The Thresholds and Mechanisms of Tissue Injury by Focused Ultrasound
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Therapeutic ultrasound is used in clinics around the world to treat ailments such as uterine fibroids, kidney stones, and plantar fasciitis. While many of the therapeutic effects of ultrasound are elicited by hyperthermia, bubbles can also interact with tissue to produce beneficial effects. For example, bubbles are used in boiling histotripsy to de-bulk tissue and are used in shock wave lithotripsy to break kidney stones. However, the same bubbles that break the kidney stones also damage the kidney, which is why bubble damage is a concern in every ultrasound application including fetal imaging. Whether the aim is to emulsify a tumor or image a fetus, understanding the thresholds and mechanisms of tissue injury by bubbles in an ultrasound field is important for all ultrasound applications and was the goal of this dissertation. One specific application of therapeutic ultrasound, known as boiling histotripsy, uses shock wave heating to explosively expand a millimeter-size boiling bubble at the transducer focus and fractionate bulk tissue. Yet it was unclear how the millimeter-size boiling or vapor bubble broke down the tissue into its submicron components. In this dissertation, we experimentally tested the hypothesis that ultrasonic atomization, or the emission of fine droplets from an acoustically excited liquid film, is the mechanism by which the millimeter-size boiling bubble in boiling histotripsy fractionates tissue into its submicron components. Using high speed photography, we showed that tissue can behave as a liquid such that a miniature acoustic fountain forms and atomization occurs within a millimeter-size cavity that approximates the boiling or vapor bubble produced by boiling histotripsy. The end result of tissue atomization was a hole in the tissue surface. After showing that tissue can be eroded by atomization, a series of experiments were conducted to determine the tissue properties that influence atomization. The results indicated that highly collagenous tissues such as the liver capsule were difficult to atomize; however it was also shown that surface wetting could be used to enhance atomization by changing the focus of the inverted and reflected ultrasound wave. Finally, the role of bubbles in tissue atomization was investigated using a high static pressure chamber, where it was determined that bubbles are necessary for tissue fractionation. While the investigation into the mechanism of boiling histotripsy was the primary focus of this dissertation, we also established thermal and mechanical injury thresholds for renal tissue injury. This work was driven by the need to determine the safety of a specific therapeutic ultrasound application - renal stone repositioning by ultrasonic propulsion - for FDA approval to begin clinical trials. The end result of this dissertation was an increased understanding of how and at what levels bubbles in an ultrasound field can damage tissue, which is important for developing safe and reliable therapies.
- Bioengineering