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PubMedDate not supplied

In vitro analysis of ultrasound second generation contrast agent diluted in saline solution.

PURPOSE: To evaluate the changes in response of a second-generation sonographic contrast agent diluted in saline solution at different concentrations when different scanning techniques, and saline solution temperatures and pH were used. MATERIALS AND METHODS: A series of tests was devised to analyse the behaviour of the sonographic contrast agent at different concentrations, temperatures, pH and scanning techniques. Latex balloons were used as phantoms. These were filled with 0.9% Sodium Chloride solution mixed with a suspension of sulphur hexafluoride microbubbles stabilised with phospholipids (SonoVue ) and scanned with the harmonic imaging technique at low acoustic pressure. For each image obtained, we calculated the mean grey-scale level values and the standard deviations of grey-scale level were calculated within a ROI on the US images obtained; the resulting data were used to create echogenicity curves of UCA the echo-enhancer over time at the different conditions tested. RESULTS: We noted that SonoVue maintains adequate backscatter properties even at low concentration (0.15%) in N/S solution. The amount of echogenicity can be considered adequate for the average duration of an ultrasound examination. These properties are not affected by the scanning technique used on the phantom containing the UCA contrast agent/NaCl solution. The pH of the saline solution does not affect the survival of the microbubbles. Temperature becomes a significant value beyondover 33-37 degrees C; this condition favours rupture of the microbubbles with subsequent reduction of the echogenicity after 10-15 min, and complete disappearance after 30 min. US beam attenuation related to the concentration of the microbubbles in the saline solution volume has a non-linear behaviour; at low amplification levels, attenuation becomes more significant when using SonoVue concentrations higher than 0.4%. Unexpected greater improvement in US beam transmission was experienced for each of the three SonoVue concentrations tested, and especially for 0.2% and 0.4%, compared to saline solution alone. CONCLUSIONS: Our results show that a second-generation contrast agent may be used even diluted at low concentration in saline solution. This characteristic opens up new diagnostic perspectives possibilities for the use of contrast-enhanced harmonic imaging; in particular, its can be suggested used in hollow organs and functional studies. These in vitro results require by confirmation by clinical applications which are under evaluation and experimentation.

Contrast Media↗

PubMed1991

Hepatic lesions in the rabbit induced by acoustic cavitation.

Tissue damage during shock-wave lithotripsy is presumably secondary to cavitation phenomena involving the collapsus of gas bubbles in a fluid. To enhance shock-wave-related hepatic lesions, intravascular gas microbubbles were administered. Three groups of eight rabbits each received either 500 shock waves focused on the right hepatic lobe (group 1), gas microbubbles as a mixture of 50 cm3 of air with 50 cm3 of gelatin infused through an arterial catheter (group 2), or 500 shock waves and gas microbubbles simultaneously (group 3). In group 1, two animals had two to three subcapsular hepatic hematomas (diameter, less than 5 mm) and five had one to five intraparenchymal hematomas (less than 1 mm). In group 2, a moderate liver congestion was observed in three animals. In group 3, all animals had numerous subcapsular and intraperenchymal hematomas (2-30 mm). The hematomas were centered around the portal spaces, associated with lacunae (0.5-5 mm in diameter). Hematomas were also present on the anterior wall of intraabdominal organs. It was concluded that intravascular infusion of gas microbubbles into the path of a shock-wave generator dramatically enhances tissue damage. This technique, potentially useful in the treatment of hepatic tumors, needs refinement to confine lesions in a more uniform pattern to the targeted parenchyma.

Animals↗

PubMed1985

Improved intraoperative evaluation of mitral valve operations utilizing two-dimensional contrast echocardiography.

