Target drug and gene delivery are rapidly emerging applications for ultrasound contrast agents since they reduce potential deleterious side effects to healthy tissue and minimize the overall dose needed. Development of new contrast agents requires a good understanding of the effect of the properties of the viscous material of the shell and of the acoustic field on the dynamics of the agent and on the mechanism of breakup of the shell. A novel numerical code, which enables modeling of non-spherical contrast agent's dynamics acoustic waves and nearby boundaries and tissues is proposed. This model, whose feasibility was demonstrated in Phase I, will allow us to accurately predict the necessary conditions for breakup. In Phase I we coupled a Boundary Element Method solver and a Navier-Stokes solver and demonstrated 3D modeling of viscous thick shelled contrast agent including in the presence of rigid walls, and identified the mechanisms for shell breakup due to non-spherical deformations. In the Phase II study, we will complete, improve and expand the capabilities of the model to simulate viscoelastic shell material properties and simulate multiple contrast agents'interactions with deformable boundaries such as blood cells, tissues, and blood vessels. We will also validate the developed model experimentally using both a scaled-up test for visualization and actual contrast agents for breakup limit confirmation.

Public Health Relevance

Success of this research will help pharmaceutical companies develop safer and more efficient drug and gene delivery agents. These agents are especially attractive to chemotherapy treatment because they can greatly reduce deleterious side effects to healthy tissue caused by many chemotherapy drugs and minimize the overall dose needed.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-SBIB-S (91))
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Lopez, Hector
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Dynaflow, Inc.
United States
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Hsiao, C-T; Choi, J-K; Singh, S et al. (2013) Modelling single- and tandem-bubble dynamics between two parallel plates for biomedical applications. J Fluid Mech 716:
Hsiao, Chao-Tsung; Chahine, Georges L (2013) Breakup of finite thickness viscous shell microbubbles by ultrasound: a simplified zero-thickness shell model. J Acoust Soc Am 133:1897-910
Chahine, Georges L; Hsiao, Chao-Tsung (2012) MODELING MICROBUBBLE DYNAMICS IN BIOMEDICAL APPLICATIONS(). J Hydrodynam B 24:169-183
Lu, Xiaozhen; Chahine, Georges L; Hsiao, Chao-Tsung (2012) Stability analysis of ultrasound thick-shell contrast agents. J Acoust Soc Am 131:24-34
Moeller, Steen; Yacoub, Essa; Olman, Cheryl A et al. (2010) Multiband multislice GE-EPI at 7 tesla, with 16-fold acceleration using partial parallel imaging with application to high spatial and temporal whole-brain fMRI. Magn Reson Med 63:1144-53
Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges (2010) Three-dimensional modeling of the dynamics of therapeutic ultrasound contrast agents. Ultrasound Med Biol 36:2065-79