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Results for “Microbubbles”

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PubMed1997

Detection of myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles using transient response second harmonic imaging.

OBJECTIVES: The purpose of this study was to prove that transient response harmonic imaging could detect normal and abnormal myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles in humans. BACKGROUND: Myocardial ultrasound contrast can be produced from intravenous perfluorocarbon-exposed sonicated dextrose albumin, and ultrasound can be significantly improved by briefly suspending the interval between frame rates. Whether this contrast can noninvasively quantify myocardial perfusion in humans is unknown. METHODS: In 28 patients, harmonic transient response imaging was used to image the heart in multiple different imaging planes after one intravenous injection of ultrasound contrast agent. Twenty-five of these 28 patients had a repeat injection during dipyridamole stress. In the primary view, the ultrasound transmission rate was one frame per cardiac cycle; in secondary and tertiary views, the transmission rate was once every multiple cardiac cycles. Regional myocardial contrast was visually assessed and quantified off-line. Quantitative rest thallium and dipyridamole stress sestamibi imaging was also performed. RESULTS: Perfusion abnormalities were evident in the secondary and tertiary views only with one frame every multiple cardiac cycles. Regional peak myocardial videointensity (PMVI) correlated closely with regional tracer uptake in individual patients both at rest (r = 0.84) and during stress (r = 0.88). A PMVI ratio (abnormal region divided by the region with highest nuclear uptake) < 0.6 in any view had a 92% sensitivity and a 84% specificity in identifying a regional nuclear perfusion abnormality. CONCLUSIONS: Transient response imaging produces myocardial contrast in multiple views with one intravenous injection of contrast agent and can accurately identify regional myocardial perfusion abnormalities.

Adult↗

PubMed2000

Microbubble-enhanced ultrasound for vascular gene delivery.

Progress in cardiovascular gene therapy has been hampered by concerns over the safety and practicality of viral vectors and the inefficiency of current nonviral transfection techniques. We have previously reported that ultrasound exposure (USE) enhances transgene expression in vascular cells by up to 10-fold after naked DNA transfection, and enhances lipofection by up to three-fold. We report here that performing USE in the presence of microbubble echocontrast agents enhances acoustic cavitation and is associated with approximately 300-fold increments in transgene expression after naked DNA transfections. This approach also enhances by four-fold the efficiency of polyplex transfection, yielding transgene expression levels approximately 3000-fold higher than after naked DNA alone. These data indicate an important role for acoustic cavitation in the effects of USE. Ultrasound can be focused upon almost any organ and hence this approach holds promise as a means to deliver targeted gene therapy in cardiovascular conditions such as such angioplasty restenosis and in many other clinical situations.

Albumins↗

PubMed2002

Microbubble-endothelial cell interactions as a basis for assessing endothelial function.

Clinical signs and symptoms of coronary artery disease are predated in decades by endothelial dysfunction, an aberration in the vascular lining that permits the development and propagation of atherosclerotic lesions and vasomotor dysfunction in the arterial circulation. These ultimately lead to acute and chronic coronary ischemic syndromes. Other pathophysiologic scenarios encountered in clinical cardiology practice, such as cardiac transplant rejection and the period following coronary angioplasty or cardiac surgery, also are associated with endothelial dysfunction. Endothelial dysfunction parallels coronary risk factors and is potentially reversible, rendering early identification of the phenomenon a clinically important endpoint. Current methods for detecting endothelial dysfunction are limited, however. Myocardial contrast echocardiography using microbubbles targeted to bind to cell surface markers uniquely expressed by dysfunctional endothelial cells may offer an approach to the noninvasive detection of endothelial disease using clinical ultrasound imaging techniques. This article will discuss the concept of targeted ultrasound imaging and present preliminary studies in this area as applied to endothelial assessment. Potential applications to other disease states, both diagnostic and therapeutic, also are discussed.

