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PubMed2002

Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.

OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a microbubble contrast agent. Verification of the diagnosis of a hemangioma was made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n = 5). Ultrasonographic images were obtained before contrast agent administration and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm). Of the 20 hemangiomas, peripheral globular enhancement with progressive centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not be seen, because they were not found on coded harmonic angiographic ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a microbubble contrast agent can depict the typical enhancement pattern in most hepatic hemangiomas.

Contrast Media↗

PubMed2005

Gaseous microemboli and the influence of microporous membrane oxygenators.

Gaseous microemboli (GME) are still an unsolved problem of extracorporeal circuits. They are associated with organ injury during cardiopulmonary bypass. Microbubbles of different sizes and number are generated in the blood as the result of different components of the extracorporeal circuit as well as surgical maneuvers. The aim of our study was to observe the behavior of microporous membrane oxygenators to GME in the daily use and in an in vitro model. For the detection of microbubbles, we used a two-channel ultrasonic bubble counter based on 2-MHz Doppler-System with special ultrasound probes. The amount and size of GME were monitored before and after membrane. In 28 scheduled cases with 3 different oxygenators and variability of surgical procedures, we observed the bubble activity in the extracorporeal circuit. In addition, we used an in-vitro model to study the ability of six different oxygenators by removing air in various tests. The oxygenators tested were manufactured with different membrane technologies. The results of our investigations showed varying membrane design lead to a partial removal of GME as well as a change in size and numbers of microbubbles.

Embolism, Air↗

PubMed1991

New perspectives for perfusion imaging in echocardiography.

The rapid injection into the coronary circulation of solutions containing microbubbles produces an ultrasonic contrast effect in the myocardium. The time-intensity curves generated by sequential videodensitometric analysis of contrast intensity, which is corrected for myocardial background intensity, resembles the curves used in indicator dilution techniques. Studies done in vitro have demonstrated a direct relation between contrast intensity and amount of microbubbles. In animal studies, measurements derived from these curves correlated with changes in myocardial blood flow assessed by microspheres but with varying controversial results. Differences between investigators in technique of injection and size of microbubbles injected are among the list of factors that will alter the time-intensity curve and explain some of the differences in results between investigators. Several factors limit the application of myocardial contrast echocardiography (MCE) to the quantitation of myocardial blood flow. Nevertheless, the results from multiple investigations suggest that the technique is sensitive to changes in perfusion and may be applicable to the evaluation of regional coronary reserve and assessment of the results of revascularization procedures. Peak intensity and area under the time-intensity curve have provided consistent results between investigators; therefore, these measurements have been used to assess regional coronary reserve in experimental studies and patients with coronary artery disease. Although the results are encouraging, they cannot distinguish well between normal and mild impairments in coronary reserve and are subject to larger reproducibility errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Experimental brain abscess: enhanced sonography and pathologic correlation.

A new sonographic contrast agent, gelatin-encapsulated nitrogen microbubbles, was introduced intraarterially to enhance the high-resolution sonographic scan of an experimental brain abscess. The echogenicity produced by the microbubbles correlated closely to the site and distribution of abscess neovascularity. The contrast agent aided in the detection of small necrotic centers in the late stages of abscess evolution when these centers were not visualized on noncontrast sonograms. The echogenic effect of the microbubbles was maximum immediately after injection; it decreased by 5 min and had virtually disappeared at 15 min.

Animals↗

PubMed1995

Patent foramen ovale and hypobaric decompression.

Gas microbubbles were detected in the left ventricle of a supine subject being screened for an atrial septal defect as a participant of a hypobaric decompression study. This determination was made using the saline echocontrast procedure. We found provocation by a Valsalva maneuver not to be necessary in this individual for right-to-left passage of contrast microbubbles into the left heart and middle cerebral artery. When this same individual underwent hypobaric decompression to a simulated altitude of 21,000 ft, numerous gas microbubbles were detected in the right heart, but no gas bubbles were detected in either the left ventricular outflow tract or in the middle cerebral artery. This observation appears to be a novel finding, not previously reported.

