in 13 of 35 (37.1%) studies (12 patients). Eight patients had arteriography: there was hepatic artery thrombosis in 7 patients and 1 patient had a patent, highly attenuated artery. Detection of a patent hepatic artery increased from 759 of 794 (95.6%) to 781 of 794 (98.4%) with the addition of microbubble contrast. Upon independent reading of the data, the degree of operator confidence in the assessment of the hepatic artery patency prior to microbubble contrast was 4.7 (CI 1.92-7.5) but rose to 8.45 (CI 7.06-9.84) following microbubble contrast ( p<0.0001). In 22 of 35 (62.9%) of studies arteriography could potentially have been avoided. Ultrasound microbubble contrast media may reduce the need for invasive arteriography in the assessment of suspected hepatic artery thrombosis.

Adult↗
PubMed2006

Enhanced gene delivery into skeletal muscles with ultrasound and microbubble techniques.

RATIONALE AND OBJECTIVES: This experiment was directed to explore the effects of ultrasound microbubbles on gene structure in vitro and green fluorescent protein (GFP) plasmid transfer into skeletal muscles in vivo. By establishing a rat ischemic hind limb model, the effects of ultrasound-mediated microbubble destruction on vascular endothelial growth factor (VEGF) gene transfection to skeletal muscles were also studied in vivo. MATERIALS AND METHODS: Ultrasound irradiation was applied on the mixture of microbubbles and GFP plasmid in vitro. Gel electrophoresis was used to detect the effects of ultrasound and microbubbles on GFP plasmid. For in vivo experiments, ultrasound irradiation was applied on the hind limb after directly injecting microbubbles into the hind limb of Wistar rats. Directly after treatment, the skeletal muscles were harvested to observe the microstructure. We also studied the transfer rate of GFP plasmid DNA into the skeletal muscles of rats by applying ultrasound and microbubble technique. Furthermore, a naked VEGF plasmid was applied to study the feasibility of angiogenesis by using rats ischemia models. RESULTS: Gel electrophoresis of plasmid DNA showed that there was no difference between the groups. By studying the hematoxylin and eosin stained pictures of the skeletal muscles, we found that ultrasound irradiation of skeletal muscle after injection of microbubbles could cause the exudation of the red blood cells, whereas it had no effects on the microstructure of muscle fibers. In vivo experiments showed that an ultrasound microbubble could enhance the transfer of plasmid DNA to the skeletal muscles. CONCLUSIONS: The ultrasound-mediated microbubble technique provides an effective noninvasive method for gene therapy.

Animals↗
PubMed2005

Microbubbles during radiofrequency catheter ablation: composition and formation.

OBJECTIVES: The purpose of this study was to measure tissue temperatures associated with microbubble formation during radiofrequency (RF) ablation. BACKGROUND: Microbubble formation visualized by echocardiography has been used to indicate excessive tissue heating during RF pulmonary vein isolation. However, little is known about the tissue temperatures associated with microbubble formation. METHODS: Optical fluorometric thermometry probes were used to record tissue temperatures in isolated porcine atrium overlying either lung or esophageal tissue in a saline bath. RF energy was delivered through an irrigated ablation electrode during echocardiographic monitoring for microbubble formation. RESULTS: The maximal recorded tissue temperatures were 81.0 +/- 5.0 degrees C and 88.3 +/- 8.1 degrees C at the time of intermittent (type 1) microbubble formation for lung and esophageal preparations, respectively. During continuous (type 2) microbubble formation, the temperatures were 91.4 +/- 8.2 degrees C and 99.2 +/- 7.8 degrees C, respectively (both P < .001 vs type 1). Tissue temperatures averaged >100 degrees C at the time of "pops." The maximal recorded temperature occurred up to 4 mm deep in the tissues and frequently occurred external to the atrial tissue. The total RF lesion volumes for lung and esophageal preparations were related to the pattern of microbubble formation but not to total power delivered. After generation of type 1 bubbles, up to 60% reductions in RF energy were needed to restore target tissue temperatures of 65 degrees C. Gas chromatographic analysis of the microbubbles was consistent with steam formation. CONCLUSIONS: Microbubble formation during RF ablation represents excessive tissue heating to the point of steam formation. Maximal tissue heating may occur in the adjacent lung and esophagus during cooled ablation.

Animals↗
PubMed2006

Optimal design and experimental investigation of surfactant encapsulated microbubbles.

The diagnostic capabilities of ultrasound imaging can be improved with contrast-specific nonlinear imaging modalities such as harmonic and subharmonic imaging. The nonlinear response of an encapsulated microbubble in an acoustic field is strongly influenced by the shell viscoelastic properties that are determined by the shell composition and thickness. In this paper, the subharmonic performance of a surfactant encapsulated microbubble was optimized by choosing the appropriate composition of shell material with the aid of theoretical model. To study the effects of viscoelastic properties of microbubble shell materials on the nonlinear scattered response of microbubbles, a theoretical model-modified Herring equation for the oscillation of encapsulated microbubbles in the ultrasound field was employed. Based on this model, a computer aided design system was developed to optimize and analyze the acoustic properties, particularly subharmonic responses, of microbubbles under different shell parameters. Furthermore, surfactant encapsulated microbubbles with different viscoelastic properties were prepared by changing the shell composition. Their shell viscoelastic behavior was measured indirectly as dilational modulus of monolayer film formed with surfactant molecular. Moreover, in vitro quantitative acoustic properties measurements of these microbubbles were carried out to evaluate their subharmonic performance. Both of the theoretical simulation and acoustic measurement showed that the surfactant encapsulated microbubbles with good subharmonic properties could be designed and prepared by adjusting the shell material composition with the guide of the computer aided design system.

Capsules↗