Properties Of Ultrasound Contrast Agents Research Articles

Nonlinear acoustic properties of ultrasound contrast agents encapsulated by an anisotropic visco-elastic shell

Nonlinear acoustic properties of ultrasound contrast agents encapsulated by an anisotropic visco-elastic shell

PD27-05 BENCHTOP BLADDER PHANTOM PRESSURE ESTIMATION USING ULTRASOUND CONTRAST AGENTS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-05 BENCHTOP BLADDER PHANTOM PRESSURE ESTIMATION USING ULTRASOUND CONTRAST AGENTS Kourosh Kalayeh, J. Brian Fowlkes, Jake Claflin, Mario L. Fabiilli, William W. Schultz, and Bryan S. Sack Kourosh KalayehKourosh Kalayeh More articles by this author , J. Brian FowlkesJ. Brian Fowlkes More articles by this author , Jake ClaflinJake Claflin More articles by this author , Mario L. FabiilliMario L. Fabiilli More articles by this author , William W. SchultzWilliam W. Schultz More articles by this author , and Bryan S. SackBryan S. Sack More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lack of a catheter-free, physiological method for evaluating bladder pressure is considered to be a major challenge in urodynamic testing. We hypothesize that pressure sensitive acoustic properties of ultrasound contrast agents (UCAs)–a method known as SubHarmonic Aided Pressure Estimation (SHAPE)–adequately estimates benchtop bladder phantom pressures. METHODS: The designed bladder phantom simulates non-voiding contractions (NVCs) and variable compliance. Laboratory made equivalent of a commercial UCA is diluted in 0.9 % normal saline (0.08 % v/v) and infused using urodynamic equipment (30 ml/min). Simultaneous subharmonic signal scattered by UCAs is acquired with ultrasound scanner (GE LOGIQ E10 and C2-9 probe using SHAPE mode) and calibrated with a linear fit to yield bladder pressure values. For the variable compliance bladder model, measurements are obtained at 10 cmH2O pressure increments while for the NVC model measurements are acquired continuously. RESULTS: Examples of pressure tracings and SHAPE estimations for the two models are shown. The maximum absolute errors for variable compliance and NVCs are less than 8 cmH2O (8 %) and 16 cmH2O (16 %), respectively. The mean R−squared values for both models (n=4) is R2=0.89±0.09. CONCLUSIONS: Subharmonic signal scattered by UCAs can be strongly correlated with phantom bladder pressures. This is the first step towards creating a catheter-free voiding bladder pressure measurement using SHAPE. Source of Funding: Societies for Pediatric Urology and UofM Mcubed © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e444-e445 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kourosh Kalayeh More articles by this author J. Brian Fowlkes More articles by this author Jake Claflin More articles by this author Mario L. Fabiilli More articles by this author William W. Schultz More articles by this author Bryan S. Sack More articles by this author Expand All Advertisement Loading ...

Contrast agent shell properties effects on heat deposition in bubble enhanced high intensity focused ultrasound.

The effects of the viscoelastic shell properties of ultrasound contrast agents on heat deposition in bubble enhanced high intensity focused ultrasound (HIFU) are studied numerically using a model that solves the ultrasound acoustic field and the multi-bubble dynamics. The propagation of the nonlinear acoustic waves in the test medium is modeled using the compressible Navier-Stokes equations in a fixed Eulerian grid, while the microbubbles are modeled as discrete flow singularities, which are tracked in a Lagrangian fashion. These two models are intimately coupled such that both the acoustic field and the bubbles influence each other at each time step. The resulting temperature rise in the field is then calculated by solving a heat transfer equation applied over a much longer time scale than the computed high frequency dynamics. Three shell models for the contrast agent are considered, and the effect of each of these models on the heat deposition at the focus is studied. The differences obtained in the bubble dynamics results between the shell models are discussed. The importance of modeling the elasticity of the shell is addressed by comparing the results between Newtonian and non-Newtonian shell models. Next, a parametric study varying the shell properties is carried out, and the relative roles of the shell viscosity and elasticity in affecting the heat deposition are discussed. These observations are then used to give recommendations for the design of innovative contrast agents, specifically for the purpose of obtaining higher heat deposition in bubble enhanced HIFU.

