Pulsed cavitational ultrasound effects on tissue erosion and fluid transport.

The research described in this thesis is motivated by the desire for minimally invasive or non-invasive treatment of disease in several different tissue types in the body. The efficacy and rate of the controlled ultrasound tissue erosion technique, termed histotripsy, was explored in several different tissue types. It was determined that different thresholds do exist in different tissue types and that erosion rate tends to decrease with increasing Young's Modulus (YM), where the softest tissue eroded significantly faster and the hardest tissue did not erode. Additionally, above the threshold for immediate initiation of erosion, the depth erosion rates are independent of gas saturation and intensity, although the erosion area increases with increasing intensity. This gives an overall increase in the volume erosion rate with increasing intensity for a given tissue. To further explore the fast erosion rate in tissues with extremely low YM, erosion rates of uterus, bladder and intestine were examined. In addition to erosion, fluid uptake was observed in the uterus, bladder and intestine. It was found that fluid could be transported into the porcine uterus in vitro at rates of up to 0.3 Lsec-1m-2 and into the rat uterus in vivo at rates of up to 0.1 Lsec -1m-2. Additionally, there was a trend of decreasing average backscatter power with decreasing uptake. This indicates that like erosion, fluid uptake is a cavitation phenomenon and suggests the potential to use backscatter as a feedback mechanism to determine if fluid uptake is occurring. Finally, because fluid uptake and erosion are observed using the same parameters, it is possible that they are competing effects where one dominates the other, depending on tissue type. This procedure is a potential method for drug delivery and could allow treatments that require that drugs be delivered to a specific area, such as focal endometrial cancer. Finally, an intravital microscopy technique has been developed that may allow for real-time visualization of the effects of the therapeutic ultrasound in vivo. Understanding the mechanism behind both erosion and drug uptake is vital for optimization of either technique. In addition, it may aid in the development of monitoring techniques.Ph.D.Applied SciencesBiomedical engineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126127/2/3237935.pd