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Investigations of the Tissue Mechanical Properties and Susceptibility to Histotripsy-Induced Tissue Ablation for Intra-Abdominal Organs

Histotripsy is a non-thermal, non-invasive, focused ultrasound ablation method that uses acoustic cavitation to mechanically break down tissues [1-8]. Histotripsy is heavily dependent on the mechanical properties of the tissue, allowing it to mechanically ablate tissues of lower mechanical stiffness while preserving the stiffer critical structures [15]. However, the mechanical properties of clinically relevant abdominal tissues and critical structures have not yet been adequately quantified under uniform testing parameters. Previous studies have tested and modeled the tissue selectivity of histotripsy, but these studies have been limited by the lack of mechanical property data available for these tissue types. In addition, there remains a need for additional experimental studies directly comparing the differential treatment doses required to induce histotripsy tissue damage in intra-abdominal tissue types. This thesis investigates the mechanical properties of intra-abdominal tissues under uniaxial tension, the effect of histotripsy treatment dose on intra-abdominal soft tissues and critical structures, and the potential of inducing damage to critical structures along the acoustic path pre-focal to the targeted histotripsy treatment. Results show that there are significant differences between the parenchymal tissues (liver, kidney) and the critical structure (stomach, gallbladder, small intestine, ducts, and vessels) elastic modulus, yield stress, yield strain, post-yield strain, energy to yield, and maximum stress and strain at yield. In general, histology analysis from the histotripsy experiments showed that there was an increase in tissue damage with increasing histotripsy pulses/point for all tissues. Critical structures with higher mechanical strength were more resistant to ablation compared to tissues with lower mechanical strength. Pre-focal studies showed damage to gallbladder and small intestine only in cases in which pre-focal cavitation was observed, while no damage occurred in skin and stomach for any samples treated at varying distances from the bubble cloud. Overall, this work improves our understanding of tissue selectivity of histotripsy and provides mechanical properties measurements for clinically relevant tissues that can be used to improve predictive models of tissue-selective histotripsy treatments. This work can be used in the planning of histotripsy treatments to establish proper margins of safety for treating intra-abdominal tumors. / Master of Science / Histotripsy is a non-invasive cancer treatment that mechanically breaks down tissues by rapidly forming and bursting bubbles within the tumor [1-8]. Histotripsy is heavily dependent on the mechanical properties of the tissue, allowing it to destroy weaker tissues while preserving the stiffer tissues in the surrounding area [15]. The mechanical properties of clinically relevant intra-abdominal tissues have not been quantified under uniform testing parameters. Previous studies have tested and modeled the tissue selectivity of histotripsy, but these studies have been limited by the mechanical property data available. This thesis investigates the mechanical properties of intra-abdominal tissues under tension, the effect of histotripsy treatment dose on intra-abdominal tissue damage, and the damage to critical structures from histotripsy treatment at varying distances from the tissue. Results show that there are significant differences between the liver and kidney mechanical stiffness and strength compared to the other tissues. In general, histology analysis showed that there is an increase in tissue damage with increasing histotripsy dose. Tissues with higher mechanical strength were more resistant to damage at lower doses compared to tissues with lower mechanical strength. Histotripsy damage to critical structures that are along the beam path, set distances in front of the focal point of the cavitation bubble cloud was studied. This study showed damage to gallbladder and small intestine only in cases in which pre-focal cavitation, cavitation bubbles that are not within the focal point of the cloud but are in contact with the tissue, was observed, while no damage occurred in skin and stomach for any samples treated at varying distances from the bubble cloud. Overall, this work improves our understanding of tissue selectivity of histotripsy and provides mechanical properties for clinically relevant tissues that can be used to improve predictive models of tissue-selective histotripsy treatments. This work can be used in the planning of histotripsy treatments to establish proper margins of safety for treating intra-abdominal tumors.

Identiferoai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/115842
Date24 July 2023
CreatorsSchwenker, Hannah Ruth
ContributorsDepartment of Biomedical Engineering and Mechanics, Vlaisavljevich, Eli, Wang, Vincent M., Collins, Caitlyn Jayne
PublisherVirginia Tech
Source SetsVirginia Tech Theses and Dissertation
LanguageEnglish
Detected LanguageEnglish
TypeThesis
FormatETD, application/pdf
RightsIn Copyright, http://rightsstatements.org/vocab/InC/1.0/

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