Broadband attenuation measurement has been widely used for characterizing ultrasound contrast agents. Chen et al. (2002) recently suggested that broadband attenuation data depend on the center frequency of the broadband excitation pulse and, therefore, that they are not a reliable measure of the bubble behavior. We investigated the suitability of measurement of broadband attenuation as a characterizing tool using the contrast agent Definity® as a test case. Analyzing the attenuation data obtained with three broadband unfocused transducers with different center frequencies (2.25, 3.5 and 5 MHz), we found that attenuation is independent of the transducer used and matches in the overlap regions of any two transducers. Attenuation does not depend on excitation pressure amplitude as long as the excitation amplitude remains below a critical value (≈ 0.26 MPa), indicating that the measurement of broadband attenuation below critical excitation can, indeed, be used for characterization. Furthermore, the linear relationship of attenuation with concentrations of Definity® is also investigated. © 2005 World Federation for Ultrasound in Medicine & Biology.

Dhiman Chatterjee

Department of Mechanical Engineering

Linear systems

transducers

Ultrasonics

BROADBAND ATTENUATION

Broadband excitation

PRESSURE AMPLITUDE

Attenuation

contrast medium

PERFLUTREN

article

Data analysis

Linear system

microbubble

priority journal

reliability

SIGNAL AVERAGED ELECTROCARDIOGRAPHY

ULTRASOUND TRANSDUCER

Contrast Media

Fluorocarbons

Humans

Microbubbles

Scattering, Radiation

Sensitivity and Specificity

Signal Processing, Computer-Assisted

ULTRASONOGRAPHY, INTERVENTIONAL

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Ultrasound in Medicine and Biology

Two nonlinear interfacial elasticity models-interfacial elasticity decreasing linearly and exponentially with area fraction-are developed for the encapsulation of contrast microbubbles. The strain softening (decreasing elasticity) results from the decreasing association between the constitutive molecules of the encapsulation. The models are used to find the characteristic properties (surface tension, interfacial elasticity, interfacial viscosity and nonlinear elasticity parameters) for a commercial contrast agent. Properties are found using the ultrasound attenuation measured through a suspension of contrast agent. Dynamics of the resulting models are simulated, compared with other existing models and discussed. Imposing non-negativity on the effective surface tension (the encapsulation experiences no net compressive stress) shows "compression-only" behavior. The exponential and the quadratic (linearly varying elasticity) models result in similar behaviors. The validity of the models is investigated by comparing their predictions of the scattered nonlinear response for the contrast agent at higher excitations against experimental measurement. All models predict well the scattered fundamental response. The nonlinear strain softening included in the proposed elastic models of the encapsulation improves their ability to predict subharmonic response. They predict the threshold excitation for the initiation of subharmonic response and its subsequent saturation. © 2010 Acoustical Society of America.

Fulltext

Journal of the Acoustical Society of America

Material characterization of the encapsulation of an ultrasound contrast microbubble and its subharmonic response: Strain-softening interfacial elasticity model

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of commercial contrast agents such as Optison (GE Health Care, Princeton, NJ) and Definity (Bristol Meyer-Squibb Imaging, North Ballerina, MA). We have developed an interfacial rheology model for the encapsulation of such microbubbles. By matching with experimental data, we obtain the characteristic rheological parameters. We compare model predictions with other experiments. We also investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. Three regions of acoustic pressure amplitudes are found: at low pressure, there is no destruction; at slightly higher pressure bubbles are destroyed, and the rate of destruction depends on a combination of PRF and amplitude. At a still higher pressure amplitude, the attenuation decreases catastrophically. The last two regimes correspond respectively to 1) slow destruction of bubbles due to increased gas diffusion and 2) complete bubble destruction leading to release of free bubbles. An analytical model for the bubble growth and dissolution will be presented. The effects of membrane permeability and elasticity on the stability of microbubbles are investigated. (Supported by DOD, NSF and NIH). © 2008 American Institute of Physics.

AIP Conference Proceedings

Modeling and characterization of encapsulated microbubbles for ultrasound imaging and drug delivery

Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of commercial contrast agents such as Sonazoid and Definity. We have developed a number of different interfacial rheology models for the encapsulation of such microbubbles. By matching with experimentally measured attenuation, we obtain the characteristic rheological parameters. We compare model predictions with measured subharmonic responses. We also investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data. © 2006 American Institute of Physics.

Characterization and ultrasound-pulse mediated destruction of ultrasound contrast microbubbles

Micron-size bubbles encapsulated by a stabilizing layer of surface-active materials are used in medical ultrasound imaging and drug delivery. Their destruction stimulated by ultrasound plays a critical role in both applications. We investigate the destruction process of microbubbles in a commercially available contrast agent by measuring the attenuation of ultrasound through it. The measurement is performed with single-cycle bursts from an unfocused transducer (with a center frequency of 5 MHz) for varying pressure amplitudes at 50-, 100-, and 200-Hz pulse repetition frequencies (PRF) with duty cycles 0.001%, 0.002%, and 0.004%, respectively. At low excitation, the attenuation is found to increase with time. With increased excitation level, the attenuation level decreases with time, indicating destruction of microbubbles. There is a critical pressure amplitude (∼1.2 MPa) for all three PRFs, below which there is no significant bubble destruction. Above the critical pressure amplitudes the rate of destruction depends on excitation levels. But at high-pressure amplitudes the destruction becomes independent of excitation pressure amplitude. The results are interpreted to identify two different mechanisms of bubble destruction by its signature in attenuation, namely, slow dissolution by diffusion and catastrophic shell rupture. The different modes are discussed in detail with their implications in medical applications. © 2005 American Institute of Physics.

Physics of Fluids

Ultrasound-mediated destruction of contrast microbubbles used for medical imaging and drug delivery

Zero-thickness interface models are developed to describe the encapsulation of microbubble contrast agents. Two different Rheological models of the interface, Newtonian (viscous) and viscoelastic, with rheological parameters such as surface tension, surface dilatational viscosity, and surface dilatational elasticity are presented to characterize the encapsulation. The models are applied to characterize a widely used microbubble based ultrasound contrast agent. Attenuation of ultrasound passing through a solution of contrast agent is measured. The model parameters for the contrast agent are determined by matching the linearized model dynamics with measured attenuation data. The models are investigated for its ability to match with other experiments. Specifically, model predictions are compared with scattered fundamental and subharmonic responses. Experiments and model prediction results are discussed along with those obtained using an existing model [Church, J. Acoust. Soc. Am. 97, 1510 (1995) and Hoff et al., J. Acoust. Soc. Am. 107, 2272 (2000)] of contrast agents. © 2005 Acoustical Society of America.

Characterization of ultrasound contrast microbubbles using in vitro experiments and viscous and viscoelastic interface models for encapsulation

Ultrasound in Medicine & Biology

A Newtonian rheological model for the interface of microbubble contrast agents

Pressure-dependent attenuation in ultrasound contrast agents

IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control

Experimental and theoretical evaluation of microbubble behavior: effect of transmitted phase and bubble size

Predicting the acoustic response of a microbubble population for contrast imaging in medical ultrasound

On the suitability of broadband attenuation measurement for characterizing contrast microbubbles

Journal	Ultrasound in Medicine and Biology
ISSN	03015629
Open Access	No