Histotripsy is a noninvasive mechanical ablation method that uses focused ultrasound to disintegrate target tissues into acellular homogenate through the generation of acoustic cavitation and is currently being developed for numerous clinical applications. Histotripsy uses high-pressure (>10 MPa), short-duration (<15 cycles) pulses to cause the rapid expansion and collapse of nuclei at the focus resulting in large applied stress and strain in the adjacent tissue. At a sufficiently high pressure above the target medium's intrinsic cavitation threshold and an adequate number of applied pulses, cavitation "bubble clouds" create precise lesions with high fidelity to the region of the focus. Despite advances in histotripsy, additional research is still needed to better understand the acoustic cavitation nucleation process and its effects on therapies using focused ultrasound. This understanding is critical to better predict and control pulse dose for more rapid and efficient ablation procedures, to reduce off-target cavitation events for safer focused ultrasound therapies, and to localize ablation for high-precision procedures near critical structures or treatments without active imaging guidance.
In this dissertation, I investigate the nucleation and dynamics of ultrasonically generated acoustic cavitation for novel applications of focused ultrasound. My Ph.D. thesis focuses on (1) investigating the effect of histotripsy pulsing parameters on bubble cloud cavitation nucleation, bubble dynamics, and ablation efficiency, (2) investigating the effect of nuclei characteristics on the threshold for cavitation nucleation and resulting bubble dynamics for therapeutic applications, and (3) developing methods alter select characteristics and dynamics of acoustic cavitation by adjusting pulsing parameters to optimize ablation efficiency in conventional and nanoparticle-mediated histotripsy. The culmination of this thesis will advance our understanding of the nucleation and behavior of acoustic cavitation from pulsed focused ultrasound and develop innovative systems to improve the efficacy, efficiency, and safety of clinical focused ultrasound therapies. / Doctor of Philosophy / Histotripsy is a noninvasive focused ultrasound method that precisely destroys target tissues such as tumors through the acoustic generation of cavitation and is currently being developed for numerous clinical applications. Histotripsy uses high-pressure, short-duration pulsed soundwaves to cause the bubbles to rapidly expand and collapse within a precise region called the focus. This rapid cavitation results in large mechanical strain in the targeted tissue. With increasingly higher pressure, numerous bubbles form in the shape of cavitation "bubble clouds" that create lesions, closely matching their shape, in the target tissue after a sufficient number of pulses have been applied. Despite advances in histotripsy, additional research is still needed to better understand the initiation of the acoustic cavitation process in histotripsy and its effects on focused ultrasound therapies. This understanding is critical to better predict and control ablation procedures, improve procedure efficiency, reduce off-target cavitation events for safer focused ultrasound therapies, and further increase ablation precision for procedures near critical structures or treatments without active image guidance.
In this dissertation, I investigate the initiation, growth, and collapse of ultrasonically generated acoustic cavitation for novel applications of focused ultrasound. My Ph.D. thesis focuses on (1) investigating the effect of histotripsy pulsing parameters on bubble cloud cavitation initiation, bubble growth and collapse, and treatment efficiency, (2) investigating the effect of particle characteristics on the threshold for cavitation initiation and resulting bubble behavior for therapeutic applications, and (3) adjusting pulsing parameters to optimize ablation efficiency in conventional and particle mediated histotripsy. The culmination of this thesis will advance our understanding of the initiation and behavior of acoustic cavitation from pulsed focused ultrasound and develop innovative systems to improve the efficacy, efficiency, and safety of clinically focused ultrasound therapies.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/115596 |
| Date | 23 January 2023 |
| Creators | Edsall, Connor William |
| Contributors | Department of Biomedical Engineering and Mechanics, Vlaisavljevich, Eli, Coutier-Delgosha, Olivier, Hall, Timmy L., Arena, Christopher Brian, Shahab, Shima |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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