Cerebral Arteries↗

PubMed1996

Transcranial high-intensity Doppler signals in patients with mechanical heart valve prostheses: their relationship with abnormal intracavitary echoes.

BACKGROUND AND AIMS OF THE STUDY: In preceding studies, we reported that abnormal Doppler signals of high intensity (HITS) were frequently found in the cerebral arteries of patients with prosthetic mechanical heart valves. These signals should be attributed either to air microbubbles, possibly due to cavitations or to solid emboli elements. On the other hand, the presence of abnormal intracardiac echoes has been reported in patients with mechanical valves. These echoes should be also attributed to air microbubbles or to formed elements. Although in vitro experiments are in favor of the first explanation, the discussion of their origin remains open. METHODS: Among patients subjected to a transesophageal echocardiography (TEE), we selected subjects with mechanical prosthetic heart valves, according to the following criteria: (i) normally functioning valves; (ii) bright echoes suggesting microbubbles, inside the prosthetic valve and/or upstream from it (left ventricular outflow tract or left atrium); (iii) no morphological lesions that could generate solid microemboli at the prosthetic level; (iv) normal carotid arteries, as investigated by color echo-Doppler. RESULTS: Twenty patients were selected: 11 men and nine women of age range 40-64 years. They were implanted with mechanical heart valves (24 Saint-Jude Medical, three Björk-Shiley and one CarboMedics) in the mitral position (10), aortic position (two), or mitral and aortic position (eight) for periods ranging from 10 days to 17 years. There was no major left ventricular dysfunction (mean end-diastolic diameter 51.8 mm; mean ejection fraction 59%). The mean diameter of the left atrium was 46.1 mm. All but three patients were in sinus rhythm; seven had presented with a transient ischemic attack or amaurosis within the six months preceding the investigation. Immediately after TEE, Doppler signals were recorded on the middle cerebral arteries (MCA) during 10 minutes on each side, and the abnormal Doppler signals were counted. Seventeen subjects (85%) exhibited HITS repetition rate from 0.2 to 5.5 per min. CONCLUSION: The percentage of patients with HITS in a non-selected group with mechanical heart valves was about 50%, as observed in previous studies. It appears that in a selected group of patients the percentage with HITS is consistently higher. Therefore, HITS and abnormal intracardiac echoes could have a common origin.

Adult↗

PubMed1998

[Ultrasound contrast agents--newly developed agents and their clinical utility].

Recently many ultrasound contrast agents have been developed. Vascular and parenchymal enhancement of the organs such as liver and myocardium is obtained by intravenous injection of microbubble agents. They can survive after recirculation through the pulmonary capillary beds and under changes in vascular pressure. Several modalities of ultrasound imaging have been developed for effective enhancement. The harmonic imaging system is the most effective to depict contrast enhancement because of subtraction effect using retrieval of harmonic components from interaction microbubbles and ultrasound transmission. This is originated from resonance and destruction of microbubbles under ultrasound exposure.

Contrast Media↗

PubMed2005

Inflammatory low back pain: high negative predictive value of contrast-enhanced color Doppler ultrasound in the detection of inflamed sacroiliac joints.

OBJECTIVE: To determine the value of microbubble contrast agents for color Doppler ultrasound (CDUS) compared with magnetic resonance imaging (MRI) in the detection of active sacroiliitis. METHODS: An observational case-control study of 103 consecutive patients (206 sacroiliac [SI] joints) with inflammatory low back pain according to the Calin criteria and 30 controls (60 SI joints) without low back pain was conducted at the University Hospital of Innsbruck. All patients and controls underwent unenhanced and contrast-enhanced CDUS and MRI of the SI joints. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of unenhanced and contrast-enhanced CDUS were evaluated. RESULTS: Forty-three patients (41%) with 70 of 206 SI joints (34%) and none of the controls nor the 60 control SI joints demonstrated active sacroiliitis on MRI. Unenhanced CDUS showed a sensitivity of 17%, a specificity of 96%, a PPV of 65%, and an NPV of 72%; contrast-enhanced CDUS showed a sensitivity of 94%, a specificity of 86%, a PPV of 78%, and an NPV of 97%. Detection of vascularity in the SI joint was increased by contrast administration (P < 0.0001). Clustered receiver operating curve analysis demonstrated that enhanced CDUS (A(z) = 0.89) was significantly better than unenhanced CDUS (A(z) = 0.61) for the diagnosis of active sacroiliitis verified by MRI (P < 0.0001; 2-sided test). CONCLUSION: Microbubble contrast-enhanced CDUS is a sensitive technique with a high NPV for detection of active sacroiliitis compared with MRI.

