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Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence

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Abstract

Purpose

Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury.

Materials and Methods

Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury.

Results

No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 × 3.1 × 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2).

Conclusions

Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.

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Acknowledgements

The authors would like to acknowledge the HistoSonics R&D team, Jim Bertolina, Jon Cannata, Alex Duryea, Ryan Miller, and Zeljko Mladenovic for developing the pulse sequence evaluated in this study and for technical support during the study.

Funding

This study was funded by HistoSonics, Inc.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave, Madison, WI, 53705, USA

    Katherine C. Longo, Emily A. Knott, John F. Swietlik, Fred T. Lee Jr. & Timothy J. Ziemlewicz

  2. Department of Pathology, University of Wisconsin, Madison, USA

    Rao F. Watson

  3. Department of Biomedical Engineering, University of Wisconsin, Madison, USA

    Fred T. Lee Jr.

  4. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, USA

    Lu Mao

  5. Department of Urology, University of Wisconsin, Madison, USA

    Fred T. Lee Jr.

  6. Department of Biomedical Engineering and Mechanics, Virginia Polytechnic and State University, Blacksburg, USA

    Eli Vlaisavljevich

  7. Division of Interventional Radiology, Department of Radiology, University of Pennsylvania, Philadelphia, USA

    Amanda R. Smolock

  8. Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA

    Zhen Xu

  9. Department of Surgery, University of Michigan, Ann Arbor, USA

    Clifford S. Cho

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  1. Katherine C. Longo
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Corresponding author

Correspondence to Katherine C. Longo.

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Conflict of interest

The authors of this manuscript declare relationships with the following companies: Fred T. Lee Jr., MD—Ethicon, Inc.: Consultant, HistoSonics, Inc.: Board Member, Advisor, Stockholder. Amanda Smolock MD, PhD—HistoSonics, Inc.: Advisor, Stockholder. Eli Vlaisavljevich, PhD—HistoSonics, Inc.: Advisor, Stockholder. Zhen Xu, PhD—HistoSonics, Inc.: Founder, Advisor, Stockholder. Timothy Ziemlewicz, MD—Ethicon, Inc.: Consultant, HistoSonics, Inc.: Advisor, Stockholder.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. Approval was obtained from the Institutional animal use and care committee.

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Longo, K.C., Knott, E.A., Watson, R.F. et al. Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence. Cardiovasc Intervent Radiol 42, 1016–1023 (2019). https://doi.org/10.1007/s00270-019-02215-8

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