Contrast Media↗

PubMed2002

Spontaneous echocardiographic microbubbles associated with prosthetic mitral valves: mechanistic insights from thrombolytic treatment results.

The purpose of this study was to determine the prevalence of microbubbles (MBs) in patients with prosthetic mitral valves (PMVs). The clinical and echocardiographic predictors of MB were investigated. We also analyzed the temporal relation between MBs and the thrombolytic treatment of thrombotic PMV dysfunction. The study material comprised 307 transesophageal echocardiography examinations in 279 patients (170 women and 109 men with a mean age of 37.9 +/- 13.3 years) with PMV. The PMV was mechanical in 245 patients (tilting-disk valves in 129, and bileaflet aortic valves in 116) and bioprosthetic mitral valves in 34 patients. Twenty-eight sessions of thrombolytic treatment were performed because of the obstructive (n = 18) and nonobstructive (n = 10) thrombi involving the PMV. No MBs were seen in any of the bioprosthetic valves. The MBs were present in 128 of 227 (56.4%) PMV without obstruction compared with only 1 of 18 (5.5%) valves with thrombotic obstruction (P <.0001). The MB were documented in 75.4% of the normal bileaflet valves compared with 38.5% of the tilting-disk valves (P <.0001). The MB intensity score was also significantly higher in the bileaflet valves (2.0 +/- 0.8 vs 0.7 +/- 0.7, P <.05). The incidence of MBs increased from 5.5% to 68.7% after successful thrombolysis in patients with obstructive PMV thrombi (P <.001). There were no other predictors of MBs in this series. The passage of MBs in the aortic root was not documented in any instances. We conclude that MBs are normal echocardiographic findings depending on the type and function of the mechanical PMVs.

Adult↗

PubMed1998

In vivo magnetic resonance vascular imaging using laser-polarized 3He microbubbles.

Laser-polarized gases (3He and 129Xe) are currently being used in magnetic resonance imaging as strong signal sources that can be safely introduced into the lung. Recently, researchers have been investigating other tissues using 129Xe. These studies use xenon dissolved in a carrier such as lipid vesicles or blood. Since helium is much less soluble than xenon in these materials, 3He has been used exclusively for imaging air spaces. However, considering that the signal of 3He is more than 10 times greater than that of 129Xe for presently attainable polarization levels, this work has focused on generating a method to introduce 3He into the vascular system. We addressed the low solubility issue by producing suspensions of 3He microbubbles. Here, we provide the first vascular images obtained with laser-polarized 3He. The potential increase in signal and absence of background should allow this technique to produce high-resolution angiographic images. In addition, quantitative measurements of blood flow velocity and tissue perfusion will be feasible.

Angiography↗

PubMed2004

An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system.

Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity.

Acoustics↗

PubMed1999

Pulmonary transit of sonicated albumin microbubbles during controlled mechanical ventilation: a transthoracic echocardiographic study.

UNLABELLED: Air-filled human serum albumin microspheres are ultrasonic contrast tracers that pass through the right ventricle, traverse the lungs, and effectively opacify the left heart chambers in spontaneously breathing patients. In this clinical study, we assessed whether they also do so in anesthetized patients during and after mechanical ventilation. In 20 anesthetized patients undergoing intermittent positive pressure ventilation (IPPV) for elective peripheral neurosurgical procedures, a sonicated ultrasound contrast drug (0.06 mL/kg) was injected i.v. before inducing anesthesia in spontaneously breathing patients (baseline), during IPPV, and 5 and 30 min after tracheal extubation. Transthoracic echocardiograms were obtained in the four-chamber apical view and were recorded for off-line analysis. Time to contrast appearance in the right ventricle and pulmonary transit time were measured in cardiac cycles. The peak intensity of right and left ventricular chamber opacification were scored on a scale ranging from 1 (no contrast or traces only) to 5 (attenuation). After each injection, the time for contrast appearance in the right ventricle was similar in all patients. Pulmonary transit time increased significantly during IPPV and was normal 5 min and 30 min after extubation. Right ventricular chamber opacification achieved high-grade intensity and remained constant before, during, and after IPPV. Conversely, although the baseline contrast injection resulted in high-grade left ventricular chamber opacification, the intensity decreased significantly during IPPV, remained low 5 min after extubation, and was normalized 30 min after extubation. IMPLICATIONS: During intermittent positive pressure ventilation, i.v. sonicated albumin microbubbles pass through the lungs poorly and inefficiently opacify the left ventricle compared with the effects observed during spontaneous ventilation.

