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PubMed1984

Microbubbles have intracardiac velocities similar to those of red blood cells.

The slope of an individual contrast trajectory on M-mode echocardiography represents the projection of the intracardiac velocity vector of a microbubble in the direction of the sound beam. Doppler echocardiography measures this projection of red blood cell velocity. To ascertain whether microbubbles have similar intracardiac velocities to those of red blood cells, 11 subjects were studied during intravenous injections of 5% dextrose solution. The flow across the tricuspid and pulmonary valves was examined. Microbubble velocity was measured by M-mode contrast slope analysis and simultaneously by Doppler technique. Results from both methods were correlated with red blood cell velocity measured by Doppler recording at the same time in the cardiac cycle, shortly before appearance of contrast medium (3 to 8 beats before the corresponding contrast velocity measurements). In all subjects, 10 sets of three velocities each (M-mode slope and Doppler data before and during contrast injection) were obtained for each valve. Visual inspection of the Doppler tracings showed similar velocity profiles before and during contrast appearance; the signal intensity was greater with contrast. Quantitatively, microbubble velocity assessed by M-mode trajectory slopes correlated well with the Doppler-derived velocity of red blood cells (r = 0.98, p less than 0.001, slope of the regression line = 0.99, standard error of the estimate = 7 cm/s). Doppler velocities measured with and without contrast medium showed a similar correlation (r = 0.99, p less than 0.001, slope of regression = 1.01, standard error of the estimate = 6 cm/s). In individual subjects, the correlation coefficient between microbubble and red blood cell velocities ranged form 0.978 to 0.998.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Air-filled proteinaceous microbubbles: synthesis of an echo-contrast agent.

Air-filled microbubbles are in clinical use as echo-contrast agents for sonographic applications. The synthesis of aqueous suspensions of air-filled proteinaceous microbubbles involves the ultrasonic irradiation of aqueous protein solutions in the presence of O2. Yields and size distributions of human and bovine serum albumin microbubbles have been determined as a function of various experimental parameters. The chemical nature of these microbubbles and the origin of their remarkably long lifetimes have been explored. The microbubbles are held together primarily by interprotein cross-linking of cysteine residues. The principal cross-linking agent is superoxide created by the extremely high temperatures produced during acoustic cavitation.

Animals↗
PubMed2003

Prediction of respiratory distress syndrome by the microbubble stability test on gastric aspirates in newborns of less than 32 weeks' gestation.

AIM: There is a need for a rapid method to identify infants who will develop respiratory distress syndrome (RDS) soon after birth, to allow early treatment of affected infants with surfactant. The microbubble stability test (MST) may be one such method, but clinical experience is sparse. METHODS: The MST was performed on gastric aspirates from 188 infants with a mean gestational age of 29 (range 23-31) wk. RESULTS: 87 infants developed moderate to severe RDS, corresponding to a prevalence of 46%. The sensitivity, specificity and predictive values for identification of infants with moderate to severe RDS were determined for the average diameter of bubbles, the proportion of microbubbles with different diameters and the total number of microbubbles. The proportion of microbubbles with diameters <20 or 25 microm gave the best prediction, with a sensitivity of 78-79%, a specificity of 57-58%, a positive predictive value of 62% and a negative predictive value of 76%. Early treatment with nasal continuous positive airway pressure probably mitigated the development of RDS in some infants with a low-degree surfactant deficiency and this may explain the relatively low specificity. CONCLUSION: In infants of <32 wk gestation RDS can be predicted by computerized image analysis of the size distribution of microbubbles generated in gastric aspirates.

Gestational Age↗
PubMed2005

Different effects of microbubble destruction and translation in Doppler measurements.

