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At least 451 records · Page 25Linked to original sources
PubMed1993

Microbubble image enhancement and pericardiocentesis.

When performing pericardiocentesis, if blood-stained fluid is aspirated, one must ensure that the aspirating needle is not within one of the cardiac chambers. To clarify the position of the needle some contrast material may be injected using X-ray screening and for this reason pericardiocentesis is often performed in the catheter laboratory, particularly if the effusion is small, loculated or the heart is in an unusual position. Ultrasound immaging is now commonly used to guide the aspirating needle and if blood-stained fluid is withdrawn we reinject a few millilitres and this outlines the space from which the fluid is withdrawn with microbubbles. This modification of ultrasound immaging adds to the safety of the procedure and allows difficult procedures to be carried out in the ward or intensive care unit, where X-rays screening is not easily available.

Adolescent↗
PubMed1993

Applications of lipid-coated microbubble ultrasonic contrast to tumor therapy.

Lipid-coated microbubbles (LCM) make an excellent diagnostic ultrasonic contrast agent in experimental tumor systems. LCM have been shown to aggregate in brain tumors and subcutaneous tumors after intravenous administration, and to provide persistent image enhancement for many minutes. In this work, experimental subcutaneous Walker Carcinosarcoma is insonated after the bubbles are given intravenously. Selective necrosis, lymphocyte proliferation and hemorrhage within the tumor can be demonstrated. Preliminary data are given to demonstrate this phenomenon. The mechanism of the effect is discussed in the context of both heating and cavitation.

Animals↗
PubMed2005

Sonoporation using microbubble BR14 promotes pDNA/siRNA transduction to murine heart.

Naked plasmid DNA (pDNA) and short interfering RNA (siRNA) duplexes were transduced into adult murine heart by means of sonoporation using the third-generation microbubble, BR14. Plasmid DNAs carrying luciferase, beta-galactosidase (beta-gal), or enhanced green fluorescent protein (EGFP) reporter genes were mixed with BR14 and injected percutaneously into the left ventricular (LV) cavity of C57BL/6 mice while exposed to transthoracic ultrasound at 1MHz for 60s. Sonoporation at an output intensity of 2.0W/cm(2) and a 50% pulse duty ratio resulted in the highest luciferase expression in the heart. Histological examinations revealed significant expression of the beta-gal and EGFP reporters in the subendocardial myocardium of LV. Intraventricular co-injection of siRNA-GFP and BR14 with concomitant ultrasonic exposure resulted in substantial reduction in EGFP expression in the coronary artery in EGFP transgenic mice. The present method may be applicable to gain-of-function and loss-of-function genetic engineering in vivo of adult murine heart.

Animals↗
PubMed2004

The potential for thermal damage posed by microbubble ultrasound contrast agents.

The development of coated microbubble ultrasound contrast agents for use in imaging applications and as carriers in drug and gene delivery applications has intensified the need for a clear understanding of their behaviour and potential bioeffects. Previous studies have focused on the risks posed by unencapsulated bubbles as representing the "worst case scenario". They have concluded that the risk of thermal damage should be minimal provided the threshold for inertial cavitation is not exceeded. However, these treatments have ignored the heating effects due to viscous dissipation in the coatings of contrast agent particles. Simulations indicate that the temperature rise due to this process may be sufficient to generate harmful bioeffects even under conventionally "safe" insonation conditions. The implications of these findings and strategies for addressing the risks posed by contrast agents are discussed.

Contrast Media↗
PubMed2004

A numerical investigation of the resonance of gas-filled microbubbles: resonance dependence on acoustic pressure amplitude.

The general Keller-Herring equation for free gas bubbles is augmented by specific terms to describe the elasticity, viscosity and thickness of the encapsulating shell in ultrasound contrast agent microbubbles. A numerical investigation that analyses the acoustic backscatter from bubbles is employed to identify resonance frequencies that can be compared, for increasing driving pressure amplitude, with linear approximations obtained via analytical considerations. Calculations for bubbles of the size employed in diagnostic ultrasound, between 2 and 6 mum diameter, that are immersed in water and blood and exposed to monochromatic insonation, causing the bubbles to undergo stable cavitation, reveal that the resonance frequency diverges from the linear approximation as the pressure amplitude is increased. The shift in resonance, to lower frequency values, is found to be more pronounced for larger bubbles with the calculated value differing by up to 40% from the linear approximation. The results of this simulation might be potentially useful in preparation of formulations of ultrasound contrast agents with the specifically desired features, such as for instance resonance frequency.