Anesthesia, General↗

PubMed1995

BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles.

RATIONALE AND OBJECTIVES: The basic characteristics of BR1, a novel echo contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles have been evaluated. METHODS: The authors determined the physicochemical properties (bubble concentration, bubble size distribution, resistance to pressure, and stability) and the acoustic properties (backscatter and attenuation coefficients) of BR1. The diagnostic value of BR1 was evaluated further in minipigs. Left heart images were recorded before and after injection of different doses of BR1. RESULTS: BR1 is formulated as a lyophilized product, which after addition of saline, provides a suspension containing 2 x 10(8) SF6 microbubbles/mL with a number mean diameter of 2.5 microns. More than 90% of the bubbles are below 8 microns. The use of SF6 rather than air provides an improved resistance to pressure increases such as the ones occuring in the left heart during systole. After reconstitution, the echogenicity and the bubble characteristics are unchanged for more than 8 hours. The high echogenicity remains almost constant over the entire medical frequency range (1-10 MHz). BR1 injections in animals resulted in a homogenous, dose-dependent opacification of the left heart. CONCLUSIONS: Considering its high echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a very promising ultrasound contrast agent.

Animals↗

PubMed1997

Evaluation of effect of treatment for invasive bladder cancer by ultrasonography with intra-arterial infusion of carbon dioxide microbubbles.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the diagnostic usefulness of the ultrasonography with intra-arterial infusion of carbon dioxide microbubbles (CO2) for invasive bladder cancer. METHODS: Twelve patients with muscle-invading bladder cancer who were treated by concurrent radiotherapy and intra-arterial infusion of daily low dose of cisplatin using an implanted infusion port were included. A total of 30 studies was performed during the treatment to evaluate the visualization of the tumor and effect of the treatment compared with conventional ultrasonography, computed tomography, or cystoscopy. RESULTS: Satisfactory visualization of the tumor in CO2 ultrasonography was obtained in all patients, in particular in those with flat tumor or prostatic invasion. The enhancement effect of CO2 on the tumor, which was maintained well in the late period of the treatment, made possible evaluation of the therapeutic effect. With respect to the evaluation of local response, disagreement between clinical response and the evaluation of CO2 ultrasonography was observed in two patients with definite differentiation between wall edema and residual tumor after treatment being difficult. CONCLUSIONS: Carbon dioxide ultrasonography is easy to perform in patients treated with arterial infusion therapy using an implanted infusion port and provides practical information in evaluating therapeutic effect.

Aged↗

PubMed1997

Evaluation of lipid-coated microbubbles as a delivery vehicle for Taxol in brain tumor therapy.

