Bubble Dynamics and Acoustic Droplet Vaporization in Gas Embolotherapy.

Abstract

Gas embolotherapy is a twist on traditional catheter based embolotherapy approaches. Localized gas bubbles generated are used in place of solid emboli normally used to restrict blood flow. The gas bubbles are formed through targeted vaporization of intravenously injected liquid microdroplets using focused ultrasound, also known as acoustic droplet vaporization (ADV). A greater understanding of the ADV process, bubble transport, and acoustic interactions are essential to devising a safe and effective therapy. This dissertation delves into the dynamics at various time-scales throughout the ADV process from the phase-change process to bubble transport in vessels. The dissertation has been divided into five time-scale events that may occur throughout the ADV process. First, ultra-high speed imaging investigating the initial gas nucleus formation within liquid microdroplets is compared against a numerical model of the acoustic field within the droplet to determine the mechanism behind ADV. The effects of pulse length and acoustic power are correlated with the likelihood of collapsing the newly formed bubble possibly resulting in vessel damage. Next, influences from channel resistance on the ADV bubble expansion rates and wall stress are estimated in idealized microvessels. Once the bubbles have completed expansion, transport phenomena and additional acoustic pulses may influence bubble dynamics and treatment outcomes. The scenario of a finite-sized bubble attached to a vessel wall approaching a bifurcation point is modeled using the boundary element method in order to understand the influences of sticking conditions and bifurcation geometry on bubble lodging or dislodging. Finally, an instability resulting from short acoustic pulses impinging on a bubble attached to a solid boundary resulting in droplet atomization of the bulk liquid in the bubble is characterized. The implications from all of these dynamics are discussed in the context of gas embolotherapy and extended to other ultrasound therapies. It is concluded that potential sources of damage include bubble torus formation, rapid expansion in small vessels, and contact line motion. However, it is revealed that the level of damage can be addressed through the careful choice of acoustic parameters and droplet distribution and functionalization. Furthermore, controlled stress levels can be leveraged for enhanced therapeutic benefits.