In flow measurements in which microbubbles are involved, the amplitude and phase of the received echo signal are noticeably influenced by the transmitted ultrasound intensity. Previous studies have shown that, when such intensity is progressively increased, the Doppler spectrum is accordingly distorted, i.e., it is asymmetrically broadened toward the negative frequency side. Such deformation has been attributed to radiation force, which pushes the microbubbles into the sound propagation direction, thus yielding additional phase delays in the received echoes. However, the possible contribution of microbubble destruction to this spectral deformation has not been considered yet. In this paper, this issue is investigated by analyzing the experimental spectra produced by two different types of microbubbles suspended in a moving fluid and insonified in pulsed wave (PW) mode at programmable pulse repetition frequency (PRF) and pressure. Conditions are created in which either the radiation force or the destruction mechanism is expected to be dominant. Effects produced by the two phenomena on the Doppler spectrum are shown to be different. When the PRF is low (2 kHz), so that, according to theoretical simulations, the radiation force effect is negligible, a 26 dB noise floor increase is observed for a 13 dB pressure increment. For a higher PRF (16 kHz), the same pressure increase not only affects the noise floor, but also causes the bubbles to deviate from their original streamlines, yielding a Doppler bandwidth increase by a factor of 5. It is concluded that asymmetrical spectral broadening is mainly due to radiation force, and microbubble destruction mainly results in an increased noise floor without affecting the spectral shape.

Algorithms↗
PubMed2005

Prediction of the ablated area by the spread of microbubbles during radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND/AIM: Radiofrequency ablation (RFA) is effective for the treatment of hepatocellular carcinoma (HCC). To prevent the ablation of adjacent organs and vessels, the spread of microbubbles generated by heating during RFA was observed by ultrasonography (US) and used to predict the ablated area; however, several reports documented that discrepancies existed between the spread of microbubbles and the ablated area. PATIENTS AND METHODS: The spread of microbubbles during RFA was observed by US in 24 patients with HCC and the areas were compared with the defect of enhancement in contrast enhanced (CE)-US, using Levovist in the same plane. RESULTS: During the ablation, the posterior margin was obscure but the border could be visualized 5 min after the ablation. The size of the area of hyperechogenicity 5 min after ablation and that of the defect observed by CE-US was found to correlate (r(2)=0.91, P<0.0001). The shape of the hyperechogenicity corresponded well to the defect area, even in cases showing irregular spread of the microbubbles. CONCLUSION: The observation of microbubbles during RFA can predict the ablated area and might be useful to prevent the unfavorable ablation of adjacent organs and vessels.

Adult↗
PubMed1991

Lipid-coated uniform microbubbles for earlier sonographic detection of brain tumors.

Rapid technological improvements have fostered the continued clinical development of intraoperative neurosonology, despite the fact that no suitable contrast media have been available for ultrasound studies. Because they can be made of uniform size (99% are less than 4.5 mum in diameter) and are thought to cross disruptions in the tumor vessels, artificial lipid-coated microbubbles can fill this gap. Furthermore, these microbubbles are stable in vitro for at least 6 months, with an in vivo halflife of 20 hours or more. This study demonstrated that lipid-coated microbubbles injected intravascularly can intensify echoes from rat brain gliomas. Specifically, when this standardized microbubble contrast agent was injected intravenously daily in rats, the time to visual ultrasonic detection of developing brain tumors (C-6 gliomas) was 4.09 days (n = 11) after tumor inoculation, versus 6.67 days (n = 9) to detection without microbubble injection (Z = -3.71, p = 0.0004).

Air↗
PubMedDate not supplied

A physical model describing the mechanism for formation of gas microbubbles in patients with mitral mechanical heart valves.

This study was aimed at developing a physical model, supported by experimental observations, to describe the formation and growth of microbubbles seen in patients with mitral mechanical heart valves (MHV). This phenomenon, often referred to as high intensity transient signals (HITS), appears as bright, intense, high-velocity and persistent echoes detected by Doppler ultrasonography at the instant of closure. The long-term clinical implications of HITS has yet to be determined. However, there are reports of a certain degree of neurological disorder in patients with mitral MHV. The numerical analysis has shown the existence of a twofold process (1) nucleation and (2) microbubble growth as a result of cavitation. While mild growth of nuclei is governed by diffusion, explosive growth of microbubbles is controlled by pressure drop on the atrial side of mitral MHV. It was demonstrated that there exist limits on both microbubble size and regurgitant velocity, above which microbubbles grow explosively, and below which growth is almost nonexistent. Therefore, prevention of excessive pressure drops induced by high closing velocities related to the dynamics of closure of mitral MHV may offer design changes in the future generations of mechanical valves.

