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International audience; The use of impulsive acoustic radiation force for transient strain imaging was investigated and compared with conventional elastography. A series of experiments were performed to evaluate the performances of the technique on gelatine phantoms containing inclusions and to determine a range of applications where radiation force elastography may be useful compared with static elastography. Slip boundaries and cylindrical inclusions of varying elastic modulus were placed in background materials. A focused ultrasound transducer was used to apply localised radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain radio- frequency echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions. The highly localised and transient strain that is produced at depth permits the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography, due to greater independence from boundary conditions. In particular, radiation force elastograms were more homogeneous in the background and within the inclusions and displayed a superior contrast-transfer-efficiency, particularly for regions that had negative modulus contrast or that were disconnected from the background or the anterior medium by a low friction boundary.

A method for tracking the 3-D motion of tissues in real-time is combined with a 2-D high-intensity focused ultrasound (US), or HIFU, multichannel system to correct for respiratory motion during HIFU therapy. Motion estimation is based on an accurate ultrasonic speckle-tracking method. A pulse-echo sequence is performed for a subset of the transducers of the phased array. For each of these subapertures, the displacement is estimated by computing the 1-D cross-correlation of the backscattered signals acquired at two different times. The 3-D motion vector is then computed by a triangulation algorithm. This technique is experimentally validated in phantoms moving as fast as 40 mm s−1, and combined with HIFU sequences. A real-time feedback correction of the HIFU beam is achieved by adjusting the delays of each channel. The sonications “locked on target” are interleaved with very short motion-estimation sequences. Finally, in vitro experiments of “locked on target” HIFU therapy are performed in fresh moving tissues. (E-mail: mathieu.pernot@loa.espci.fr )

International audience; This article quantitatively investigates ultrasound propagation in numerical anisotropic porous media with finite-difference simulations in 3D. The propagation media consist of clusters of ellipsoidal scatterers randomly distributed in water, mimicking the anisotropic structure of cancellous bone. Velocities and attenuation coefficients of the ensemble-averaged transmitted wave (also known as the coherent wave) are measured in various configurations. As in real cancellous bone, one or two longitudinal modes emerge, depending on the micro-structure. The results are confronted with two standard theoretical approaches: Biot's theory, usually invoked in porous media, and the Independent Scattering Approximation (ISA), a classical first-order approach of multiple scattering theory. On the one hand, when only one longitudinal wave is observed, it is found that at porosities higher than 90% the ISA successfully predicts the attenuation coefficient (unlike Biot's theory), as well as the existence of negative dispersion. On the other hand, the ISA is not well suited to study two-wave propagation, unlike Biot's model, at least as far as wave speeds are concerned. No free fitting parameters were used for the application of Biot's theory. Finally we investigate the phase-shift between waves in the fluid and the solid structure, and compare them to Biot's predictions of in-phase and out-of-phase motions.

International audience; Targeted molecular imaging with ultrasound contrast agent microbubbles is achieved by incorporating targeting ligands on the bubble coating and allows for specific imaging of tissues affected by diseases. Improved understanding of the interplay between the acoustic forces acting on the bubbles during insonation with ultrasound and other forces (e.g. shear due to blood flow, binding of targeting ligands to receptors on cell membranes) can help improve the efficacy of this technique. This work focuses on the effects of the secondary acoustic radiation force, which causes bubbles to attract each other and may affect the adhesion of targeted bubbles. First, we examine the translational dynamics of ultrasound contrast agent microbubbles in contact with (but not adherent to) a semi-rigid membrane due to the secondary acoustic radiation force. An equation of motion that effectively accounts for the proximity of the membrane is developed, and the predictions of the model are compared with experimental data extracted from optical recordings at 15 million frames per second. A time-averaged model is also proposed and validated. In the second part of the paper, initial results on the translation due to the secondary acoustic radiation force of targeted, adherent bubbles are presented. Adherent bubbles are also found to move due to secondary acoustic radiation force, and a restoring force is observed that brings them back to their initial positions. For increasing magnitude of the secondary acoustic radiation force, a threshold is reached above which the adhesion of targeted microbubbles is disrupted. This points to the fact that secondary acoustic radiation forces can cause adherent bubbles to detach and alter the spatial distribution of targeted contrast agents bound to tissues during activation with ultrasound. While the details of the rupture of intermolecular bonds remain elusive, this work motivates the use of the secondary acoustic radiation force to measure the strength of adhesion of targeted microbubbles.

The influence of the stabilizing phospholipid-coating on the nonlinear dynamics of ultrasound contrast agent microbubbles is investigated. We record the radial dynamics of individual microbubbles with an ultra high-speed camera as a function of both driving pressure and frequency. The viscoelastic shell was found to enhance the nonlinear bubble response at acoustic pressures as low as 10 kPa. For increasing acoustic pressures a decrease of the frequency of maximum response was observed for a distinct class of bubbles, leading to a pronounced skewness of the resonance curve, which we show to be the origin of the "thresholding" behavior (Emmer et al. 2007). For the other bubbles, the frequency of maximum response was found to lie just above the resonance frequency of an uncoated microbubble and to be independent of the applied acoustic pressure. The shell-buckling bubble model (Marmottant et al. 2005), which accounts for buckling and rupture of the shell, captures both cases for a unique set of the shell parameters, the relevant parameter being the phospholipid concentration at the bubble interface. (E-mail: m.versluis@utwente.nl) (C) 2010 World Federation for Ultrasound in Medicine & Biology.

Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the change in the elasticity of the bubble shellwl as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles. (C) 2010 Acoustical Society of America. [DOI:10.1121/1.3493443]

International audience; Purpose: Delivering a drug close to the targeted cells improves its benefit versus risk ratio. A possible method for local drug delivery is to encapsulate the drug into solid microscopic carriers and to release it by ultrasound. The objective of this work was to use shock waves for delivering a molecule loaded in polymeric microcapsules. Material and methods: Ethyl benzoate (EBZ) was encapsulated in spherical gelatin shells by complex coacervation. A piezocomposite shock wave generator (120 mm in diameter, focused at 97 mm, pulse length 1.4 ls) was used for sonicating the capsules and delivering the molecule. Shock parameters (acoustic pressure, number of shocks and shock repetition frequency) were varied in order to measure their influence on EBZ release. A cavitation-inhibitor liquid (Ablasonic Ò) was then used to evaluate the role of cavitation in the capsule disruption. Results: The measurements showed that the mean quantity of released EBZ was proportional to the acoustic pressure of the shock wave (r 2 > 0.99), and increased with the number of applied shocks. Up to 88% of encapsulated EBZ could be released within 4 min only (240 shocks, 1 Hz). However, the quantity of released EBZ dropped at high shock rates (above 2 Hz). Ultrasound imaging sequences showed that cavitation clouds might form, at high shock rates, along the acoustic axis making the exposure inefficient. Measurements done in Ablasonic Ò showed that cavitation plays a major role in microcapsules disruption. Conclusions: In this study, we designed polymeric capsules that can be disrupted by shock waves. This type of microcapsule is theoretically a suitable vehicle for carrying hydrophobic drugs. Following these positive results, encapsulation of drugs is considered for further medical applications.