Journal Article↗
PubMed1998

The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction.

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.

Aged↗
PubMed1998

Use of microbubble ultrasound contrast agent to demonstrate the iris valve effect in human eye bank eyes.

PURPOSE: To demonstrate that the interface between the normal iris and the lens surface functions as a flap valve. METHOD: Microbubble ultrasound contrast agent was injected into the anterior and posterior chambers of human eye bank eyes and the distribution of contrast imaged with high-frequency ultrasound. RESULTS: Contrast agent did not enter the posterior chamber when injected into the anterior chamber, but contrast agent injected into the posterior chamber easily flowed into the anterior chamber. CONCLUSIONS: The iris-lens interface normally functions as a flap valve, preventing retrograde flow from the anterior to the posterior chamber. A temporary increase in anterior chamber pressure thus results in iris concavity in pigmentary dispersion syndrome.

Adult↗
PubMed2005

Ultrasound-microbubble-mediated gene transfer of inducible Smad7 blocks transforming growth factor-beta signaling and fibrosis in rat remnant kidney.

Transforming growth factor (TGF)-beta1 has been shown to play a critical role in hypertensive nephropathy. We hypothesized that blocking TGF-beta1 signaling could attenuate renal fibrosis in a rat model of remnant kidney disease. Groups of six rats were subjected to 5/6 nephrectomy and received renal arterial injection of a doxycycline-regulated Smad7 gene or control empty vector using an ultrasound-microbubble-mediated system. Smad7 transgene expression within the kidney was tightly controlled by the addition of doxycycline in the daily drinking water. All animals were euthanized at week 4 for renal functional and histological examination. Hypertension of equivalent magnitude (190 to 200 mmHg) developed in both Smad7- and empty vector-treated rats. However, treatment with Smad7 substantially inhibited Smad2/3 activation and prevented progressive renal injury by inhibiting the rise of 24-hour proteinuria (P < 0.001) and serum creatinine (P < 0.001), preserving creatinine clearance (P < 0.05), and attenuating renal fibrosis and vascular sclerosis such as collagen I and III expression (P < 0.01) and myofibroblast accumulation (P < 0.001). In conclusion, TGF-beta/Smad signaling plays a critical role in renal fibrosis in a rat remnant kidney model. The ability of Smad7 to block Smad2/3 activation and attenuate renal and vascular sclerosis demonstrates that ultrasound-mediated Smad7 gene therapy may be a useful therapeutic strategy for the prevention of renal fibrosis in association with hypertension.

Animals↗
PubMed2003

Potentiation of C-type natriuretic peptide with ultrasound and microbubbles to prevent neointimal formation after vascular injury in rats.

OBJECTIVES: Long-term intravenous infusion of high-dose C-type natriuretic peptide (CNP) is known to prevent neointimal formation after vascular injury. Ultrasound (US) irradiation during microbubbles (MBs) infusion (US/MBs) has been used for local delivery of bioactive agents. We examined whether short-term infusion of CNP could also inhibit neointimal development and whether combined US/MBs treatment at the beginning of the CNP infusion could enhance its effect. METHODS: In the rat carotid artery-balloon injury model, the intima/media area (I/M) ratio 14 days after injury was compared among various short-term post-injury treatments. For combined US/MBs, a commercial echocardiograph (1.8 MHz, mechanical index 1.0) and albumin-coated octafluoropropane gas MBs were used. RESULTS: Infusion of high-dose CNP (1.0 microg/kg/min) immediately after injury for only 24 h successfully reduced the I/M ratio (0.18+/-0.05) to 18% of the ratio in control rats (1.00+/-0.13) that underwent only balloon injury. Although low-dose CNP (0.1 microg/kg/min for 24 h) alone was not effective in reducing the I/M ratio (0.83+/-0.18), combined US/MBs treatment for the first 80 min of the infusion markedly reduced the I/M ratio (0.17+/-0.07), which persisted until 28 days after injury (0.16+/-0.04). CONCLUSIONS: The effects of CNP on the events occurring early after arterial injury may be important in preventing subsequent neointimal development. Thus, intravenous infusion of CNP with US/MBs at its initiation may provide a clinically feasible anti-restenosis therapy applicable immediately after vascular interventions.

