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Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces

Valeria Garbin1, Marlies Overvelde2, Benjamin Dollet3, Nico de Jong2,4, Detlef Lohse2 and Michel Versluis2

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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.


PACS

87.63.D- Ultrasonography

47.55.dd Bubble dynamics

43.80.Qf Medical diagnosis with acoustics (in PACS, see also 87.63.D−)

87.57.C- Image quality

43.80.Cs Acoustical characteristics of biological media: molecular species, cellular level tissues

87.19.X- Diseases

Subjects

Fluid dynamics

Biological physics

Medical physics

Dates

Issue 19 (7 October 2011)

Received 11 May 2011, in final form 29 July 2011

Published 30 August 2011



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