Blood Pressure↗
PubMed2004

Spectral normalization for ultrasonic contrast microbubble detection.

Ultrasonic contrast agents consisting of microbubbles are used to assess tissue perfusion. The microbubbles are highly reflective and nonlinear and thus produce harmonics that are stronger than those from tissues. However, the magnitude of harmonic signals resulting from a region with microbubbles also depends on the acoustic pressure of incident ultrasound and the attenuation of intervening tissues in the ultrasound path. Therefore, the harmonic magnitude, as used in traditional harmonic imaging, may not be a reliable indicator of the presence or absence of microbubbles, and hence, tissue perfusion. To compensate for these effects, we present two parameters defined as the ratio of the harmonic to the fundamental component (HFR) and the ratio of the harmonic to squared fundamental (HSFR). A simplified model is used to illustrate the usefulness of these two parameters. Experiments show that both parameters improve detection of microbubbles and that HSFR performs better than HFR.

Contrast Media↗
PubMed2001

Significant reduction of air microbubbles with the dynamic bubble trap during cardiopulmonary bypass.

Air microbubbles mostly occur unnoticed during cardiopulmonary bypass and are predominantly responsible for serious postoperative psychoneurological dysfunction. A dynamic bubble trap (DBT), which removes air microbubbles from the arterial blood, was tested in a clinical study. The aim was to evaluate the efficiency of microbubble removal under clinical conditions. As blood passes through the DBT, which is placed in the arterial line between the arterial filter and arterial cannula, it is converted into a rotating stream. The bubbles are directed to the centre of the blood flow and are collected in the distal end of the DBT, from where they are returned to the cardiotomy reservoir. Doppler ultrasonography was used to detect the microbubbles before and after the DBT, and also the number of high-intensity transient signals (HITS) in the right and left middle cerebral artery during extracorporeal circulation. A significant reduction of microbubbles in the arterial line (3,990 before DBT, 537 after, p < 0.001) and HITS in the brain (51 in the DBT group, 77 in the placebo group, p = 0.04) was measured.

Adult↗
PubMed1996

Surfactant protein A and stable microbubble formation in tracheal aspirates.

This study aimed to determine the role of surfactant protein A (SP-A) in the formation of stable microbubble in tracheal aspirates. Our results showed that as the concentration of anti SP-A antibodies added to tracheal aspirate specimens increased, the number of stable microbubble formed in the specimen decreased. The correlation between stable microbubble counts and the SP-A levels in the tracheal aspirates was good, r = 0.85, p < 0.05. This study suggests that SP-A plays an important role in stable microbubble formation. Measurement of small stable microbubbles is thus a useful bedside test for predicting the SP-A activity in the tracheal aspirates and in indirect measurement of lung maturity.

Animals↗
PubMed2000

A dynamic bubble trap reduces microbubbles during cardiopulmonary bypass: a case study.

Microemboli passing to the cerebral circulation during cardiopulmonary bypass can contribute to postoperative neurologic dysfunction. Many studies conclude that air microbubbles predominantly are responsible for this problem. A dynamic bubble trap (DBT) was developed to diminish the number of microbubbles in the arterial line of extracorporeal circulation. The DBT is able to substantially reduce the number of air microbubbles, as shown in two patients undergoing coronary artery bypass grafting, where a high number of microbubbles was assessed. Although a 40-micron arterial filter was used, many bubbles larger than 40 microns occurred in the arterial line. The DBT reduced the number of large microbubbles from 2,267 to 67 in patient 1 and from 897 to 61 in patient 2.

Aged↗
PubMed2002

Hepatic artery stenosis following liver transplantation: significance of the tardus parvus waveform and the role of microbubble contrast media in the detection of a focal stenosis.

