SEARCH · PubMed Health

Results for “Microbubbles”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,783 records · Page 99Linked to original sources

PubMed2005

Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation.

High-intensity focused ultrasound (US), or HIFU, treatment of soft tissues has been shown to result in a hyperechoic region in B-mode US images. We report on detecting cavitation in vivo in correlation with the appearance of a hyperechoic region. The US system consisted of a HIFU transducer (3.3 MHz), a broadband A-mode transducer for active and passive cavitation detection and an US-imaging probe that were all confocal and synchronized. HIFU, at in situ intensities of 220 to 1710 W/cm(2), was applied for 10 s to pig muscles in vivo. Active and passive cavitation detection results showed a strong correlation between the onset of cavitation and the appearance of a hyperechoic region. Passive cavitation detection results showed that inertial cavitation typically occurred prior (within 0.5 s) to the appearance of a hyperechoic region. The observed cavitation activity confirms that bubbles are present during the formation of a hyperechoic region at the HIFU focus.

Acoustics↗

PubMed2005

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.

Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

Albumins↗

PubMed2006

Pulsed cavitational ultrasound therapy for controlled tissue homogenization.

Methods were investigated to acoustically control the extent to which cavitation-mediated tissue homogenization is responsible for lesion formation in vitro. These results may guide potential therapeutic procedures that induce damage predominantly via mechanical disruption and, thereby, avoid limitations associated with thermal ablative modalities. Porcine myocardium was insonified at 750 kHz using pulse sequences consisting of high-amplitude pulses (22 MPa Pr) interleaved with variable-amplitude "sustaining" pulses (e.g., 6.9 MPa Pr), which were intended to provide sufficient acoustic input to maintain cavitation activity between primary pulses, but to increase the spatial peak temporal average intensity (I(SPTA)) only marginally. Using modest temporal-average intensities (e.g., I(SPTA) approximately 200 W/cm2), approximately 0.5 cm3 lesions were produced consisting of homogenate that could be irrigated away to reveal smooth cavities. The prevalence of homogenate in a given lesion was sensitive to both pulse-repetition frequency and sustaining pulse amplitude, suggesting the existence of optimum acoustic parameters for producing homogenized lesions largely via mechanical perturbation.

Animals↗

PubMed2006

Disposition of perfluorobutane in rats after intravenous injection of Sonazoid.

The new ultrasound contrast agent Sonazoid was injected IV in rats at doses of 0.8 and 8 muL perfluorobutane (PFB)-containing microbubbles/kg body weight. Samples were obtained from blood, liver, spleen, fat, kidney, muscle, heart, lung and brain from both males and females and the PFB gas was analyzed using validated gas chromatography mass spectrometry methods. No differences were observed between genders or doses for any of the pharmacokinetic parameters. For all tissues, the highest concentrations were observed at the first time point (i.e., 5 min postinjection) (51% of injected dose in liver; total recovery of 69%). The highest concentrations of PFB in tissue were observed in spleen > liver > lung > kidney >> other tissues. At 24 h after dosing, the total amount of PFB remaining in the tissues was 1.9%. These data fit well with the finding that after a Sonazoid dose of 8 microL microbubbles/kg to male rats, more than 50% of the injected PFB was recovered in exhaled air by 20 min after dosing. During the first 24 h after administration, more than 96% of the PFB dose was recovered in exhaled air.

Animals↗

PubMed2006

Inertial cavitation dose produced in ex vivo rabbit ear arteries with Optison by 1-MHz pulsed ultrasound.

Previous in vitro studies have shown that ultrasound-induced mechanical bioeffects with contrast agents present are highly correlated with inertial cavitation (IC) "dose" (Chen et al. 2003a, 2003c). The ex vivo experiments conducted here addressed the following hypotheses: 1. IC activity can be generated by insonating perfused rabbit ear blood vessel, and 2. the IC "dose" developed during insonation treatment can be reliably measured and will vary with varying acoustic parameters and Optison concentration. Ex vivo rabbit auricular arteries were perfused with Optison suspensions and then exposed to 1.1-MHz pulsed focused ultrasound. Experimental variables included peak negative acoustic pressure (0.2 MPa to 5.2 MPa), pulse-repetition frequency (5, 50 or 500 Hz), pulse length (50, 100, 500 or 1000 cycles), and Optison volume concentration (0, 0.2, 0.5 or 1%). Cavitation activity was quantified as IC dose, based on passive cavitation detection measurements. The results show that: 1. The IC pressure threshold decreases with higher concentrations of Optison, and 2. IC dose increases significantly with increasing acoustic pressure, Optison concentration, pulse length or with decreasing pulse-repetition frequency.

