Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue into an acellular homogenate. Histotripsy applies microsecond-length, high pressure (> 10 MPa) pulses to initiate the rapid expansion and collapse of nuclei in a millimeter-scale focal region, applying large stresses and strains to targeted tissues. The cavitation "bubble cloud" generated during histotripsy treatment can be visualized in real time on ultrasound imaging, assisting with treatment guidance and monitoring. Past studies have demonstrated histotripsy's potential for a variety of applications, but histotripsy has not yet been investigated for superficial musculoskeletal tumor ablation. Additionally, preliminary investigations using histotripsy to ablate brain tumors are underway, but require advanced histotripsy devices capable of overcoming attenuation of the therapeutic ultrasound signal by the skull and rely on MRI for real-time guidance. As a result, open questions remain regarding ultrasound-guided histotripsy for brain tumors. Early evidence also suggests that histotripsy ablation may induce immunogenic changes in the tumor microenvironment. Continued research is needed to explain and corroborate these findings under conditions more immunologically representative of human cancers, such as in large animal models with spontaneous tumors.
This dissertation investigates the safety and feasibility of using ultrasound-guided histotripsy to ablate superficial soft tissue sarcomas (STS), osteosarcomas (OS), and brain tumors and considers the immunological impacts of histotripsy treatment for STS and OS. The research described herein (1) investigates the ability of histotripsy to treat superficial STS tumors in companion animals with spontaneous tumors, (2) investigates the feasibility of treating bone tumors with histotripsy through a series of ex vivo and in vivo studies, and (3) applies histotripsy for the minimally invasive treatment of superficial brain tumors. The completion of this dissertation will provide significant insight into the ability of ultrasound-guided histotripsy to treat novel tumor types (i.e., STS, OS, and brain tumors) and the potential role of histotripsy in veterinary medicine. Future work will build upon the studies detailed in this dissertation to optimize ultrasound-guided histotripsy for the treatment of complete STS, OS, and brain tumors in veterinary and human patients. / Doctor of Philosophy / Histotripsy is a non-invasive focused ultrasound therapy that mechanically breaks down targeted tissues through acoustic cavitation. Histotripsy is currently being developed for a number of clinical applications, including tumor ablation, but its potential for treating many cancer types remains unknown. Histotripsy uses very short, high pressure ultrasound pulses to initiate the nucleation of bubbles in the target region. These bubbles then expand and rapidly collapse to impart large stresses and strains on surrounding tissues, leaving behind only acellular debris. The cavitation "bubble cloud" generated during histotripsy treatment can be visualized on ultrasound imaging, offering real-time treatment guidance and monitoring. Histotripsy has not yet been investigated for superficial musculoskeletal tumor ablation, and preliminary studies using histotripsy to ablate brain tumors are underway, but require advanced histotripsy devices still under development. As a result, open questions remain regarding histotripsy ablation as a treatment for musculoskeletal and brain tumors. Additionally, early evidence suggests that histotripsy ablation may be able to stimulate an immune response, treating not only the targeted tumor but also multifocal or metastatic disease. Continued research is needed to explain and corroborate these findings under conditions more similar to human cancers, such as in large animal models with naturally-occurring tumors.
This dissertation investigates the safety and feasibility of using ultrasound-guided histotripsy to ablate superficial soft tissue sarcomas (STS), osteosarcomas (OS), and brain tumors and considers the immunological impacts of histotripsy treatment for STS and OS. This research (1) investigates the ability of histotripsy to treat superficial STS tumors in companion animals with spontaneous tumors, (2) investigates the feasibility of treating bone tumors with histotripsy through a series of ex vivo and in vivo studies, and (3) applies histotripsy for the minimally invasive treatment of superficial brain tumors. The completion of this dissertation will provide significant insight into the ability of ultrasound-guided histotripsy to treat novel tumor types (i.e., STS, OS, and brain tumors) and the potential role of histotripsy in veterinary medicine. Future work will build upon the studies detailed in this dissertation to optimize ultrasound-guided histotripsy for the treatment of complete STS, OS, and brain tumors in veterinary and human patients.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/115077 |
| Date | 16 May 2023 |
| Creators | Ruger, Lauren N. |
| Contributors | Department of Biomedical Engineering and Mechanics, Vlaisavljevich, Eli, Arena, Christopher Brian, Wang, Vincent M., Tuohy, Joanne, Klahn, Shawna L. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/pdf |
| Rights | Creative Commons Attribution 4.0 International, http://creativecommons.org/licenses/by/4.0/ |
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