OBJECTIVE: This work evaluates the potential of lipid-coated microbubbles (LCM) as a delivery vehicle for lipid-soluble antineoplastic agents. We have shown, in rats, the selective affinity of intravenously administered LCM for tumor cells. They are internalized by the tumor cells both in vitro and in vivo. The specificity of LCM for tumors and subsequent incorporation into the cytoplasm could significantly reduce the systemic effects of an agent incorporated into the bubbles, such as Taxol. METHODS: The in vitro methods were as follows. C6 cells (10(5) cells) were treated with Taxol-LCM (6 micrograms/ml), Taxol-Cremophore (6 micrograms/ml), or LCM alone for 8 or 24 hours. Cell death was determined by staining the cells with nuclear staining. Abnormalities of microtubule structures were ascertained by confocal microscopy. The in vivo methods were as follows. Two rat tumor models (C6 and 9L) were used. Rats were treated with single bolus injections or with repetitive (two or three) treatment courses, with respective control animals. Each course consisted of one daily tail vein injection for 5 consecutive days and then 2 days of rest. RESULTS: When compared with either a saline control group or a group receiving Taxol in an oil vehicle, Taxol-LCM reduced tumor progression in Fischer 344 rats inoculated with 9L glioma. The most profound effect was observed with rats treated with three treatment cycles (five daily injections/cycle) separated by two rest periods (2 d/period). CONCLUSION: Both in vitro and in vivo data indicate that Taxol can be incorporated into LCM, can be delivered to the tumor site, and can exert a measurable antitumor biological effect.

Animals↗

PubMed1998

The use of lipid-coated microbubbles as a delivery agent of 7beta-hydroxycholesterol in a radiofrequency lesion in the rat brain.

OBJECTIVE: This laboratory has previously described the aggregation of intravenously administered lipid-coated microbubbles (LCM) around tumors and areas of injury. 7Beta-hydroxycholesterol has been used to inhibit astrocytic proliferation in nervous system injury models. The compound has been given by direct infusion, by epidural catheter, or in liposomes (delivered stereotactically to the injury site). In this article, we report the use of LCM to deliver 7beta-hydroxycholesterol to a radiofrequency injury site in the rat cerebrum. METHODS: First, the ability of LCM to target the thermal lesion in the rat brain was characterized using a lipid-soluble fluorescent dye 3,3-dioctadecyloxacarbocyanine perchlorate. Then, the effectiveness of this delivery system in suppression of glial proliferation was measured by glial fibrillary acidic protein immunoreactivity. RESULTS: Glial fibrillary acidic protein immunoreactivity was significantly reduced when 7beta-hydroxycholesterol was administered via LCM but not alone, suggesting that astrocytic proliferation would correspondingly be diminished. CONCLUSION: LCM were assessed as a delivery vehicle for 7beta-hydroxycholesterol in a rat brain radiofrequency lesion and found to be efficient in reducing astrogliosis, as measured by glial fibrillary acidic protein immunoreactivity.

Animals↗

PubMed1999

The affinity of lipid-coated microbubbles to maturing spinal cord injury sites.

OBJECTIVE: This laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion to the upper thoracic region. METHODS: The accumulation of LCMs in the injured spinal cord was analyzed by labeling it with a lipid-soluble fluorescent dye, 3,3'-dioctadecyloxacarbocyanine perchlorate. Indices of glial fibrillary acidic protein were measured concomitantly with 3,3'-dioctadecyloxacarbocyanine perchlorate-labeled LCMs using confocal microscopy. RESULTS: There was no aggregation of LCMs accumulated 1 and 6 hours after injury; however, when given 2, 4, and 7 days after injury, LCMs showed a clear affinity for the injured region. LCM aggregation shifted from the central necrotic area of the injury on postinjury Day 2 and postinjury Day 4 to the white matter among glial fibrillary acidic protein-positive astrocytes by postinjury Day 7. CONCLUSION: Affinity of LCMs for spinal cord injury sites may be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by glial fibrillary acidic protein-positive astrocytes in adjacent white matter. These findings suggest a potential for using LCMs as a delivery vehicle to concentrate lipid-soluble agents in spinal cord injury sites.

Animals↗

PubMed2003

Inhibition of renal fibrosis by gene transfer of inducible Smad7 using ultrasound-microbubble system in rat UUO model.

