Title: “Nonlinear acoustic behaviors of ultrasound contrast agents with lipid-coated monodisperse microbubbles”
Tyrone Porter, PhD – ME (Advisor)
Michael Smith, PhD – BME (Chair)
Dimitrije Stamenovic, PhD – BME
Paul Barbone, PhD – ME
Glynn Holt, PhD – ME
Ultrasound contrast agent (UCA) microbubbles are widely used in ultrasound imaging and therapy due to their unique acoustic properties. The acoustic dynamics of UCAs are affected by many factors, such as UCA size, coating material, and excitation modality. The presence of the encapsulation shell would change the mechanical stiffness, viscosity and also the nonlinear dynamic responses of UCA microbubbles, such as the pressure-dependent resonance, second-, sub-, and ultra-harmonic waves, which might bring new insights into medical ultrasound applications.
In this research, a microfluidic flow-focusing device was fabricated for producing lipid-coated UCA microbubbles population with a narrow size distribution. The pressure-dependent resonance frequencies based on acoustic attenuation technique for monodisperse suspensions of UCA microbubbles with different lipid coatings were measured, and the results confirmed that as the pressure increases, pressure-dependent resonance frequency decreases and then becomes plateau. Theoretically, nonlinear attenuation equations with consideration of non-uniform pressure field generated by the acoustic transmit transducers were developed, which were able to estimate the shell initial surface tension, elasticity and viscosity parameters of a lipid-coated bubble population more accurately than linearized equations.
Besides, a setup of measuring subharmonic scatterings from monodisperse lipid-coated UCA microbubble suspensions was built. Results showed that subharmonic could be excited under low incident acoustic pressure. Unlike free bubbles, the initiation pressure of subharmonic scattering signals (subharmonic threshold) for lipid-coated bubbles was not minimum driven at twice linear resonance frequency but over a range of frequencies between linear resonance frequency and twice linear resonance frequency. Experimental behaviors of lipid-coated bubbles were simulated and explained by the numerical results using the shell parameters derived from the above nonlinear attenuation study. It was found that the subharmonic threshold for the lipid-coated microbubbles almost vanished, and it had little relation with bubble size or lipid coating materials used in this study as long as the initial surface tension of the lipid-coated microbubbles were close to zero.