Dissertation Defense: Developing Image-Guided Histotripsy for the Non-Invasive Treatment of Osteosarcoma
Dissertation Defense: Developing Image-Guided Histotripsy for the Non-Invasive Treatment of Osteosarcoma
Elliana Rose Vickers
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Therapeutic Ultrasound Lab in Biomedical Engineering and Mechanics, & Tuohy Lab in the Virginia-Maryland College of Veterinary Medicine
April 29, 2026, at 12 p.m.
VetMed VMIA, Classroom 220
About this Dissertation
Osteosarcoma (OS) is the most common primary bone tumor in humans and in dogs, with a high level of biological, clinical, and genetic similarity between the canine and pediatric diseases. As such, canine OS is an excellent model in which to evaluate novel therapies for both human and veterinary OS, where new therapeutics are desperately needed. Functional outcomes and overall survival remains poor in both species despite definitive treatment, with no improvements in decades since the addition of chemotherapy to treatment regimens. Histotripsy is an emerging ablation modality with the potential to address this problem, as the first non-invasive, non-thermal, non-ionizing, and image-guided ablation technique. Histotripsy uses ultra-short, high-pressure focused ultrasound pulses to mechanically disintegrate target tissue via acoustic cavitation and has also been shown to induce immunostimulatory changes in the tumor microenvironment. Histotripsy has shown early promise for the treatment of OS in ex vivo canine samples and in treating small portions of canine OS tumors in vivo, followed by limb amputation. However, additional work is needed to optimize histotripsy for the complete ablation of OS, with a focus on the need for improved imaging in bone tumors and more preclinical work to translate this technology for dogs and humans with OS.
This dissertation furthers the development of image-guided histotripsy for the treatment of OS, using a combination of canine and murine models of OS for maximum translational relevance. The research described herein (1) devises improved imaging and treatment strategies for the complete ablation of canine OS in vivo, (2) investigates ex vivo and preclinical characteristics of histotripsy for OS to improve therapeutic safety and efficacy, and (3) applies histotripsy in combination with immunotherapy for the first time in a clinical setting. The completion of this dissertation will significantly advance our technical capabilities and clinical understanding of histotripsy for OS. Future work will build upon this, focusing on investigating the immune outcomes of the described work and advancing patient-specific treatment paradigms, for the purpose of translating histotripsy into the clinic as a non-invasive, limb-sparing therapy for OS in dogs and humans.
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Gettysburg College, B.S., Biology
Training
Graduate Research Assistant, Therapeutic Ultrasound Lab in Biomedical Engineering and Mechanics, & Tuohy Lab in the Virginia-Maryland College of Veterinary Medicine
Mentors
Eli Vlaisavljevich, Ph.D., Associate Professor, Virginia Tech - Wake Forest School of Biomedical Engineering and Sciences
Joanne Tuohy, DVM, Ph.D., Associate Professor, Surgical Oncology, Virginia-Maryland College of Veterinary Medicine
Committee Members
- Sheryl Coutermarsh-Ott, DVM, Ph.D., DACVP, Associate Clinical Professor, Department of Biomedical Sciences and Pathobiology
- Caitlyn Collins, Ph.D., Assistant Professor, Biomedical Engineering
Publications
- Vickers, E.R., Luong, N., Hay, A., Chitwood, A., Kim, M., Merkle, S., Vander Kooi, S., Ruger, L., Coutermarsh-Ott, S., Soliman, S., Malhotra, G., Chen, W., Anderson, D., Lam, S., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2026, in preparation). The first clinical trial of histotripsy plus combination immunotherapy: Patient outcomes in a canine comparative oncology model of osteosarcoma.
- Vickers, E.R., Ruger, L., Iyer, A., Goldfarb, N., Lu, T., Luong, N., Coutermarsh-Ott, S., Raymond, J., Maxwell, A., Tuohy, J., & Vlaisavljevich, E. (2026, in preparation). Characterizing factors that affect skin temperature during histotripsy treatment of extremity bone tumors through experimental and computational data.