TGF-beta is a key mediator in renal fibrosis. Kidney-targeted gene therapy with anti-TGF-beta strategies is expected to have therapeutic potential, but this has been hampered by concerns over the safety and practicability of viral vectors and the inefficiency of nonviral transfection techniques. The present study explored the potential role of TGF-beta/Smad signaling in renal fibrosis in vivo and developed a safe and effective gene therapy to specifically block TGF-beta signaling and renal fibrosis in a rat unilateral ureteral obstruction (UUO) model by transferring a doxycycline-regulated Smad7 gene or control empty vectors using an ultrasound-microbubble (Optison)-mediated system. The Smad7 transgene expression was tightly controlled by addition of doxycycline in the daily drinking water. Groups of six rats were sacrificed at day 7, and the transfection rate, Smad7 transgene expression, and tubulointerstitial fibrosis including alpha-smooth muscle actin and collagen matrix mRNA and protein expression were determined. Compared with the non-ultrasound treatment, the combination of ultrasound with Optison largely increased the transfection rate of FITC-ODN and Smad7 transgene expression up to a 1000-fold, and this was found in all kidney tissues. Compared with normal rats, Smad7 expression within the UUO kidney was significantly reduced, and this was associated with up to a sixfold increase in Smad2 and Smad3 activation and severe tubulointerstitial fibrosis. In contrast, treatment with inducible Smad7 resulted in a fivefold increase in Smad7 expression with complete inhibition of Smad2 and Smad3 activation and tubulointerstitial fibrosis in terms of tubulointerstitial myofibroblast accumulation (85% downward arrow ) and collagen I and III mRNA and protein expression (60 to 70% downward arrow ). In conclusion, the ultrasound-mediated inducible Smad7 gene transfer is a safe, effective, and controllable gene therapy. TGF-beta-mediated renal fibrosis is regulated positively by Smad2/3, but negatively by Smad7. Target blockade of TGF-beta/Smad signaling by expression of Smad7 may provide a new therapeutic potential for renal fibrosis.

Air↗

PubMed2003

Observation of laser-pulse-induced traveling microbubbles in dusty plasma liquids.

We report a direct experimental observation of traveling microbubbles induced by intense laser pulses in strongly coupled dusty plasma liquids. The dense plasma ablated from a suspended dust particle generates a spherical plasma bubble with a low dust density, in the quiescent regime before a transition to self-organized longitudinal dust density waves. It travels downwards at a velocity about 6 cm/sec inside the dust liquid. Dust density fluctuations trailing the bubble are also observed. The bubble generated in the high pressure dissipative regime collapses right after formation.

Journal Article↗

PubMed1997

Stimulated Acoustic Emission Nonbackscatter Contrast Effect of Microbubbles Seen with Harmonic Power Doppler Imaging.

Transient imaging has been introduced to enhance the signal intensities when using echo contrast agents. However, this phenomenon is not clearly understood. To evaluate the mechanisms of this phenomenon, isolated pig hearts were investigated with different echo imaging techniques in the beating, working heart as well as in an asystolic state without any motion of the heart. The hearts of five German farm pigs (21 +/- 2.5 kg) were surgically explanted and inserted in an artificial circulation providing physiological flow and pressures. Levovist in the dosage of 0.05-0.3 g was injected into the left atrium and contrast effects evaluated in the left ventricular (LV) cavity and in the myocardium with an ultrasound imager (ATL, HDI 3000) equipped with a prototype software for harmonic imaging. Harmonic B-scans and power Doppler registrations were performed with continuous and intermittent recordings (ECG triggered at end-systole) in the beating heart and using an external trigger in the asystolic heart in which perfusion was interrupted for 20 seconds. In the beating pig heart, transient harmonic power Doppler imaging provided intensive opacification of the LV cavity and visible myocardial uptake when ECG triggering was performed. In the asystolic pig heart, with uninterrupted perfusion, both triggered and nontriggered registrations showed contrast signals in the LV cavity and in the myocardium. These findings cannot be explained with the known physics of ultrasound contrast media. Stimulated acoustic emission occurring during disintegration of the microbubbles in the acoustic field would explain this phenomenon, which has not yet been described for Levovist.