Whenever possible, precise mitral valve repair is preferable to valve replacement. Present methods for intraoperative detection of mitral regurgitation, primarily hemodynamic measurements and direct palpation, may underestimate or not detect the presence and severity of regurgitation. We have investigated two-dimensional contrast echocardiography as a means of improving our intraoperative assessment of mitral valve function both before and after repair or replacement. After exposure of the heart, a baseline two-dimensional echocardiogram (in modified long- and short-axis planes) is performed using a hand-held 5 mHz mechanical transducer. Five milliliters of agitated 5% dextrose in water is injected into the left ventricle through a transseptal needle to generate detectable microbubbles. In the absence of mitral regurgitation, virtually all microbubbles exit through the aorta; in the presence of regurgitation, a mass of microbubbles reflux into the left atrium. After repair of the mitral valve and immediately after bypass, the contrast echocardiogram is repeated and hemodynamic measurements are obtained. Forty-three patients (37 with mitral valve disease and six additional patients without mitral disease) undergoing cardiac operations were evaluated. Experience with intraoperative two-dimensional contrast echocardiography has accurately demonstrated relatively small degrees of mitral regurgitation when conventional techniques failed to do so and has allowed more precise repair of the residual regurgitation. Two commissurotomy and two annuloplasty patients who were thought to have satisfactory repairs underwent immediate second procedures because of significant residual mitral regurgitation demonstrated solely by this echocardiographic microbubble technique. No complications associated with this technique have developed. We conclude that intraoperative two-dimensional contrast echocardiography is a sensitive and safe technique that allows intraoperative detection of even small degrees of mitral regurgitation and provides a basis for precise repair of mitral valve lesions.

Adult↗

PubMed1993

Basic properties and results of clinical trials of ultrasound contrast agents based on galactose.

The development of reproducible echogenic contrast agents, which contain physiologically degradable acoustic strays in micrometre dimensions, has been under way for several years; all currently known industrial echocontrast agents are based on microbubbles, due to their special acoustic properties. The currently known echogenic contrast agents can be divided into three physically different types: microbubble-containing liquids, gas-filled microspheres and microbubble-containing suspensions (e.g. SH U 454-Echovist and SH U 508 A). The agents SH U 454 and SH U 508 A are based on galactose microparticles, which are suspended shortly before use. After intravenous injection, SH U 454 dissolves after leaving the right heart before the left heart is reached. SH U 508 A displays greater intravascular stability than SH U 454 and leads to an increase of the echogenicity in the blood which, after intravenous injection, survives pulmonary transit and reaches the arterial vascular bed. This indicates that the microbubbles are stable under physiological pressures. After intravascular dissolution of the microstructures, the remaining galactose (a monosaccharide with no known allergenic potential) is degraded physiologically. To date, a total of more than 2,500 patients has been examined in clinical trials with SH U 454 (Echovist). The intravenous administration of this contrast agent was well tolerated; in particular, no substance-induced severe adverse events were observed, and no clinically relevant changes of cardiovascular function or of laboratory parameters occurred. Extensive clinical experience has been gained in the main indications echocardiography (> 1,850 patients), venous vessels (> 200 patients) and hysterosalpingocontrast sonography (> 500 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1997

Overview of echo-enhanced vascular ultrasound imaging for clinical diagnosis in neurosonology.

Small gas bubbles have been used as ultrasound signal enhancers for many years. However, only recently have microbubble preparations become available that provide useful and reproducible enhancement on ultrasound scans after i.v. administration. Levovist is a galactose/palmitic acid-based agent that, on dissolution and agitation in sterile water, generates air-filled microbubbles with a palmitic acid coating and a median diameter of 2 microns. These lipid-coated microbubbles are sufficiently small and stable to survive the cardiopulmonary circulation and to enhance the entire blood pool. In Doppler, these microbubbles increase the signal by 10 dB to 30 dB, enabling detection of flow in situations for which attenuation would otherwise render impossible, e.g., transcranially approached intracranial vessels. Echo enhancement can increase the technical success rate of the examination, reduce examination time, and allow color imaging and pulsed Doppler detection of a greater number of vessels. The low volume of flow in the preocclusive carotid lesion, whose unsatisfactory detection often necessitates angiography, is a second area in which these agents may make an impact. Other applications, such as using the agent as an indicator for bolus dilution estimates of flow and transit time, remain to be exploited. However, certain problems remain. The bolus character of the enhancement presents a challenge to the clinical practice of ultrasound, in which Doppler interrogation over tens of minutes is commonplace; perhaps infusions may be necessary in the future. Detection of smaller volumes of blood in smaller vessels is determined not only by strength of the enhanced Doppler signal from blood but also on interference from the much larger echo from slowly moving tissue. This forces use of a clutter or "thump" filter, which also eliminates the detected slow flow. Echo-enhancing agents combined with harmonic imaging-a new method that exploits the nonlinear oscillation of the bubbles in the ultrasound field-offers an entirely new way to suppress the effects of clutter and hence to detect flow in very small vessels, even in moving tissue.