Albumins↗

PubMed2006

Application of liposomes to sonoporation.

A method to prepare liposomes is presented. Liposomes made in our laboratory were characterized acoustically and optically. The phase velocity and attenuation of liposomes in suspension (concentration = 10(9)/mL) were measured, ranging from 2 to 14 MHz, using ultrasound spectroscopy. Anti-rabbit IgG conjugated with Alexafluor 647 was delivered into Jurkat cells in suspension, using the liposomes, by 10 % duty cycle ultrasound tonebursts of 2.2 MHz (the in situ spatial peak-pressure amplitude = 80 W/cm2) with an efficiency of 13 %. It has been experimentally shown that liposomes may be an alternative stable agent to Optison for delivering macromolecules into cells.

Albumins↗

PubMed2006

Histopathological observations of the antivascular effects of physiotherapy ultrasound on a murine neoplasm.

This study evaluates the histopathological changes that follow insonation of a neoplasm with physiotherapy ultrasound. In 27 mice (C3HV/HeN strain), a subcutaneous melanoma (K1735(22)) was insonated with continuous physiotherapy ultrasound (1 MHz; spatial-average-temporal-average = 2.3 W cm(-2)). Analyses of contrast enhanced (0.1 mL Optison) power Doppler observations showed that insonation significantly (p < 0.05) increased the avascular area in the neoplasm. The predominant acute effect of insonating the neoplasm was an apparently irreparable dilation of the tumor capillaries with associated intercellular oedema; other immediate effects were haemorrage and increased intercellular fluid. Liquefactive necrosis of neoplastic cells was a delayed effect. There was a high correlation (R2 = 0.91) between the percent area affected on histologic examination and the percent increase in avascularity of the neoplasm in the Doppler study. In conclusion, physiotherapy ultrasound produced histologic changes in the tumor vasculature that were consistent with observations made by contrast enhanced power Doppler ultrasound.

Albumins↗

PubMed2006

Nonlinear intravascular ultrasound contrast imaging.

Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is investigated using a prototype IVUS system and an experimental small bubble contrast agent. The IVUS system employed a mechanically scanned single element transducer and was operated at a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). Characterization experiments were performed with agent and tissue phantom signals acquired during transducer rotation. The suppression of transmit frequency tissue signals was achieved using a combination of pulse-inversion and bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals suppressed to near the noise floor. Coronary phantom experiments demonstrated the detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel in which the IVUS catheter was situated. These results suggest the feasibility of harmonic IVUS contrast imaging, which may have applications in coronary lumen boundary detection and vasa vasorum imaging.

Blood Vessels↗

PubMed2006

High frequency nonlinear scattering from a micrometer to submicrometer sized lipid encapsulated contrast agent.

An experimental lipid encapsulated contrast agent comprised substantially of micrometer to submicrometer diameter bubbles was evaluated for its capacity to produce nonlinear scattering in response to high transmit frequencies. Agent characterization experiments were conducted at transmit frequencies of 20 and 30 MHz with bandwidths of 5, 15 and 25% using a broadband focused PVDF transducer. The presence of subharmonic energy was observed for all bandwidths at a wide range of pressures (0.49 to 5.7 MPa and 0.45 to 4.5 MPa for the 20 and 30 MHz cases, respectively). Distinct ultraharmonics were observed only in the 5% bandwidth cases. Second harmonic energy was also present, but this was at least partly due to nonlinear propagation, as indicated by linear scatterer signals. Evidence of destruction was found only at higher peak negative pressures (e.g., >2 MPa for 30 MHz 5% bandwidth pulse). The results suggest that small lipid bubble formulations may be useful for the purposes of high frequency nonlinear contrast imaging.

Acoustics↗

PubMed2006

Ultrasonographic portography with low mechanical index gray-scale imaging in hepatic VX2 tumor.

To evaluate the characteristics of portal blood supply of hepatic tumors by ultrasonographic portography (USP), an in vivo model was studied using SonoVue, a second-generation ultrasound contrast agent (UCA) and low mechanical index (MI), gray-scale harmonic imaging. SonoVue (0.05 mL) was administrated through catheter placed into the main trunk of portal vein at laparotomy, followed by a 0.5 mL saline flush, in 12 rabbits with hepatic VX2 tumor, implanted by VX2 tumor tissue cubes of approximately 1 mm3 from carrier rabbit. Results showed that low MI gray-scale imaging delineated clearly the dynamic enhancement of tumors and liver parenchyma. Among 22 tumors, seven tumors were diffusely increased, with the intensity of enhancement weaker than that of the surrounding liver parenchyma. The UCA was washed out earlier from tumors than from surrounding liver parenchyma. Three tumors showed the branches of portal vein. Five tumors showed peripheral contrast enhancement and a central coarse unenhanced hypoechoic area. Seven tumors displayed no actual enhancement. All lesions (100% [22 of 22]) were depicted clearly in the whole duration of enhancement, especially in the early and late phase, regardless of enhancement pattern, and portal blood flow was manifested in 15 of 22 (68%) tumors, by USP. The enhancement pattern of the tumors corresponded to the pathologic findings. The results indicated that ultrasonographic portography, combined with low MI levels and second-generation UCA, is a sensitive and safe method to study portal blood supply for liver cancer. It may contribute to improvement of the detectability and diagnostic ability and assist the choice of a therapeutic strategy for treatment of liver cancer. However, applicability of the method to human may be problematic because of high invasiveness and great difficulty in administering contrast medium.