Adult↗

PubMed2004

Low contrast dose voiding urosonography in children with phase inversion imaging.

Voiding urosonography (VUS) using a microbubble contrast agent has been introduced as an alternative technique in the diagnosis of vesicoureteral reflux (VUR). This study was undertaken to assess if phase inversion ultrasound (PIUS), a recent microbubble specific imaging technique, has advantages over fundamental in VUS and if it allows a reduction of contrast agent dose. Forty-three children with suspected VUR (aged 3 days-12 years, average of 3.9 years) with 92 kidney-ureter units (KUU) were included. Everyone obtained a baseline US scan that was followed by VUS using Levovist as the contrast agent. Constant switching between fundamental and PIUS performed the enhanced part for comparison. Every child underwent VCUG immediately afterwards. Contrast enhancement was stronger and longer lasting on PIUS than on fundamental US in all 43 cases. Reflux was detected in a total of 21 KUU, out of 92 KUU (23%). PIUS revealed VUR in 18; fundamental in 14 KUU and VCUG depicted 16 cases of reflux (p> or =0.29). The mean volume of Levovist dose administered to the bladder was 7.4+/-3.4% of the bladder volume. VUS using PI mode provided considerably stronger and longer enhancement and slightly improved the detection of VUR. It allowed a reduction of contrast dose and cost by approximately 35% over current dose recommendations for fundamental US.

Child↗

PubMed2004

Functional studies.

For the first time, functional studies with ultrasound have been made possible by the introduction of microbubble contrast agents. That they are confined to the circulation and that the small volume boluses that are effective are particular advantages when compared to iodinated and gadolinium-based agents. Classical indicator dilution calculations can be applied to the transit curves that can be measured as the contrast washes into and out of a region of interest. In addition, it is sometimes possible to measure the transit of the bolus through the supply artery and the draining vein, e.g. of a kidney and thus calculate the true transit time. Similar timing measurements have proved particularly useful for measuring the portosystemic shunts that are a feature of liver metastases and cirrhosis. A unique feature of microbubble contrast agents is their fragility when insonated at higher (but still permissible) powers. This can be used to create a negative bolus and the reperfusion of a slice of tissue can then be followed. From the exponential refill curve, features that relate to true tissue perfusion can be extracted.

Contrast Media↗

PubMed2005

Ultrasound: mechanical gene transfer into plant cells by sonoporation.

Development of nonviral gene transfer methods would be a valuable alternative of gene therapy or transformation. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation. Cavitation bubbles can induce cell death or transient membrane permeabilization (sonoporation) on cells. Application of sonoporation for gene transfer into cells or tissues develops quickly in recent years. Many studies have been performed in vitro exposure systems to a variety of cell lines transfected successfully. In vivo, cavitation initiation and control are more difficult, but can be enhanced by ultrasound contrast agents (microbubbles). The use of ultrasound for nonviral gene delivery has been applied for mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine. In this paper, ultrasound applied to plant cell transformation or gene transfer is reviewed. Recently, most researches are focused on sonication-assisted Agrobacterium-mediated transformation (SAAT) in plant cells or tissues. Microbubbles are also proposed to apply to gene transfer in plant cells and tissues.

Gene Transfer Techniques↗

PubMed2004

Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound.

We report the use of contrast-enhanced ultrasonography as an immediate means of assessing the clinical response to high-intensity focused ultrasound (US) or HIFU treatment of liver tumours. HIFU is a noninvasive transcutaneous technique for the ablation of tumours that has been shown to destroy tumour vasculature, as well as to cause coagulative necrosis of tumour cells. As a dynamic indicator of tissue perfusion, microbubble contrast agents have already been reported to increase the diagnostic sensitivity of ultrasonography in the detection of liver tumours. This report documents the ability of one i.v. microbubble contrast agent (SonoVue, Bracco, Italy) to delineate the extent of HIFU ablation by comparison of pre- and immediately posttreatment perfusion within the target tumour. Observed changes were seen to correlate well with the ablated volume on histologic evaluation of the treated volume. This is the first time that this imaging technique has been reported in this setting.

