Histotripsy is a non-invasive, focused ultrasound ablation modality that uses the precise control of acoustic cavitation to disintegrate tissue. Acoustic cavitation is the transient expansion of pre-existing nuclei to dimensions orders of magnitude beyond their original size due to large increases in the tensile (peak-negative) pressure of the medium. The peak-negative pressure required to generate a cavitation bubble is defined as the cavitation threshold. Once the cavitation threshold has been reached by an applied acoustic pressure, the remaining internal pressure of the bubble results in violent expansion. Histotripsy utilizes focused ultrasound to tightly control the region in which the acoustic pressure exceeds the cavitation threshold forming cavitation bubbles within a precise focal volume. The rapid expansion and collapse of the cavitation bubbles cause large deformations to the surrounding medium at high strain rates capable of mechanically disrupting cellular structures. During histotripsy therapy, numerous cavitation events are generated from a single pulse within the tightly bound focus of the transducer, defined as the bubble cloud. The disintegration of the targeted tissue volume occurs from the rapid expansion and collapse of bubble clouds over the course of many pulses. By maneuvering the transducer array through the use of robotics or by electronically steering the focus of the array, volumetric ablation of tissue can be performed non-invasively. Histotripsy was recently granted de novo clearance from the FDA for the ablation of liver cancer establishing its clinical relevancy in the field of medicine. This work is inspired by the amazing impact of this therapy and fulfilled with the desire to expand the knowledge of the underlying mechanics of histotripsy to allow for the treatment of malignancies that have not been previously investigated. This dissertation proposal outlines the development of high-rate, non-invasive ablation of soft and fibrous tissue using single-cycle histotripsy. My Ph.D. thesis is motivated to develop histotripsy for the ablation of larger volumes than previously considered feasible and tissues that are more resistant to histotripsy-induced damage by utilizing high pulse repetition frequencies (PRF). In this work, (1) I propose histotripsy for the ablation of uterine fibroids, which are large, fibrous tumors that would require unsuitably long treatment times using traditional histotripsy methods. To deliver higher doses and treat larger volumes within a clinically relevant treatment time, (2) I investigate the effects of PRF on reiterative bubble cloud dynamics in single-cycle histotripsy, and (3) demonstrate how bubble clouds form under high PRF conditions. In the last chapters of this work, (4-5) I developed a high PRF pulsing strategy that can efficiently ablate large volumes of soft tissue and uterine fibroids. The findings and implications found in this document aim to increase the robustness of histotripsy as a non-invasive ablation therapy for many new applications by developing faster ablations and furthering the understanding of the underlying mechanics of histotripsy at clinically relevant pulsing rates. / Doctor of Philosophy / Histotripsy is a new medical therapy that uses the precise control of acoustic cavitation to destroy tissue. Acoustic cavitation is the rapid expansion and collapse of stable bubbles in a fluid based medium. The pressure required to cause cavitation bubbles is called the cavitation threshold. Once the cavitation threshold has been reached, the bubbles result in a violent expansion and collapse. Histotripsy forms cavitation bubbles within a precise area by utilizing focused ultrasound to tightly control the region in which the acoustic pressure exceeds the cavitation threshold. The rapid expansion and collapse of the cavitation bubbles cause the surrounding medium to push away from the growing bubble causing high stress levels capable of breaking down cellular and other tissue structures. During histotripsy therapy, many cavitation events are generated from a single ultrasound pulse within a tightly bounded focal volume, which we define as the bubble cloud. The destruction of the targeted tissue volume occurs from the rapid expansion and collapse of bubble clouds over the course of many pulses. By moving the bubble cloud, entire tumors can be destroyed without any incisions or implants in the body, completely non-invasive. Histotripsy was recently granted clearance from the FDA for the ablation of liver cancer and is in development for many more applications where the complete removal of malignant tissue is desired. This work is inspired by the amazing impact of this therapy and fulfilled with the desire to expand the knowledge of the underlying mechanics of histotripsy to allow for the treatment of malignancies that have not been previously investigated. This dissertation proposal outlines the development of high-rate, single-cycle histotripsy for the ablation of soft and fibrous tissue. My Ph.D. thesis is motivated to develop histotripsy for the ablation of larger volumes than previously considered feasible and tissues that are more resistant to histotripsy-induced damage by increasing the rate at which the therapy is delivered, or the pulse repetition frequencies (PRF). In this work, (1) I propose histotripsy for the ablation of uterine fibroids, which are large, fibrous tumors that would require really long treatment times using traditional histotripsy methods. To deliver the higher doses necessary to treat fibrous tissues or larger volumes, (2) I investigate the effects of PRF on reiterative bubble cloud dynamics in single-cycle histotripsy in vitro, which has not been previously explored, and (3) demonstrate the difference in how bubble clouds form under high rate pulsing regimes. The results of these experiments were used to (4) develop a high PRF pulsing strategy that can efficiently ablate large volumes of soft tissue. In the final chapter, (5) I apply these high-rate ablation methods to uterine fibroids. The findings and implications found in this document aim to increase the robustness of histotripsy as a non-invasive ablation therapy for many new applications by developing faster ablations and furthering the understanding of the underlying mechanics of histotripsy at clinically relevant pulsing rates.

This paper examines how the reality competition television program American Idol serves to reinforce gendered, racialized and heteronormative stereotypes, particularly for female contestants. Through its "democratic" style of public audience voting, those competitors who not only sing well, but also perform their gender and race to standards which have been deemed by the judges to be appropriate mainstream American culture, prove to be the most successful on the program. Through a content analysis of the show's first four seasons, I find that those female contestants who begin their tenure in the contest by fitting into categories which would be considered stereotypical for their gender and race, and continue to appear and behave in this manner, move farther along in the competition than their peers appear to be more innovative. I also find that while the judges comments suggest that American Idol purports to be looking for someone "unique," the contestants who do well in the competition are in fact not exceptional, but rather fit into "conventional" performances of either white or African American women. Those who present themselves as too different, that is, "deviant" from gendered or racialized performances end up being voted off the show before getting their chance to be crowned American Idol.