Animals↗

PubMed2006

3D perfusion mapping in post-infarct mice using myocardial contrast echocardiography.

Myocardial contrast echocardiography (MCE) was used to construct three-dimensional maps of perfusion defects in closed-chest mice, with and without myocardial infarction (MI) induced by permanent coronary ligation. Contiguous, short-axis MCE cine images spanning the heart from apex to base were acquired at 1 mm elevations in each mouse. MCE images at each elevation were color-coded to indicate relative perfusion and were compared with postmortem histology. A strong correlation (R > 0.93) in the size of perfused areas was observed between in vivo measurements and the results of conventional ex vivo tissue staining. 3D multislice and 3D surface renderings of perfusion distribution were created and these perfusion maps also matched well with postmortem histology. These methods provide for the noninvasive determination of the total ischemic region placed at risk by coronary occlusion: this is a critical variable in assessing the potential of novel therapeutic agents to reduce MI size in murine models of ischemia/reperfusion injury.

Animals↗

PubMed2006

Numerical analysis of a gas bubble near bio-materials in an ultrasound field.

Ultrasonic cavitation bubble phenomena play a key role in numerous medical procedures such as ultrasound-assisted lipoplasty, phacoemulsification, lithotripsy, brain tumor surgery, muscle and bone therapies and intraocular or transdermal drug delivery. This study investigates numerically the interaction of a bubble with a bio-material (fat, skin, cornea, brain, muscle, cartilage or bone) involved in the treatments mentioned when subjected to an ultrasound field. A range of frequencies is used to study the bubble behavior in terms of its growth and collapse shapes, and the maximum jet velocity attained. Simulation results show complex dynamic behaviors of the bubble. In several cases a jet is formed directed away from the bio-material while in others, toward it. In certain cases, the bubble eventually breaks into two, with or without the formation of opposite penetrating jets. Very high maximum velocities of jets directing away or toward the bio-materials can be observed in some cases (700 to 900 ms(-1)).

Gases↗

PubMed2006

Measurement and correlation of acoustic cavitation with cellular bioeffects.

Using broadband noise as a measure of cavitation activity, this study determined the kinetics of cavitation during sonication of Optison contrast agent and tested whether cellular bioeffects can be predicted by cavitation dose. Cell suspensions were exposed to ultrasound at varying acoustic frequency, pressure, exposure time, Optison concentration and cell type to obtain a broad range of bioeffects, i.e., intracellular uptake and loss of viability, as quantified by flow cytometry. We found that cavitation activity measured by broadband noise increased and peaked within 20 ms and then decayed with a half-life of tens to hundreds of milliseconds. Intracellular uptake and loss of viability correlated well with the cavitation dose determined by the time integral of broadband noise magnitude. These results demonstrate that broadband noise correlates with bioeffects over a broad range of experimental conditions, which suggests a noninvasive feedback method to control ultrasound's bioeffects in real time.

Albumins↗

PubMed2006

Biological and physical mechanisms of HIFU-induced hyperecho in ultrasound images.

Guidance and monitoring of high intensity focused ultrasound (HIFU) therapy, using ultrasound imaging, has primarily utilized formation of a hyperechoic region at the HIFU focus. We investigated biologic and physical mechanisms of a hyperecho, as well as safety of this phenomenon, using thermal, acoustic and light microscopy observations. Single, short-duration HIFU pulses (30-60 ms) were able to produce a hyperechoic region at the HIFU focus, 2 cm deep in a rabbit thigh muscle. When hyperechoic regions appeared, inertial cavitation was detected in vivo using a custom-made passive cavitation detection system. Light micrographs showed a large number of cavities (approximately 100/mm3), 1-10 microm in diameter, in a cytoplasm of cells located at the HIFU focus. Blood congestion was observed around a focal region, indicating an injury of microvasculature. Cellular necrosis was observed at 2 d after the treatment, while healing, scar tissue formation and regeneration were observed at 7 d and 14 d. The results indicate that a possibility of adverse tissue effects has to be taken into consideration when the hyperecho formation, induced by very-short HIFU pulses, is used for pretreatment targeting.