Adenocarcinoma↗

PubMed2006

Spatial control of gas bubbles and their effects on acoustic fields.

Because microbubbles can enhance therapy, such as by cavitation or by thermal means, treatment could be confined with localization of microbubbles. This spatial control can be achieved by the vaporization of liquid-filled droplets present throughout the medium in a process known as acoustic droplet vaporization (ADV). Bubbles in the form of an orthogonal plane or "wall" can thus be created and can scatter ultrasound to enhance the proximal acoustic field while shielding distal tissues. To investigate the possible effects of a preexistent bubble wall, tissue-mimicking polyacrylamide gels embedded with perfluorocarbon droplets were insonified under various conditions. The preliminary results presented in this paper show that a bubble wall can successfully cause proximal ADV at approximately half the transmitted pressures that are required without the use of a bubble wall, while also serving as a viable shield against ADV and potential damage in distal areas. The results seen here in a gel medium are promising and suggest further development in vivo is needed.

Acrylic Resins↗

PubMed2006

The relationship of acoustic emission and pulse-repetition frequency in the detection of gas body stability and cell death.

The effect of pulse-repetition frequency (PRF) and number of exposures on membrane damage and subsequent death of contrast agent-attached phagocytic cells was examined. Phagocytic cells of a mouse macrophage cell line were grown as monolayers on thin Mylar sheets. Optison microbubbles were attached to these cells by incubation. Focused ultrasound exposures (Pr = 2 MPa) were implemented at a frequency of 2.25 MHz with 46 cycle pulses and clinically relevant PRFs of 1 kHz, 100 Hz, 10 Hz, 1 Hz and 0.1 Hz in a degassed water bath. A 1-MHz receive transducer measured the scattered signal. The frequency spectrum was normalized to a control spectrum from linear scatterers. Photomicrographs of the cell monolayer were made before and after exposure, and a dye exclusion test (Trypan blue) was used to find the percentage of blue-stained cells indicating cell death, which was then related to acoustic emission. For 10 acoustic pulses and a high prerinse gas body concentration, there was less cell death and correspondingly lower change in the acoustic emissions at a PRF of 1 kHz than with PRFs of 100 Hz, 10 Hz, 1 Hz and 0.1 Hz (p < 0.001). The reduced effect at high PRF may be indicative of some evolution of the shelled microbubble that requires significant total exposure duration (> 10 ms, but < 100 ms).

Albumins↗

PubMed2006

Physical parameters affecting ultrasound/microbubble-mediated gene delivery efficiency in vitro.

Ultrasound (US)/microbubble-mediated gene delivery is a technology with many potential advantages suited to clinical application. Previous studies have demonstrated transfection but many are unsatisfactory in respect to the exposure apparatus, lack of definition of the US field or the limitations on parameters that can be explored using clinical diagnostic US machines. We investigated individual exposure parameters using a system minimising experimental artefacts and allowing control of many parameters of the US field. Using a 1-MHz transducer we systematically varied US parameters, the duration of exposure and the microbubble and DNA concentrations to optimise gene delivery. Delivery was achieved, using lipid microbubbles (SonoVue) and clinically acceptable US exposures, to adherent cells at efficiencies of approximately 4%. The acoustic pressure amplitude (0.25 MPa peak-negative), pulse repetition frequency (1-kHz) and duration of exposure (10 s) were important in optimising gene delivery with minimal impact on cell viability. These findings support the hypothesis that varying the physical parameters of US-mediated gene delivery has an affect on both efficiency and cell viability. These data are the first in terms of their thorough exploration of the US parameter space and will be the basis for more-informed approaches to developing clinical applications of this technology.

Animals↗

PubMed2006

Intraoperative brain ultrasound: a new approach to study flow dynamics in intracranial aneurysms.