Window-Modulated Compounding Nakagami Parameter Ratio Approach for Assessing Muscle Perfusion with Contrast-Enhanced Ultrasound Imaging

The assessment of microvascular perfusion is essential for the diagnosis of a specific muscle disease. In comparison with the current available medical modalities, the contrast-enhanced ultrasound imaging is the simplest and fastest means for probing the tissue perfusion. Specifically, the perfusion parameters estimated from the ultrasound time-intensity curve (TIC) and statistics-based time–Nakagami parameter curve (TNC) approaches were found able to quantify the perfusion. However, due to insufficient tolerance on tissue clutters and subresolvable effects, these approaches remain short of reproducibility and robustness. Consequently, the window-modulated compounding (WMC) Nakagami parameter ratio imaging was proposed to alleviate these effects, by taking the ratio of WMC Nakagami parameters corresponding to the incidence of two different acoustic pressures from an employed transducer. The time–Nakagami parameter ratio curve (TNRC) approach was also developed to estimate perfusion parameters. Measurements for the assessment of muscle perfusion were performed from the flow phantom and animal subjects administrated with a bolus of ultrasound contrast agents. The TNRC approach demonstrated better sensitivity and tolerance of tissue clutters than those of TIC and TNC. The fusion image with the WMC Nakagami parameter ratio and B-mode images indicated that both the tissue structures and perfusion properties of ultrasound contrast agents may be better discerned.

Impact of temperature on the size distribution and shell properties of ultrasound contrast agents

Physical characterization of ultrasound contrast agents (UCAs) is important for their efficacious use in theragnostic applications. The goal of this study was to elucidate the impact of temperature on the size distribution and shell properties of Definity®, an FDA-approved clinical UCA. A Coulter counter (Multisizer IV) was modified to enable size measurements of UCAs at elevated temperatures. The size distribution and attenuation spectrum of Definity® was measured at room temperature (25 °C) and physiological temperature (37 °C), and used to estimate the shell stiffness and viscosity of the agent at both temperatures. The attenuation coefficient of Definity® increased by as much as 5 dB at 37 °C relative to 25 °C. The highest increase in attenuation was observed at 10 MHz, the resonance frequency of Definity®. However, no significant difference was observed in the size distribution of Definity® at 25 °C and 37 °C. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10-6 ± 0.07 × 10-6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10-6 ± 0.04 × 10-6 kg/s at 37 °C. These results indicate that the change in shell properties mediates the change in acoustic behavior of Definity® at physiological temperature.

Acoustic and optical characterization of targeted ultrasound contrast agents

We previously developed a flow cytometer system that incorporates the action of ultrasound to characterize shell properties of ultrasound contrast agents (UCA’s). The most recent manifestation involves a flow cytometer modified with a custom square quartz flow cell in place of the standard nozzle and fluid jet. Acoustic coupling to the carrier sheath fluid and UCA samples occurs through a PZT bonded to one side of the flow cell. The PZT-driven UCA oscillations were processed and fitted to the Marmottant UCA model. Shell properties for UCAs (including Definity, Optison, SonoVue, and even homemade bubbles) were determined. A major limitation of the previous work involved a lack of knowledge of the actual acoustic pressure incident on the UCA. The focus of this talk will be on optimization of the pressure inside the flow cell using finite element methods, and the comparison with additional measurements of unpublished data from targeted UCA’s. [Work funded in part by the Life Sciences Discovery Fund #3292512.]