Albumins↗

PubMed1998

[Usefulness of CO2 US angiography in treating hepatocellular carcinoma].

We evaluated the usefulness of CO2 US angiography in the detectability of and the effectiveness of TAE and/or PEIT for hepatocellular carcinoma (HCC). Twenty-three patients with HCC underwent CO2 angiography during the interventional procedure to treat HCC after examination of CT and conventional US. CO2 US angiography was observed on the US monitor by injecting CO2 microbubbles through a catheter placed in the hepatic artery. Contrast materials for CO2 US angiography were 3 ml of CO2 microbubbles prepared by vigorously mixing 3 ml of normal saline with 3 ml of 20% Intralipid, 3 ml of 20% albumin or 3 ml of the patient's own blood. In all patients, CO2 US angiography revealed equal or superior tumor detectability as compared with CT, conventional US and angiography. For demonstrating the inner structure of HCC, the image of CO2 microbubbles mixed with Intralipid was better than that of CO2 microbubbles mixed with albumin. In 9 of 23 patients, CO2 US angiography depicted nodules that had not been seen in the other images. TAE was performed in 21 patients with HCC who showed hypervascularity. In one patient in whom it was difficult to clearly depict the small lesion of HCC by conventional angiography and US, PEIT was successful under CO2 US angiography. The detectability of HCC was higher in CO2 US angiography than in CT, conventional US or angiography. The distribution of blood supply to HCC was observed easily by CO2 US angiography. In TAE of HCC, CO2 US angiography was useful to determine the dose of embolization materials without having to perform repeated angiography. It was possible to perform PEIT easily for non-detectable tumors without CO2 US angiography. CO2 US angiography was useful to evaluate the stage of HCC and to perform TAE and PEIT.

Aged↗

PubMed2005

[Ultrasound contrast agents--physical basics].

The concept of ultrasound contrast agents (UCA) is based on the inherent physical and acoustical properties of gas-filled microbubbles within an ultrasonic (US) field. Depending on the magnitude of the incident US wave different scattering behavior occurs. While it is linear for low acoustic pressures, increasing it leads to the occurrence of nonlinear effects, such as emission of harmonics. High pressure results in destruction of the bubbles producing a highly nonlinear echo signal. Using these specific acoustic signatures opens new perspectives for the development of bubble-specific imaging techniques such as harmonic or intermittent imaging. This review deals with the physical properties of the gas-filled microbubbles, their behavior within an ultrasonic field, and the use of the bubbles' acoustic signatures for contrast-specific imaging. Novel applications such as tissue-specific microbubbles, targeted imaging, and therapeutic applications using the bubbles as vehicles for drug or gene delivery are discussed as well as acoustically induced bioeffects and considerations for the safe use of UCA from an acoustic standpoint.

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PubMed2004

Liver metastases in cancer: detection with contrast-enhanced ultrasonography.

In patients with known or suspected malignancy, ultrasonography (US) is often the first choice for liver imaging because of its widespread availability and low cost. Compared with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), the sensitivity of conventional US for detecting hepatic metastases is relatively poor. The advent of microbubble contrast agents changed this situation. Sensitivity and specificity increased substantially with the use of these contrast agents and contrast-specific imaging modes in recent years. Currently, numerous US imaging methods exist, based on Doppler techniques or harmonic imaging. They exploit the complex nonlinear behavior of microbubbles in a sound field to achieve marked augmentation of the US signal. Although microbubble contrast agents are essentially blood pool agents, some have a hepatosplenic specific late phase. Imaging during this late phase is particularly useful for improving the detection of malignant liver lesions and allows US to perform similarly to spiral CT as shown by recent studies. In addition, this late phase imaging is very helpful for lesion characterization. Low mechanical index imaging with the newer perfluor agents permits real-time imaging of the dynamic contrast behavior during the arterial, portal venous, and late phases and is particularly helpful for lesion characterization. The use of US for hemodynamic studies of the liver transit time may detect blood flow changes induced by micrometastases even before they become visible on imaging. In this field of functional imaging, further research is required to achieve conclusive results, which are not yet available.