The aim was to evaluate the potential of contrast-enhanced ultrasound to visualize the hemodynamics in intracranial aneurysms during neurosurgical intervention and to quantify the ultrasound data using digital particle image velocimetry (DPIV) technique. Aneurysms were scanned through the intact dura mater, preclipping and again postclipping after closure of the dura. After intravenous injection of Optison, angio-like views of the vascular tree surrounding the aneurysm, including the aneurysm sac, were obtained. Single ultrasound contrast agent microbubbles could be visualized in the aneurysm sac and the flow dynamics could be assessed in vivo. Spatial and temporal distributions of the velocity in the aneurysm and in the parent vessels were measured with DPIV using the backscattered signals from the microbubbles. Subsequently, the fluid stresses, vorticity, circulation, etc., were calculated from the velocity fields. We demonstrate in this paper that intraoperative contrast-enhanced ultrasound can be used to quantify the flow dynamics within an aneurysm.

Albumins↗

PubMed2006

Quantitative relations of acoustic inertial cavitation with sonoporation and cell viability.

Ultrasound-induced acoustic cavitation assists gene delivery, possibly by increasing the permeability of the cell membranes. How the cavitation dose is related to the sonoporation rate and the cell viability is still unknown and so this in vitro study quantitatively investigated the effects of cavitation induced by 1-MHz pulsed ultrasound waves and the contrast agent Levovist (containing microbubbles when reconstituted by adding saline and shaken) on the delivery of short DNA-FITC molecules into HeLa cells. The concentrations of cells and DNA-FITC were 2 x 10(5) cells/mL and 40 microg/mL, respectively. The cavitation was quantified as the inertial cavitation dose (ICD), corresponding to the spectral broadband signal enhancement during microbubble destruction. The relations of ICD with sonoporation and cell viability were examined for various acoustic pressures (0.48-1.32 MPa), Levovist concentrations (1.12 x 10(5)-1.12 x 10(7) bubbles/mL) and pulse durations (1-10 cycles). The linear regressions of the sonoporation rate versus ICD and the cell viability versus ICD were y = 28.67x + 10.71 (R(2) = 0.95) and z = -62.83x + 91.18 (R(2) = 0.84), respectively, where x is ICD, y is the sonoporation rate and z is the cell viability. These results show that the sonoporation rate and the cell viability are highly correlated with the ICD, indicating that sonoporation results may be potentially predicted using ICD.

Cell Membrane Permeability↗

PubMed2006

Intravascular inertial cavitation activity detection and quantification in vivo with Optison.

Inertial cavitation (IC) is an important mechanism by which ultrasound (US)-induced bioeffects can be produced. It has been reported that US-induced in vitro mechanical bioeffects with the presence of ultrasound contrast agents (UCAs) are highly correlated with quantified IC "dose" (ICD: cumulated root-mean-squared broadband noise amplitude in the frequency domain). The ICD has also been used to quantify IC activity in ex vivo perfused rabbit ear vessels. The in vivo experiments reported here using a rabbit ear vessel model were designed to: (1) detect and quantify IC activity in vivo within the constrained environment of rabbit auricular veins with the presence of Optison and (2) measure the temporal evolution of microbubble IC activity and the ICD generated during insonation treatment, as a function of acoustic parameters. Preselected regions-of-interest (ROI) in the rabbit ear vein were exposed to pulsed focused US (1.17 MHz, 1 Hz PRF). Experimental acoustic variables included peak rarefaction pressure amplitude ([PRPA]: 1.1, 3.0, 6.5 or 9.0 MPa) and pulse length (20, 100, 500 or 1000 cycles). ICD was quantified based on passive cavitation detection (PCD) measurements. The results show that: (1) after Optison injection, the time to onset of measurable microbubble IC activity was relatively consistent, approximately 20 s; (2) after reaching its peak value, the IC activity decayed exponentially and the half-life decay coefficient (t(1/2)) increased with increasing PRPA and pulse length; and (3) the normalized ICD generated by pulsed US exposure increased significantly with increasing PRPA and pulse length.

Albumins↗