Stress-induced Myocardial Ischaemia – Perfusion Contrast Echocardiography to Evaluate Presence and Severity of Coronary Artery Disease

The development of stable transpulmonary ultrasound contrast agents (UCAs) has allowed the echocardiographic assessment of myocardial perfusion, a technique known as myocardial contrast echocardiography (MCE). MCE exploits the ultrasonic properties of UCAs, which consist of acoustically active gas-filled microspheres. These are intravascular agents that have a rheology similar to red blood cells and thus allow analysis of myocardial blood flow both at rest and after stress. The combined assessment of wall motion and myocardial perfusion provides significant diagnostic and prognostic information during stress echocardiography. Functional imaging tests, such as myocardial perfusion scintigraphy and stress cardiac magnetic resonance imaging, are also used for non-invasive assessment of coronary disease. The principal advantages of MCE are that it does not expose the patient to ionising radiation or radioactive pharmaceuticals, is not contraindicated in patients with an implanted metallic device or who suffer from claustrophobia and it can be performed at the bedside. The purpose of this article is to outline the physiological principles underpinning ischaemia testing with MCE before proceeding to review the evidence base for MCE in patients with known or suspected coronary artery disease.

Advanced methods for perfusion analysis in echocardiography

It has been shown that besides positron emission tomography, single photon emission computed tomography and magnetic resonance imaging; contrast echocardiography can be used for qualitative and quantitative myocardial perfusion assessment. In this review, the properties of ultrasound contrast agents, imaging techniques and acquisition methods are shortly described and the possibilities of perfusion echocardiography are summarized. The main focus is put on the description of three perfusion models: mathematical models, physical models assuming an ideal inflow and physical models including inflow measurement.

Interaction of a high-order Bessel beam with a submerged spherical ultrasound contrast agent shell – Scattering theory

Background and objective Acoustic scattering properties of ultrasound contrast agents are useful in extending existing or developing new techniques for biomedical imaging applications. A useful first step in this direction is to investigate the acoustic scattering of a new class of acoustic beams, known as helicoidal high-order Bessel beams, to improve the understanding of their scattering characteristics by an ultrasound contrast agent, which at present is very limited. Method The transverse acoustic scattering of a commercially available albuminoidal ultrasound contrast agent shell filled with air or a denser gas such as perfluoropropane and placed in a helicoidal Bessel beam of any order is examined numerically. The shell is assumed to possess an outer radius a = 3.5 microns and a thickness of ∼105 nm. Moduli of the total and resonance transverse acoustic scattering form functions are numerically evaluated in the bandwidth 0 < ka ⩽ 3, which corresponds to a frequency bandwidth of 0–205 MHz that covers a wide range of applications for imaging with contrast agents. Particular attention is paid to the shell’s material, the content of its interior hollow region and the fluid surrounding its exterior. The contrast agent shell is assumed to be immersed in an ideal compressible fluid so the viscous corrections are not considered. Analytical equations are derived and numerical calculations of the total and resonance form functions are performed with particular emphasis on the effect of varying the half-cone angle, the order of the helicoidal Bessel beam as well as the fluid that fills the interior hollow space. Results and conclusion It is shown that shell wave resonance modes can be excited on an encapsulated micro-bubble. The forward and backscattering vanish for a helicoidal high-order Bessel beam. Additionally, the fluid filling the inner core affects the shell’s response significantly. Moreover, there is no monopole contribution to the axial scattering of a helicoidal Bessel beam of order m ⩾ 1 so that the dynamics of contrast agents would be significantly altered. The main finding of the present theory is the suppression or enhancement for a particular resonance that may be used to advantage in imaging with ultrasound contrast agents for clinical applications.