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PubMed2004

Ultrasound contrast agents can influence the respiratory burst activity of human neutrophil granulocytes.

Activated leucocytes can bind and, subsequently, phagocytose microbubbles that are used as ultrasound (US) contrast agents. The purpose of this study was to investigate whether or not microbubbles can influence the inflammatory response of human neutrophil granulocytes. Granulocytes isolated from healthy volunteers were activated with various stimuli, for example, the bacterial peptide N-formyl-methyonyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, the protein kinase C activator phorbol myristate acetate (PMA) and the cytokine tumor necrosis factor alpha (TNF-alpha), and incubated with albumin or phospholipid microbubbles. Neutrophil respiratory burst activity and elastase release were quantified. Albumin (Optison) and phospholipid (SonoVue) contrast agents induced an extensive oxidative response of human granulocytes to all the stimuli used, and these effects could be significantly impaired by preincubation of the cells with cytochalasin B. Left heart contrast agents used for contrast-enhanced US assessment can activate human neutrophil granulocytes, inducing an extensive respiratory burst to secondary stimuli. The potential clinical relevance of this effect needs to be elucidated.

Albumins↗

PubMed2006

Ultrasound imaging and contrast agents: a safe alternative to MRI?

Microbubble contrast media are used to enhance ultrasound images. Because ultrasound is a real-time investigation, contrast-enhanced ultrasound offers possibilities for perfusion imaging. This review is conducted to evaluate the safety of contrast-enhanced ultrasound and its possible role in medical imaging. The safety of diagnostic ultrasound is still an important field of research. The wanted and unwanted effects of ultrasound and microbubble contrast media as well as the effects of ultrasound on these microbubbles are described. Furthermore, some of the possible applications and indications of contrast-enhanced ultrasound will be discussed. The shared advantages of MRI and ultrasound are the use of non-ionizing radiation and non-nephrotoxic contrast media. From this review it can be concluded that, for certain indications, contrast enhanced ultrasound could be a safe alternative to MRI and a valuable addition to medical imaging.

Contrast Media↗

PubMed2005

High-frequency dynamics of ultrasound contrast agents.

Ultrasound contrast agents enhance echoes from the microvasculature and enable the visualization of flow in smaller vessels. Here, we optically and acoustically investigate microbubble oscillation and echoes following insonation with a 10 MHz center frequency pulse. A high-speed camera system with a temporal resolution of 10 ns, which provides two-dimensional (2-D) frame images and streak images, is used in optical experiments. Two confocally aligned transducers, transmitting at 10 MHz and receiving at 5 MHz, are used in acoustical experiments in order to detect subharmonic components. Results of a numerical evaluation of the modified Rayleigh-Plesset equation are used to predict the dynamics of a microbubble and are compared to results of in vitro experiments. From the optical observations of a single microbubble, nonlinear oscillation, destruction, and radiation force are observed. The maximum bubble expansion, resulting from insonation with a 20-cycle, 10-MHz linear chirp with a peak negative pressure of 3.5 MPa, has been evaluated. For an initial diameter ranging from 1.5 to 5 microm, a maximum diameter less than 8 microm is produced during insonation. Optical and acoustical experiments provide insight into the mechanisms of destruction, including fragmentation and active diffusion. High-frequency pulse transmission may provide the opportunity to detect contrast echoes resulting from a single pulse, may be robust in the presence of tissue motion, and may provide the opportunity to incorporate high-frequency ultrasound into destruction-replenishment techniques.

Contrast Media↗

PubMed2004

Basic study on velocity-flow urodynamics using Doppler sonography: simultaneous detection of cavitation and Doppler signals in an artificial urethral model.