- Vickers, E.R., Ruger, L., Iyer, A., Goldfarb, N., Lu, T., Luong, N., Coutermarsh-Ott, S., Raymond, J., Maxwell, A., Tuohy, J., & Vlaisavljevich, E. (2026, in preparation). Characterizing factors that affect skin temperature during histotripsy treatment of extremity bone tumors through experimental and computational data.
- Achari, P., Vickers, E.R., Hay, A., Ruger, L., Vlaisavljevich, E., Tuohy, J., & Collins, C. (2026, in preparation). Tissue-selective bone tumor ablation with histotripsy preserves whole bone integrity in an orthotopic osteosarcoma murine model.
- Tuohy, J., Issa A., Ngo, L., Fields, D., Vickers, E.R., Ruger, L., Dervisis, N., Vlaisavljevich, E., Senger, R., & Robertson, J. (2026, in preparation). Proof-of-concept: Detection of canine osteosarcoma using Rametrix Urine Molecular Fingerprinting (UMF).
- Hay, A., Ruger, L., Vickers, E.R., Coutermarsh-Ott, S., Vlaisavljevich, E., & Tuohy, J. The immunological and clinical outcomes associated with partial tumor volume ablation with histotripsy in spontaneously occurring canine osteosarcoma: A veterinary clinical trial. (2026, submitted). Scientific Reports.
- Simon, A., Suen, J., Ruger, L., Vickers, E.R., Spivey, C., Grider, D., Eden, K., Casey, J., Maxwell, A., & Vlaisavljevich, E. High-rate single-cycle histotripsy for the non-invasive ablation of uterine fibroids (2026, submitted). Ultrasound in Medicine & Biology.
- Simon, A., Ruger, L., Vickers, E.R., Holmes, L., Macco, A., Coutermarsh-Ott, S., Maxwell, A., & Vlaisavljevich, E. Investigation of high PRF single-cycle histotripsy for rapid tissue ablation (2026, in revision). Ultrasound in Medicine & Biology.
- Vickers, E.R., Hay, A., Lopez, V., Luong, N., Antony Baskar, T., Diodato, J., Sze, A., Ruger, L., Wang, M., Soliman, S., Malhotra, G., Coutermarsh-Ott, S., Rossmeisl, J., Vlaisavljevich, E., & Tuohy, J. (2026, in press). Histotripsy treatment reduces tumor burden and extends survival in an orthotopic mouse model of osteosarcoma. Frontiers in Oncology. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1807753/abstract
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Kett, J., Vander Kooi, S., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2026, in press). The first limb-sparing use of histotripsy for canine osteosarcoma. Scientific Reports. https://doi.org/10.1038/s41598-026-42319-z
- Vickers, E.R., Ruger, L., Coutermarsh-Ott, S., Daniel, G., Allen, S., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2026). MRI for the assessment of histotripsy ablation in a canine osteosarcoma comparative oncology model. Ultrasound in Medicine and Biology, 52(1), 216–222. https://doi.org/10.1016/j.ultrasmedbio.2025.09.017
- Achari, P., Vickers, E.R., Ruger, L., Vlaisavljevich, E., Tuohy, J., & Collins, C. (2026). Assessment of histotripsy as a bone-sparing tumor ablation technique in osteosarcoma tumor-affected limbs. Frontiers in Veterinary Science, 12, 1652469. https://doi.org/10.3389/fvets.2025.1652469
- Hay, A., Simon, A., Ruger, L., Gannon, J., Coutermarsh-Ott, S., Vickers, E.R., Eward, W., Neufeld, N., Vlaisavljevich, E., & Tuohy, J. (2025). Establishing human and canine xenograft murine osteosarcoma models for application of focused ultrasound ablation. Biomedicines, 13(9), 2122. https://doi.org/10.3390/biomedicines13092122
- Vezza, C., Ruger, L., Langman, M., Vickers, E.R., Prada, F., Parker, R., Vlaisavljevich, E., & Rossmeisl, J. (2024). First-in-DOg HISTotripsy for intracranial tumors trial: The FIDOHIST study. Technology in Cancer Research and Treatment, 23, 15330338241285158. https://doi.org/10.1177/15330338241285158