PURPOSE: To evaluate the role of microbubble ultrasound contrast media in detecting stenosis of the post-liver transplant extrahepatic hepatic artery (HA) in the presence of the tardus parvus spectral Doppler waveform of the intrahepatic HA. MATERIALS AND METHODS: All post-liver transplant patients with a prolonged systolic acceleration time (SAT>0.08s) and/or a reduced resistant index (RI<0.50) of the HA (the tardus parvus waveform) on colour Doppler ultrasound (CDUS), were assessed with microbubble contrast medium for a focal arterial stenosis. Following microbubble contrast-enhanced CDUS, patients underwent arteriography or follow-up CDUS. RESULTS: A total of 2038 examinations were performed in 529 liver transplant recipients; 16 (3.02%) tardus parvus waveforms were identified. The median SAT of the intrahepatic HA was 0.18s (range 0.11-0.38s) and the RI 0.47 (range 0.22-0.58). No extrahepatic elevated peak systolic velocity (PSV), defined as above 1.00m/s, was detected on the baseline examinations. Following the administration of microbubble contrast, medium, PSV in the extrahepatic HA was elevated in 14 of 16 patients, (median=2.15m/s, range=1.44-3.10m/s); flow was not identified in two patients. Arteriography was performed in 10 patients and confirmed stenosis in eight (median grade of stenosis 93%, range 60-99%) and occlusion in two. The measured median PSV at contrast-enhanced CDUS in the stenosis group was 2.03m/sec (range 1.44-2.71m/sec). Repeat CDUS in six patients not undergoing arteriography showed resolution in four; one underwent re-transplantation before arteriography and one patient maintains a tardus parvus waveform. In transplant recipients undergoing arteriography during the study period (n=55), no hepatic artery stenosis without a tardus parvus waveform was seen. CONCLUSION: The tardus parvus waveform pattern is an excellent screening test for the presence of post-liver transplantation hepatic artery stenosis. There is only a limited role for microbubble ultrasound contrast agent in the presence of a tardus parvus waveform. It could be used following equivocal colour Doppler ultrasound, but arteriography will still be necessary.

Adolescent↗
PubMed1991

Microbubble damage to the blood-brain barrier: relevance to decompression sickness.

Decompression sickness affecting the nervous system is still a serious problem in diving, but the mechanisms involved are in dispute. Although microbubbles can be detected in the pulmonary artery on decompression using ultrasound, mammalian lungs are competent filters for microbubbles larger than 20 microns in diameter. It has been assumed that smaller bubbles released by the lungs are harmless, because there is evidence that they do not arrest in the cerebral circulation. We injected 15 +/- 5 microns diameter microbubbles in 5 ml of plasma slowly into the right carotid artery of anesthetized guinea pigs. At intervals of 1, 2, or 3 h postinjection, 2% trypan blue in 2 ml of plasma was injected into the same artery or the contralateral carotid artery. A control animal for each experiment was injected with 5 ml of plasma only, followed by the injection of dye at the same interval. After the animals were killed, the brains were examined for evidence of blood-brain barrier dysfunction. All animals at 1 h, and 9 out of 10 animals at 2 h after the injection of microbubbles, showed extravasation of the albumin-binding dye in the ipsilateral hemisphere, indicating gross blood-brain barrier dysfunction. In each of the matched controls, the barrier in the neocortex remained intact. At Hour 3 the barrier was impermeable to the trypan blue in both experimental and control animals. These experiments demonstrate that microbubbles impair the blood-brain barrier integrity to protein, causing focal edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Induction of platelet aggregation in vitro by microbubbles of nitrogen.

Microbubbles of nitrogen gas act as a platelet agonist, but the biochemical mechanisms involved in bubble-induced platelet activation are not well known. One characteristic property of a platelet agonist is to potentiate the response by another agonist in a synergistic manner at low concentrations. Possible synergism between N2 gas bubbles and the physiologic agonists ADP, epinephrine, and 5-hydroxytryptamine (5-HT) was tested. The interaction with ADP was additive; N2 microbubbles and ADP had different aggregation profiles, and the bubbles made the reversible ADP aggregation irreversible. Epinephrine caused a strong, synergistic stimulation of bubble-induced platelet aggregation. This synergism was only partially inhibited by indomethacin and acetylsalicylic acid, but abolished by yohimbine. 5-HT had an inhibitory effect on N2 microbubble-induced platelet aggregation. This effect was neutralized by the S2-serotonergic receptor blocker ketanserin. Microbubble stimulation of the platelets before stimulation with ADP, epinephrine, and 5-HT seemed to make them more sensitive to epinephrine only. The strong synergism between microbubbles and epinephrine in vitro should be evaluated for possible future use in predive selection of divers.