BACKGROUND: We have developed velocity-flow urodynamics using Doppler sonography based on the hypothesis that microbubbles formed in the urethra are responsible for Doppler signals. In order to confirm this hypothesis derived from Bernoulli's principle, we investigated the simultaneous detection of cavitation noise and Doppler signals in an experimental system. METHODS: An experimental circuit was built in which a stenosis was created using a glass or silicon tube with tap water used as the sample fluid. Doppler signals, pressure before and after the stenosis, flow rate, flow velocity and cavitation noise were measured. Direct detection of cavitation with a high-speed charged-coupled device (CCD) camera was conducted in the glass tube. The relationship between cross-sectional area and flow velocity in terms of the detection of Doppler signals was analyzed in the silicon tube study. RESULTS: In the glass tube study, a high-speed CCD camera clearly detected masses of microbubbles associated with cavitation. The range of flow rates creating cavitation completely corresponded with those producing Doppler signals detected by ultrasonography. A similar correlation was observed in the silicon tube study, which showed that a low flow velocity of 41.5 cm/sec through a stenosis with a cross-sectional area of 20 mm(2) created Doppler signals at a flow rate of 8.3 mL/sec. CONCLUSION: The results of the present study confirmed that microbubbles created in flowing urine are responsible for Doppler signals. Measurement of velocity-flow urodynamics has great potential to become a non-invasive and reliable alternative to conventional pressure- flow urodynamic studies.

Humans↗

PubMed2006

Angiogenesis: noninvasive quantitative assessment with contrast-enhanced functional US in murine model.

PURPOSE: To evaluate quantitative functional ultrasonography (US) in a murine gel model by using microbubble destruction kinetics to determine whether parametric indices provided with US could help assess angiogenesis. MATERIALS AND METHODS: Institutional Animal Subjects Committee approved experiments and procedures. In 36 normal mice, two 0.4-mL gel implants were placed subcutaneously on either side of spine. One implant contained 0.5, 1.0, or 1.5 microg human basic fibroblast growth factor (bFGF) per milliliter of gel. Functional US quantitative analysis of angiogenesis with microbubble contrast agent was performed on days 3, 6, 9, and 12; histologic data were collected. Time-intensity curve of implant was fitted to mathematic decay model to calculate fractional blood volume and fraction of blood replaced per unit of time. Microvascular density (MVD) and percentage of microvascular area (MVA) were measured after anti-CD31 staining. Spearman rank order correlation was used in analyses. RESULTS: bFGF-containing implants induced MVD of eight, 35, 42, and 42 vessels per square millimeter on days 3, 6, 9, and 12, respectively; in controls, MVD was four vessels/mm2 (P<.05 on days 6, 9, and 12). bFGF-containing implants induced percentage MVA of 2%, 5%, 20%, and 27%, respectively; in controls, it was 0.5% (P<.05). Maximum enhancement was significantly increased in bFGF implants (23.3 gray level+/-14.1 [standard deviation]) compared with controls (11.0+/-5.5, P<.001). Implants containing bFGF showed poor correlations between fractional blood volume and MVD (r2=0.42) or percentage MVA (r2=0.51) at US. There was no correlation between microbubble velocity and MVD (r2<0.05) or percentage MVA (r2<0.13). CONCLUSION: Functional US perfusion parameters do not correlate with current histologic indices for quantifying angiogenesis. MVD, as a histologic quantitative measurement of angiogenesis, may not be an appropriate standard for contrast-enhanced imaging that relies on perfused neovessels.

Animals↗

PubMed2007

Myocardial ischemic memory imaging with molecular echocardiography.

BACKGROUND: Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium. METHODS AND RESULTS: Lipid microbubbles (diameter, 3.3+/-1.7 microm) were synthesized. The selectin ligand sialyl Lewis(x) was conjugated to the microbubble surface (MB(sLex)). Control bubbles (MB(CTL)) bore surface Lewis(x) or sialyl Lewis(c). Intravital microscopy of mouse cremaster muscle was performed after intravenous injection of MB(sLex) (n=11) or MB(CTL) (n=9) with or without prior intrascrotal tumor necrosis factor-alpha. There was greater adhesion of MB(sLex) to inflamed versus noninflamed endothelium (P = 0.0081). Rats (n=12) underwent 15 minutes of anterior descending coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high-mechanical-index nonlinear echocardiographic imaging was performed in which single frames were acquired at 3.5 and 4 minutes after intravenous injection of MB(sLex) or MB(CTL). Video intensity at 4 minutes was subtracted from that at 3.5 minutes to derive target-specific acoustic signal. MB(sLex) caused greater opacification in postischemic versus nonischemic myocardium at both time points (P < or = 0.002). Immunostaining confirmed endothelial P-selectin expression in the ischemic bed. CONCLUSIONS: Echocardiographic identification of recently ischemic myocardium is possible using ultrasound contrast agents targeted to selectins. This may offer a new approach to the more timely and precise diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain cardiac origin.