頸動脈プラーク病変における新生血管について―新画像法から―

Carotid artery stenosis should be discussed in relation to its frequency or after NASCET, ECST and ACAS surveys. We normally examine a patient's stenotic frequency through the narrow directions of angiography. It is possible that such evaluation is insufficient. The importance of the futures of a carotid artery wall, which is largely studied through ultrasound sonography, is well understood. The presence of ulceration, the surface condition and sonographic intensity of the plaque are routinely examined, but we focused on the existence of neovascularization in plaques, one of the pathological factors leading to plaque hemorrhage and rupture. This pathological process appears to be responsible for carotid artery stenosis, occlusion and artery-to-artery embolisms. Harmonic image is a contrast specific imaging modality that males use of the nonlinear properties of ultrasound contrast agents by transmitting at the fundamental frequency and receiving at multiples of these frequencies. Pulse inversion harmonic image (PIHI), using pulse inversion to eliminate and strengthen the harmonic frequency, is more effective than conventional harmonic imaging. We can detect a tissue perfusion by contrast sonographic imaging with PIHI. This method has already been reported on the clinical fields, e.g. in imaging cardiac infarction, liver tumors, brain tumors and cerebrovascular diseases. There are 2 routes of vascular wall feeding: diffusion through the endothelium, and diffusion through the vasa vasorum from the adventitious to the outer part of the medium. There is no neovascularization at the inner side of the carotid artery, but some plaques are associated with neovascularization in themselves, so an attempt was made to detect such plaques by the intermittent and real time contrast sonographic imaging method with PIHI. The evaluation of neovascularization by the intermittent method and its classification as Type I to IV, according to the distribution of neovascular vessels in the plaque, have already been reported. The real time contrast sonographic imaging method with PIHI has revealed some characteristics of neovascularization: 1. The newly formed vessels from the advantitia are larger than the ones from the endothelium. 2. There is some anastomosis between the neovasculatures. 3. The distribution of neovascular vessels is concentrated in an inner part of plaque. In addition, these vessels run in a spiral pattern. 4. Neovascular circulation is related to the pulsation of the carotid artery. 5. It seems that many newly formed vessels sprout from the endothelium.

On the impact of vessel size on the threshold of bubble collapse

Most of the studies investigating the physical properties of ultrasound contrast agents have addressed situations in which the microbubbles are contained in vessels much larger than the bubble size. Since contrast agents are normally injected into blood vessels, the investigation of their behavior in a confined environment may reveal useful information for the optimization of diagnostic and therapeutic applications of ultrasound. A series of experiments involving an ultrasound contrast agent in different sized silica and polyester tubes ranging from 50 to 400 microns in internal radius is presented. It is shown that the threshold for bubble collapse, as recorded by broadband acoustic emission, is not only dependent on the applied pressure amplitude but also on the tube size with an increase for smaller vessels. These data are interpreted and rationalized on the basis of a simple physical model. These findings may have implications for the evaluation of the risk of inertial cavitation in blood vessels. [Work supported by NIH RO1-EB003268 and by the Brigham Radiology Research and Education grant.]

Physical properties of ultrasound contrast agents

It has recently been shown that the new generation of contrast agents has suitable pressure ranges and driving pulse sequences for optimal imaging. Differences in imaging conditions are due to differences in physical properties of microbubbles of the ultrasound contrast agents: mechanical properties of shell materials and diffusion of encapsulated gases. In this study, bubble behaviors of two types of contrast agents were observed using a high-speed camera, and differences in mechanical properties of the shells and diffusion of the encapsulated gases were investigated. A microbubble was exposed to five ultrasound pulses with constant or increasing pressures with a pulse interval of 20 μs, and the bubbles exposed to each pulse were photographed using a high-speed camera. Definity® and Levovist® were used in the experiments. In the case of Definity®, amplitude of bubble oscillation increased with an increase in pulse pressure. In the case of Levovist®, discontinuous expansion of the bubble was observed during exposure to five pulses with increasing pressure, and it is thought that the strong non-linear relationship between oscillation amplitude and ultrasound pressure in the case of Levovist® is caused by the presence of bubble shells, which cannot be treated with a simple elastic model. Furthermore, shrinkage of bubble fragments was observed in the case of Levovist®, and it is thought that diffusion of encapsulated gas is accelerated by exposure to pulsed ultrasound.