Analysis of Variance↗
PubMed2003

Automated quantitative analysis of the shift of frequency spectra generated by attenuated signals from contrast microbubbles.

The ultrasound-induced harmonic microbubble response spectrum is known to shift to lower frequencies with increasing tissue attenuation. We hypothesized that this shift could be reproducibly detected in received broadband radiofrequency spectra. We used an automatic Gaussian curve-fitting technique to measure the mean harmonic response generated by three different contrast agents at six incremental levels of attenuation. Analytical curve fitting identified a consistent, reproducible, and statistically significant shift in mean harmonic frequency with increasing attenuation. The presented method could be a step toward attenuation estimation by contrast harmonic imaging; optimization of harmonic signal reception by ultrasound systems; and, ultimately, automatic detection of contrast agents in tissue.

Acoustics↗
PubMed2000

The acoustics of diagnostic microbubbles: dissipative effects and heat deposition.

We discuss the effectively detectable scattered intensity of ultrasound from diagnostic microbubble suspensions, taking dissipative mechanisms in the liquid medium into account. In particular, we conclude that neither non-linear wave steepening of the incident (driving) wave nor of the outgoing (scattered) wave has a large effect on the scattered signal from typical bubbles. It is shown that, paradoxically, the far-field solution of the wave field is sufficient to compute the magnitude of expected temperature rises in the medium due to acoustic heat deposition, although appreciable heating is limited to intermediate-field distances from the bubble surface.

Acoustics↗
PubMed2000

Bioeffects of positive and negative acoustic pressures in mice infused with microbubbles.

This study provided one test of the hypothesis that hemorrhage in tissues containing ultrasound (US) contrast agents results from inertial cavitation. The test relied on the prediction of classical cavitation theory that the response of microbubbles to negative pressures is much greater than it is for positive pressures. An endoscopic electrohydraulic lithotripter was used to generate a spherically diverging positive pressure pulse. A negative pressure pulse was produced by reflection of the positive pulse from a pressure release interface. Mice were injected with approximately 0. 1 mL of Albunex(R) and exposed to 100 pulses at either + 3.6 MPa or -3.6 MPa pressure amplitude. For comparison, mice were also exposed to the same acoustic fields without injection of contrast agents. Sham animals experienced the same protocols, with or without Albunex(R) injections, but were not exposed to the lithotripter fields. Following exposure, mice were scored for hemorrhage to various organs and tissues. When Albunex(R) was present in the vasculature, negative pressure pulses produced significantly more hemorrhage than positive pressures in tissues such as the kidney, intestine, skin, muscle, fat, mesentery and stomach.

Acoustics↗
PubMed2003

On the destruction of microbubble ultrasound contrast agents.

In recent years, the use of microbubble ultrasound (US) contrast agents as carriers in drug and gene delivery applications has intensified the need for a clear understanding of the processes involved in their destruction. In this study, an analysis of the conditions in the shell of a contrast agent particle has been made, based on the full numerical solution of a modified Rayleigh-Plesset equation. The results indicate that extremely high shell stresses may be expected under typical clinical conditions. Examination of previous experimental evidence in the light of these findings suggests that the shells are almost invariably disrupted, even if they are not visibly destroyed. This has some serious implications, both for targeted delivery processes and reliable assessment of the potential for harmful bioeffects. At present, neither the model nor the experimental data provide an adequate description of contrast agent behaviour. This is due primarily to the lack of information regarding the mechanical response of the shell material and the restriction of the model to the case of small, spherically symmetrical oscillations. Methods for addressing these deficiencies in future work are proposed.

Contrast Media↗
PubMed1999

Effect of acquisition rate on liver and portal vein enhancement with microbubble contrast.