Animals↗

PubMed2006

Waveform design for ultrasonic pulse-inversion fundamental imaging.

Pulse-inversion (PI) fundamental imaging exhibits significantly better contrast detection than linear and second-harmonic imaging. PI fundamental imaging involves two firings with inverted waveforms. When the returning echoes from the two firings are summed, the residual signal related to tissue is limited to even-order harmonics, whereas for microbubbles, the fundamental signal is not completely canceled due to the echo under compression differing from that under rarefaction. The efficacy of PI fundamental imaging has been reported previously. In this study, we investigated the performance of PI fundamental imaging using both simulations and in vitro experiments with various transmit waveforms, including coded excitation and asymmetrical waveforms (i.e., asymmetrical between compression and rarefaction). For coded excitation, a longer waveform was found to increase the similarity in the responses to positive and negative pulses, thus lowering the contrast between microbubbles and tissue. In addition, imperfect pulse compression also decreases the contrast because it increases the residue fundamental signal emanating from tissue. Using asymmetrical waveforms noticeably increased the residual microbubble signal in the fundamental band but the nonzero DC component that is inherent in such waveforms also increases the tissue fundamental signal. The combination of these two effects decreases the contrast. From these results, it is concluded that the use of coded excitation is undesirable in PI fundamental imaging and that the waveforms should contain no DC component. Furthermore, the transmit waveform needs to be appropriately windowed in order to reduce spectral leakage. Therefore, a Gaussian pulse with the pulse length determined by the signal-to-noise ratio of the imaging system is generally optimal for PI fundamental imaging.

Artifacts↗

PubMed2006

[Development of plasmid DNA-based gene transfer].

Gene therapy based on ultrasound with microbubbles offers a novel approach for the prevention and treatment of variety of diseases. The major development of gene transfer has importantly contributed to intense investigation of the potential of gene therapy in cancer or cardiovascular medicine. The amazing advances in molecular biology have provided a dramatic improvement of the technology that is necessary to transfer target genes into somatic cells. Gene transfer methods have been surprisingly improved. In fact, some of them (retroviral vectors, adenoviral vectors or liposome based vectors, etc.) have been used in the clinical trials already. But some severe side effects were reported in clinical gene therapy using such viral, so people desire safe and efficient clinical gene therapy. Recently, ultrasound-mediated gene transfer has been reported to augment the transfection efficiency and facilitate local gene expression. Interestingly, gene transfer into the fetal central nervous system was successfully achieved by intrauterine injection with microbubble-enhanced ultrasound. Compared to other viral vectors, there are some theoretical advantages including safety, simplicity of preparation, and local gene transfer. Thus, we focused on the development of gene transfer using naked plasmid DNA with an ultrasound or microbubble-enhanced ultrasound method.

Animals↗

PubMed2005

Tumor vessel compression hinders perfusion of ultrasonographic contrast agents.

Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 microm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.

Albumins↗

PubMed2004

Advantages in using multi-frequency driving ultrasound for optimizing echo particle image velocimetry techniques.

We have recently developed an ultrasound based velocimetry technique, termed echo particle image velocimetry (echo PIV). This method takes advantage of the non-linear backscatter characteristics of ultrasound contrast microbubbles when exposed to certain ultrasonic field. Preliminary in vitro, animal and clinical studies have shown significant promise of this method for measuring multiple velocity components with good temporal and spatial resolution. However, there is still difficulty in maximizing the non-linearity of bubble backscatter using conventional Gaussian-pulse excitation techniques because significant harmonic components may not be produced at modest pressure amplitudes and the higher incident pressure amplitudes required to induce non-linear behavior may cause bubble destruction. We present here a potential solution to this problem through the use of multi-frequency excitation. A rectangular pulse with multiple harmonics is used to drive the bubble. The backscatter process is studied through a modified Rayleigh-Plesset equation. Results show that the rectangular wave is effective in improving the visibility of microbubbles with ultrasound backscattered efficiency significantly higher than the widely used Gaussian waveform. Use of rectangular pulses with 4 and 2 harmonics showed no significant difference in bubble backscatter behavior, indicating that a two-frequency excitation may be sufficient to induce non-linear behavior of the microbubbles practically at modest incident pressures.

Algorithms↗