ガラクトース製剤の懸濁液（Ｌｅｖｏｖｉｓｔ，Ｓｃｈｅｒｉｎｇ ＡＧ）を用いた経頭蓋超音波検査によるＰｅｒｆｕｓｉｏｎ Ｉｍａｇｅについて

Recently, the technique of harmonic contrast imaging has been developed which exploits the nonlinear properties of ultrasound contrast agents by processing the second harmonic echo signal of the transmitted ultrasound pulse. The contrast agent employed is Levovist (Schering), which was released in Japan in 1999. The advantage of harmonic imaging is its selective imaging of differences between tissue and blood perfusion areas.The purpose of the present study was to investigate a method of detecting human brain perfusion by ultrasound with second harmonic signals and contrast agents in eight patients with brain tumors. We used pulse inversion harmonic imaging, which is the latest technique for visualizing ultrasound contrast agents, thereby allowing us to image brain perfusion, and well enhanced perfusion images were obtained in all cases.We performed analysis resulting in wash-in wash-out curves, and concluded that this method could be used for diagnosis of brain hemodynamics.

Techniques for perfusion imaging with microbubble contrast agents.

The acoustic properties of ultrasound contrast agents vary widely with agent composition and insonation conditions. For contrast imaging, methods are required to match RF and Doppler processing to each combination of transmission parameters and agent and tissue properties. We propose a method that uses the measured or modeled echoes from agent and tissue to specify directly the characteristics of RF and Doppler filters for contrast imaging. The proposed method is sufficiently general to cover most common imaging techniques including harmonic greyscale, Doppler, and pulse inversion imaging. Using this method, sample filters were designed to detect myocardial perfusion with the contrast agent Optison (Mallinckrodt Medical, St. Louis, MO) under selected imaging conditions. Simplified power Doppler filtering, using a weighted sum of the Doppler samples, matched the performance of more complicated matrix filters. By coordinating the selection of RF and Doppler filters rather than designing these filters sequentially, agent-to-tissue contrast was increased by up to 3.9 dB. Under some conditions, fundamental RF filtering outperformed harmonic filtering for intermittent Doppler imaging.

Ultrasound Contrast Agents

The introduction of ultrasound contrast agents will bring new applications of this diagnostic imaging technology into clinical practice. Vascular, organ-specific, and oral agents are now in clinical trials and will soon be available. The development and properties of ultrasound contrast agents, most of which are based on gas-filled microbubbles, are reviewed. The first group of agents designed to overcome the limitations of free gas bubbles were of more uniform size but were either too large to cross the pulmonary capillary bed or lasted for only a short time in the circulation. The next group was able to produce enhancement over a period of minutes, but did not enhance the parenchyma of organs. The most recently developed intravenous agents exhibit parenchymal enhancement or are tissue-specific during B-mode imaging. Oral contrast agents may be used to reduce the artifacts created by gas in the gastrointestinal tract and to more clearly image the upper abdomen. Specific agents within each of the groups are described. The use of harmonic imaging is reviewed.

In vitro evaluation of acoustic properties of ultrasound contrast agents: experimental set-up and signal processing

The uses of ultrasound contrast agents are still growing since the first applications were reported by Gramiak and Shah. The contrast agent has to be more standardized with superior properties and the bubbles constituting the contrast agent must be small enough to cross microcirculation and to be sufficiently stable to cross from the injection site to the detection site. The aim of this study is the quantification of ultrasound contrast agents by determining their acoustic properties. The scatter properties are defined in terms of the backscatter transfer function and the transmission coefficient. The contrast agents are evaluated in their original states. The results obtained with Albunex (Molecular Biosystems) and Echovist 300 (Schering AG) are presented as well as a comparison between their acoustic characteristics.