We showed that tissue enhancement with microbubbles is dependent upon transmit power. Because intermittent imaging decreases bubble exposure to ultrasound, and also decreases the ability of the sonographer to maintain anatomic orientation, we aimed to determine the optimum frame rate that maximizes enhancement and allows for continued anatomic orientation. Seven rabbits with an avascular liver lesion created by percutaneous injection of 1 mL ethyl alcohol 7 days earlier were imaged with an Acuson 128XP/10 using a 7-MHz sector transducer at fixed transmit power. Each rabbit was imaged 5 times in random order, at 1 frame/30 s, 1frame/5 s, 1frame/s, 4 frames/s, and 28 frames/s. The same plane was imaged at all frame rates from before to 15 min after the bolus injection of 0.3-mL (0.1-0.12 mL/kg) of AF0150 (Imagent, Alliance Pharmaceutical Corp., San Diego, CA). Liver and portal vein videointensity relative to the lesion were evaluated over time. In this study, liver enhancement progressively increased as the frame rate was reduced (p<0.001). Peak, duration, and area under the time-intensity curve were all greater at the lower frame rates (1 fr/30 s, 1 fr/5 s, and 1 fr/s) than at 28 fr/s (p<0.05). Anatomic orientation was maintained at 1 frame/s rate at which peak enhancement was 44% greater and duration was 100% longer than at 28 frames/s (p<.05). Portal vein enhancement was not affected by frame rate. In conclusion, with intermittent imaging, enhancement was dependent upon frame rate and the ability of the region being imaged to replenish its bubbles between consecutive acquisitions. The 1 frame/s allowed for anatomic orientation and adequate tissue contrast.

Animals↗
PubMed1999

Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles.

The goal of targeted imaging is to produce an enhanced view of physiological processes or pathological tissue components. Contrast agents may improve the specificity of imaging modalities through selective targeting, and this may be particularly significant when using ultrasound (US) to image inflammatory processes or thrombi. One means of selective targeting involves the attachment of contrast agents to the desired site with the use of a specific binding mechanism. Because molecular binding mechanisms are effective over distances on the order of nanometers, targeting effectiveness would be greatly increased if the agent is initially concentrated in a particular region, and if the velocity of the agent is decreased as it passes the potential binding site. Ultrasonic transmission produces a primary radiation force that can manipulate microbubbles with each acoustic pulse. Observations demonstrate that primary radiation force can displace US contrast agents from the center of the streamline to the wall of a 200-microm cellulose vessel in vitro. Here, the effects of radiation force on contrast agents in vivo are presented for the first time. Experimental results demonstrate that radiation force can displace a contrast agent to the wall of a 50-microm blood vessel in the mouse cremaster muscle, can significantly reduce the velocity of flowing contrast agents, and can produce a reversible aggregation. Acoustic radiation force presents a means to localize and concentrate contrast agents near a vessel wall, which may assist the delivery of targeted agents.

Acoustics↗
PubMed2000

Optical imaging of contrast agent microbubbles in an ultrasound field with a 100-MHz camera.

Ultrasound (US) contrast agents, used in the field of medical diagnosis, contain small microbubbles of a mean diameter of about 3 microm. The acoustic behavior of these bubbles in US field has been subject to many investigations. In this study, we propose a method to visualize the behavior of the bubbles in a 0.5-MHz US field under a microscope with a frame rate of 4 MHz. For low acoustic pressures (peak negative pressure of 0.12 MPa), the radius-time curve as measured from the optical images is in agreement with the theory. For higher acoustic pressures (peak negative pressure of 0.6 MPa), the recorded radius is significantly larger than predicted by theory and sudden change in the bubbles shapes has been noticed. The proposed method enables the study and characterization of individual bubbles and their encapsulation. It is expected that this will open new areas for quality control, US contrast imaging and US-guided drug delivery.

Contrast Media↗
PubMed1997

The affinity of lipid-coated microbubbles for maturing brain injury sites.

The availability of a vehicle to deliver lipid soluble agents to a brain injury site may be of potential value in management of brain injury. This work describes the aggregation of intravenously administered Lipid-Coated Microbubbles (LCM) in the injury site following an experimental radiofrequency rat brain lesion. The bubbles can be identified around the region of the injury after the lesion has matured at least 48 h. The greatest bubbles density is evident after the lesion has matured for 10 days. This bubble density, reflecting "affinity," decreases to a plateau level from the second to the third week after injury. In order to investigate the potential relationship of bubble influx to posttraumatic astrocytosis and to cell turnover in the region, we utilized dual-channel laser-scanning confocal microscopy to track both bubble influx into the region and concomitant Glial Fibrillary Acidic Protein (GFAP) expressing astroctyte cell distribution. Cell turnover was assayed in separate sections using immunohistochemical staining of Proliferating Cell Nuclear Antigen (PCNA). We suggest a relationship between the LCM affinity and reactive astrocytes, but found no affinity of LCM for cells which stained positive with PCNA.

Animals↗