Journal Article↗

PubMed1991

Air microbubbles as a contrast medium in transcranial Doppler sonography. A pilot study.

An insufficient signal-to-noise ratio is a significant limiting factor in assessing intracranial hemodynamic parameters by transcranial Doppler sonography. To establish the feasibility and validity of signal enhancement in transcranial Doppler sonography, stabilized air microbubbles bound to galactose microparticles as a carrier (SHU 454) were used in an animal model. The disadvantage of a short-lasting effect is caused by instability of the contrast medium and a consequent reduced capacity to pass through the lung. Eight pigs received SHU 454 intraarterially in various concentrations and forms of application during transcranial monitoring of the middle cerebral artery with a 2 MHz pulsed ultrasound device. The effect was reproducible, dependent on the dose and application modalities. The best results were obtained with low concentrations (100 mg of microparticles/ml of suspension) and low injection speeds (0.5-1.0 ml/sec) into the common carotid artery by injection pump, reaching a homogeneous average enhancement of 6 to 12 dB over at least 5 minutes. Histological examination of the brain showed no evidence of air embolization. Further development requires a stable solution with similar properties and an ability to pass through the lung, therefore being suitable for intravenous application in humans.

Air↗

PubMedDate not supplied

Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells.

Microsecond laser pulses are currently being investigated in a new ophthalmic procedure for treatment of disorders associated with the retinal pigment epithelium (RPE). The precise mechanism for microsecond laser-induced RPE damage, however, has not been determined. We have previously shown that short pulse laser irradiation in the nanosecond to picosecond time domain causes transient microbubble formation around melanin granules in pigmented cells. Nanosecond time-resolved microscopy was previously used to visualize the intracellular cavitation dynamics. However, this technique is difficult to use with microsecond laser exposures, especially when multiple laser pulses are applied in a rapid sequence as in the clinical setting. Here we describe a simple pump-probe method for detecting transient light scattering signal from individual RPE cells when they are irradiated with nanosecond and microsecond laser pulses. For single 12 ns pulses the threshold for bubble detection was the same as the ED(50) threshold for cell death. For 6 micros pulse duration the threshold for bubble detection was about 10% higher than the threshold for cell death. With repetitive pulse trains at 500 Hz the ED(50) decreased about 25% for 10 and 100 pulses. Cells die when a single bubble was detected in a multiple pulse sequence.

Air↗

PubMed1998

Magnetic resonance imaging of microbubbles in a superheated emulsion chamber for brachytherapy dosimetry.

This paper describes development of magnetic resonance imaging (MRI) techniques for three-dimensional (3D) imaging of a position-sensitive detector for brachytherapy dosimetry. The detector is a 0.5 l chamber containing an emulsion of halocarbon-115 droplets in a tissue-equivalent glycerin-based gel. The halocarbon droplets are highly superheated and expand into vapor microbubbles upon irradiation. Brachytherapy sources can be inserted into the superheated emulsion chamber to create distributions of bubbles. Three-dimensional MRI of the chamber is then performed. A 3D gradient-echo technique was optimized for spatial resolution and contrast between bubbles and gel. Susceptibility gradients at the interfaces between bubbles and gel are exploited to enhance contrast so microscopic bubbles can be imaged using relatively large voxel sizes. Three-dimensional gradient-echo images are obtained with an isotropic resolution of 300 microns over a 77 mm x 77 mm x 9.6 mm field-of-view in an imaging time of 14 min. A post-processing technique was developed to semi-automatically segment the bubbles from the images and to assess dose distributions based on the measured bubble densities. Relative dose distributions are computed from MR images for a 125I brachytherapy source and the results compare favorably to relative radial dose distributions calculated as recommended by Task Group 43 of the American Association of Physicists in Medicine.

Algorithms↗