- Hay, A., Vickers, E.R., Patwardhan, M., Allen, I.C., Gannon, J., Ruger, L., Vlaisavljevich, E., & Tuohy, J. (2023). Investigating cell death genetic signatures associated with histotripsy treatment of canine osteosarcoma: An in vitro study. International Journal of Hyperthermia, 40(1), 2279027. https://doi.org/10.1080/02656736.2023.2279027
- Hay, A., Ruger, L., Hsueh, A., Vickers, E.R., Klahn, S., Vlaisavljevich, E., & Tuohy, J. (2023). A review of the development of histotripsy for extremity tumor ablation with a canine comparative oncology model to inform human treatments. International Journal of Hyperthermia, 40(1), 2274802. https://doi.org/10.1080/02656736.2023.2274802
- Ruger, L., Yang, E., Coutermarsh-Ott, S., Vickers, E.R., Gannon, J., Nightengale, M., Hsueh, A., Ciepluch, B., Dervisis, N., Vlaisavljevich, E., & Klahn, S. (2023). Histotripsy ablation for the treatment of feline injection site sarcomas: A first-in-cat in vivo feasibility study. International Journal of Hyperthermia, 40(1), 2210272. https://doi.org/10.1080/02656736.2023.2210272
- Ruger, L., Hay, A., Vickers, E.R., Coutermarsh-Ott, S., Gannon, J., Covell, H., Daniel, G., Laeseke, P., Ziemlewicz, T., Kierski, K., Ciepluch, B., Vlaisavljevich, E., & Tuohy, J. (2023). Characterizing the ablative effects of histotripsy for osteosarcoma: In vivo study in dogs. Cancers, 15(3), 741. https://doi.org/10.3390/cancers15030741
Posters
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Chitwood, A., Kim, M., Coutermarsh-Ott, S., Daniel, G., Allen, S., Ziemlewicz, T., Soliman, S., Malhotra, G., Chen, W., Anderson, D., Lam, S., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2026, March 25). Histotripsy, the first non-invasive, non-thermal, and non-ionizing treatment for osteosarcoma: Findings from canine clinical trials [Poster presentation]. St. Jude Invited National Graduate Student Symposium, Memphis, TN.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, June 21–24). Histotripsy as the first non-invasive treatment for bone cancer: Outcomes from studies in mice and pet dogs with osteosarcoma [Poster presentation]. International Society for Therapeutic Ultrasound 2025 Symposium, Banff, Canada.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Kett, J., Vander Kooi, S., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, May 9). Histotripsy as the first non-invasive treatment for bone cancer: Outcomes from studies in mice and pet dogs with osteosarcoma [Poster presentation]. Virginia-Maryland College of Veterinary Medicine Biomedical and Veterinary Sciences Research Symposium, Blacksburg, VA.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Allen, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, April 29). Focused ultrasound for the treatment of osteosarcoma in a canine comparative oncology model: Findings from veterinary clinical trials [Poster presentation]. American Association for Cancer Research Annual Meeting, Chicago, IL.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Daniel, G., Allen, S., Ziemlewicz, T., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2024, September 17). Histotripsy for the treatment of osteosarcoma: Findings from canine clinical trials of fractionated histotripsy treatments. [Poster presentation]. International Society for Therapeutic Ultrasound 2024 Symposium, Taipei City, Taiwan.
- Vickers, E.R., Hay, A., Ruger, L., Patwardhan, M., Vlaisavljevich, E., & Tuohy, J. (2023, January 18). In vitro and in vivo explorations of histotripsy for the treatment of osteosarcoma. [Poster presentation]. Translational Biology, Medicine, and Health 2023 Winter Student Symposium, Roanoke, VA.