Adenosine Diphosphate↗
PubMed1995

[Relationship between retained microbubbles and neuropsychologic alterations after cardiac operation].

We studied the relationship between quantity of microbubble retained in the left heart and neuropsychologic alterations after surgery in 21 patients undergoing cardiac surgery including cardiopulmonary bypass. The neuropsychologic change was evaluated by three kinds of psychological test, which mainly analyzed memory and cognition. The microbubble was continuously monitored by the long axis view of the descending aorta of transesophageal echocardiography and then quantitatively analyzed and graded by the on-line computer. More microbubbles were detected in the valve surgery requiring the intracardiac procedure than in coronary artery bypass grafting and neuropsychologic deterioration, although the relationship did not reach statistical significance. Since most of the microbubbles were detected during the unclamping of aorta and the weaning from cardiopulmonary bypass, a technical improvement of the surgical procedures could reduce them. We think that transesophageal echocardiography is useful for monitoring microbubbles during operation.

Adult↗
PubMed1998

[Properties of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect].

The property of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect of abdominal organs on gray scale ultrasound are here described. The size of microbubbles of CO2 gas adequately prepared with 5% human serum albumin was nearly 23 microns in mean diameter. However, the size and the density of gas microbubbles are affected with many factors, including mixing times, volume ratio of gas and liquid and the species of gas and liquid. On the other hand, contrast enhancing effect is determined by the size and the density of gas microbubbles. For the adequate evaluation of contrast enhancing effect of abdominal tumors by enhanced ultrasonography, the property of gas microbubbles described as above should be carefully considered.

Abdomen↗
PubMed2003

Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals.

Ultrasonography has, until recently, lacked effective contrast-enhancing agents. Micrometer-sized gas bubbles that resonate at a diagnostic frequency are ideal reflectors for ultrasound. However, simple air bubbles, when injected into the blood stream, disappear within seconds through the combined effects of Laplace pressure, blood pressure, and exposure to ultrasound energy. Use of fluorocarbon vapor, by extending the persistence of microbubbles in vivo from seconds to minutes, propelled contrast ultrasonography into clinical practice. Imaging techniques that selectively suppress tissue, but not microbubble signal, further increase image contrast. Approved products consist of C3F8 or SF6 microbubbles, and N2 microbubbles osmotically stabilized with C6F14. These agents allow the detection and characterization of cardiovascular abnormalities and solid organ lesions, such as tumors. By providing higher quality images, they improve the accuracy and confidence of disease diagnosis, and can play a decisive role in clinical decision making. New objectives include agents that target specific cells for the molecular imaging of disease, and drug and gene delivery, including ultrasound-triggered delivery.

Cardiovascular Diseases↗
PubMed2005

Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound microbubbles.

BACKGROUND: Although gene therapy might become a promising approach to treat spinal cord injury, the safety issue is a serious consideration in human gene therapy. Plasmid DNA transfer is safer than viral vectors, but the transfection efficiency is quite low. To overcome the problem, we applied the ultrasound microbubbles-mediated transfection method to the spinal cord in adult rats, since ultrasound microbubbles have been reported to be efficient to increase transfection efficiency in various tissues. METHODS: After exposing T9-10 spinal cord with a laminectomy, we injected a mixture of naked plasmid DNA and microbubbles into cerebrospinal fluid by lumbar puncture. Then, the T9-10 spinal cord was exposed to ultrasound. CONCLUSIONS: An ultrasound intensity of 0.4-0.5 W/cm2 significantly increased luciferase expression up to approximately 15-60-fold at the insonated level as compared to naked plasmid DNA alone. Luciferase activity could be detected at least up to 7 days after transfection, while the expression level was almost returned to undetectable level at 14 days after transfection. The transfected cells were mainly meningeal cells in the surface of insonated spinal cord. There was no obvious evidence of worsening of neurological deficits as compared to rats transfected with naked plasmid DNA alone or untransfected rats. Similarly, successful gene transfer was also achieved in the insonated T9-10 spinal cord after spinal cord injury. Overall, the present study demonstrated the feasibility of ultrasound microbubbles-mediated plasmid DNA transfer into the target level of the spinal cord.

Animals↗