Acoustics↗

PubMed2006

Interactions between consecutive sonications for characterizing the thermal mechanism in focused ultrasound therapy.

The use of focused ultrasound for thermal ablation or therapy has become a promising modality due to its high selectivity and noninvasiveness. The temperature increase that induces thermal necrosis in the focal beam area has been reported to be attributed to the absorption of ultrasound energy and heating enhancement by acoustic cavitation. The purpose of this study is to propose a novel experimental arrangement to observe the thermal lesion formation and to demonstrate that the presence of the ultrasound-induced, macroscopically-visible bubbles may exert a key effect in thermal lesion formation. In our experiments, consecutive sonications with orthogonal intersections were applied to observe the thermal lesion interaction induced by 577- or 1155-kHz ultrasound. Results showed that the 1155-kHz heating was dominated by ultrasound energy absorption, with blocking of consecutive sonications being evident only rarely. However, in 577-kHz sonications, the thermal process was dominated by inertial cavitation and the corresponding ultrasound-induced, macroscopically-visible bubbles, which was verified from the later lesion being blocked by the former one and direct observation from light microscopy. This study demonstrates that the operating frequency for ultrasound thermal ablation should be selected based on the intended specific thermal mechanisms to be induced.

Humans↗

PubMed2006

Refill model of rabbit kidney vasculature.

A refill model previously developed in flow phantoms was modified to simulate the refill of cortical and medullary rabbit kidney tissues. The highly structured kidney tissues were accounted for by considering refill both within and across the scan-plane. Refill curves were acquired with ultrasound contrast from rabbit kidneys using high MI disruption pulses followed by low MI real-time imaging. The comparison of the real medullary and cortical tissues with their corresponding models resulted in an RMS error of 11% and 18%, respectively, indicating that simple assumptions about a tissue's vascular structure are predictive of refill behaviour. Tissue classification images were generated using the refill models and an exponential simplification. These images were indistinguishable and matched what is expected of a kidney, indicating that the primary distinguishing characteristic between kidney tissue types is mean transit time. However, the vascular model is useful in predicting and explaining tissue properties that affect refill behavior.

Animals↗

PubMed2006

Ultrasound, contrast agents and biological cells; a simplified model for their interaction during in vitro experiments.

A model based on simplifying assumptions is described for the time course of an in vitro experiment in which a beam of ultrasound passes through a suspension of biological cells and gaseous contrast agents (UCAs). It is assumed that cavitation-related activation events (AEs) occur, during each of which a UCA is destroyed or becomes nonfunctional and, at the same time, nearby cells are lysed or otherwise altered. If the UCAs are highly concentrated, the ultrasound attenuation is high and may significantly affect the action. The number of cells affected by each AE depends on the concentrations of cells and UCAs as well as the concentration ratio.

Animals↗

PubMed2006

Contrast-enhanced ultrasound (CEUS) for the study of peripheral lung lesions: a preliminary study.

The use of contrast-enhanced ultrasound (CEUS) for the study of peripheral lung lesions has never been systematically investigated. We evaluated the CEUS patterns of 98 peripheral lung lesions before performing US-guided fine-needle biopsies (FNB). The examinations were done with an Esaote Technos MPX scanner in the harmonic mode with a mechanical index of 0.04 or less. Contrast enhancement was achieved with a 4.8 mL bolus of SonoVue (Bracco) administered via an antecubital vein. All FNBs performed under CEUS guidance were adequate for pathologic diagnosis. Seventy-eight lesions were malignant: 33 (41.9%) were adenocarcinomas, 29 (36.5%) were squamous-cell carcinomas, 13 (17.6%) were undifferentiated large-cell carcinomas and the remaining three (4.1%) were small-cell carcinomas. All presented intralesional enhancement consistent with tumor neovascularization. In some cases, there were unenhanced areas consistent with zones of necrosis and these areas were avoided during FNB. The other 20 lesions were benign (four lipomas, two fibrous lung tumor, two noncaseous granulomas, six abscesses, one rheumatoid nodule, one histiocytosis X, one chondroid hamartoma, one sclerosing hemangioma, two sarcoid nodules) and none presented intralesional enhancement. This initial and admittedly limited experience suggests that CEUS may provide diagnostically useful information on peripheral lung lesions and increase the diagnostic yield of transthoracic FNB by reducing the risk of inadequate tissue sampling.

Adenocarcinoma↗