- Hay, A., Vickers, E.R., Hixson, H., Kierski, K., Patwardhan, M., Gannon, J., Ruger, L., Vlaisavljevich, E., & Tuohy, J. (2022, November 3 & 4). An in-vitro model for evaluating the immunomodulatory effects of histotripsy ablation for canine osteosarcoma [Poster presentation]. Histotripsy Symposium 2022, Madison, WI.
- Hay, A., Vickers, E.R., Hixson, H., Kierski, K., Patwardhan, M., Gannon, J., Ruger, L., Vlaisavljevich, E., & Tuohy, J. (2022, October 15). An in-vitro model for evaluating the immunomodulatory effects of histotripsy ablation for canine osteosarcoma [Poster presentation]. Veterinary Cancer Society Annual Conference, Norfolk, VA.
Oral Presentations
- Vickers, E.R., Vlaisavljevich, E., & Tuohy, J. (2026, February 13). Therapeutic ultrasound (histotripsy) for osteosarcoma in pet dogs [Oral presentation]. FORum for Translational RESearch on Sarcomas (FORTRESS), Leuven, Belgium.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Chitwood, A., Kim, M., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Malhotra, G., Soliman, S., Lam, S., Chen, W., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, November 14–15). First use of histotripsy ablation plus immunotherapy in clinical trials: Initial findings in canine osteosarcoma [Oral presentation]. Commonwealth of Virginia Cancer Research Conference 2025, Richmond, VA.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, June 11–12). Histotripsy as the first non-invasive treatment for bone cancer: Outcomes from studies in mice and pet dogs with osteosarcoma [Oral presentation]. Fralin Biomedical Research Institute Cancer Research Center 2025 Symposium, Roanoke, VA.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Daniel, G., Ziemlewicz, T., Soliman, S., Malhotra, G., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2025, March 20). Histotripsy as the first non-invasive treatment for bone cancer: Outcomes from studies in mice and pet dogs with osteosarcoma [Oral presentation]. Virginia Tech Focused Ultrasound Workshop, Blacksburg, VA.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Coutermarsh-Ott, S., Daniel, G., Allen, S., Ziemlewicz, T., Maxwell, A., Vlaisavljevich, E., & Tuohy, J. (2024, June 19). Development of histotripsy for the treatment of osteosarcoma: Findings from canine clinical trials at the Virginia Tech Animal Cancer Care and Research Center. [Oral presentation]. Histotripsy Symposium 2024, Minneapolis, MN.
- Vickers, E.R., Ruger, L., Hay, A., Luong, N., Daniel, G., Coutermarsh-Ott, S., Vlaisavljevich, E., & Tuohy, J. (2023, Dec 2). Initial findings from the first treat-and-leave canine clinical trial of histotripsy for bone tumor ablation. [Oral presentation]. Commonwealth of Virginia Cancer Research Conference 2023, Charlottesville, VA.
- Invited to National Graduate Student Symposium | St. Jude, TN (2026)
- 1st Place Drug Development Presentation | Commonwealth of Virginia Cancer Research Conference, VA (2025)
- Student Award Poster Presentation | ISTU 24th International Symposium, Canada (2025)
- 1st Place Student Lightning Talk Presentation | FBRI Cancer Research Center Symposium, VA (2025)
- Invited Student Speaker | Virginia Tech Focused Ultrasound Workshop, VA (2025)
- Recipient of F31 Fellowship | National Cancer Institute, NIH (2024)
- 1st Place Cancer Therapeutics Presentation | Commonwealth of Virginia Cancer Research Conference, VA (2023)
- Recipient of Graduate Research & Development Program Grant Proposal | Virginia Tech, VA (2023)
- 1st Place Student Poster Presentation | TBMH Winter Student Symposium, VA (2023)
- Outreach Chair | International Society of Therapeutic Ultrasound Student Board (2024–2025)
- Wellness Chair | Roanoke Graduate Student Association (2022–2023)