BME PhD Prospectus Defense - Qian Li

Title: "Nonlinear behavior of phospholipid coated monodisperse microbubbles" Committee: Tyrone Porter, ME (Advisor, Chair) Michael Smith, BME Dimitrije Stamenovic, BME Paul Barbone, ME Glynn Holt, ME Abstract: Ultrasound contrast agent (UCA) microbubbles are widely used in ultrasonic imaging and therapy due to their unique acoustic properties. The acoustic dynamics of UCA are affected by many factors, such as UCA size, coating material and excitation modality. We described a microfluidic technique for producing lipid coated UCA microbubble population with a narrow size distribution. Using acoustic techniques, we measured the pressure dependent resonance frequency based on acoustic attenuation technique for suspensions of UCA with different sizes. Our results confirmed that as the pressure increases, pressure dependent resonance frequency decreases and then plateaus. A theoretical study was carried out to understand this nonlinear behavior. The results from the study suggest that the initial surface tension dictates how strongly the microbubble resonance frequency depends on excitation pressure. With knowledge of the pressure-dependent resonance frequency, acoustic emissions at subharmonic frequencies was studied as a function of excitation:linear resonance frequency ratio. It has been hypothesized that the pressure threshold for subharmonic emissions is minimized for an excitation:resonance frequency ratio = 2. Preliminary results show that subharmonic can be excited under low incident acoustic pressure. Unlike uncoated microbubbles, the results from the study suggest that the pressure threshold for subharmonic emissions is not at twice the linear resonance frequency. Further simulation results reveal subharmonic saturation and then sudden increase of subharmonic amplitude phenomena as pressure increases, which warrants further experimental validation. Moreover, different exciting signals such as chirp excitation (i.e. frequency sweep) show promise in improving bubble subharmonic behavior numerically, which will be further studied experimentally. Future work will also aim at repeating above experiments and simulation over a larger range of bubble size and different lipid shell compositions.