Skip to main content
SpringerLink
Log in

Transcostal Histotripsy Ablation in an In Vivo Acute Hepatic Porcine Model

  • Laboratory Investigation
  • Non-Vascular Interventions
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

To determine whether histotripsy can create human-scale transcostal ablations in porcine liver without causing severe thermal wall injuries along the beam path.

Materials and Methods

Histotripsy was applied to the liver using a preclinical prototype robotic system through a transcostal window in six female swine. A 3.0 cm spherical ablation zone was prescribed. Duration of treatment (75 min) was longer than a prior subcostal treatment study (24 min, 15 s) to minimize beam path heating. Animals then underwent contrast-enhanced MRI, necropsy, and histopathology. Images and tissue were analyzed for ablation zone size, shape, completeness of necrosis, and off-target effects.

Results

Ablation zones demonstrated complete necrosis with no viable tissue remaining in 6/6 animals by histopathology. Ablation zone volume was close to prescribed (13.8 ± 1.8 cm3 vs. prescribed 14.1 cm3). Edema was noted in the body wall overlying the ablation on T2 MRI in 5/5 (one animal did not receive MRI), though there was no gross or histologic evidence of injury to the chest wall at necropsy. At gross inspection, lung discoloration in the right lower lobe was present in 5/6 animals (mean size: 1 × 2 × 4 cm) with alveolar hemorrhage, preservation of blood vessels and bronchioles, and minor injuries to pneumocytes noted at histology.

Conclusion

Transcostal hepatic histotripsy ablation appears feasible, effective, and no severe injuries were identified in an acute porcine model when prolonged cooling time is added to minimize body wall heating.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Knavel EM, Brace CL. Tumor ablation: common modalities and general practices. Tech Vasc Interv Radiol. 2013;16:192–200. https://doi.org/10.1053/j.tvir.2013.08.002.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Poon RT, Ng KK, Lam CM, et al. Learning curve for radiofrequency ablation of liver tumors: prospective analysis of initial 100 patients in a tertiary institution. Ann Surg. 2004;239:441–9.

    Article  Google Scholar 

  3. Livraghi T, Solbiati L, Meloni MF, et al. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology. 2003;226:441–51. https://doi.org/10.1148/radiol.2262012198.

    Article  PubMed  Google Scholar 

  4. Parsons JE, Cain CA, Abrams GD, Fowlkes JB. Pulsed cavitational ultrasound therapy for controlled tissue homogenization. Ultrasound Med Biol. 2006;32:115–29. https://doi.org/10.1016/j.ultrasmedbio.2005.09.005.

    Article  PubMed  Google Scholar 

  5. Xu Z, Ludomirsky A, Eun LY, et al. Controlled ultrasound tissue erosion. IEEE Trans Ultrason Ferroelectr Freq Control. 2004;51:726–36.

    Article  Google Scholar 

  6. Vlaisavljevich E, Lin K-W, Maxwell A, et al. Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation. Ultrasound Med Biol. 2015;41:1651–67. https://doi.org/10.1016/j.ultrasmedbio.2015.01.028.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Smolock AR, Cristescu MM, Vlaisavljevich E, et al. Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality: Proof of Concept in a Porcine Liver Model. Radiology. 2018;287:485–93. https://doi.org/10.1148/radiol.2018171544.

    Article  PubMed  Google Scholar 

  8. Longo KC, Knott EA, Watson RF, 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. 2019;42:1016–23. https://doi.org/10.1007/s00270-019-02215-8.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lundt JE, Allen SP, Shi J, et al. Non-invasive, Rapid Ablation of Tissue Volume Using Histotripsy. Ultrasound Med Biol. 2017;43:2834–47. https://doi.org/10.1016/j.ultrasmedbio.2017.08.006.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Knott EAEA, Swietlik JFJF, Longo KCKC, et al. Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results. J Vasc Interv Radiol. 2019;30:1293–302. https://doi.org/10.1016/j.jvir.2019.01.023.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vlaisavljevich E, Kim Y, Allen S, et al. Image-guided non-invasive ultrasound liver ablation using histotripsy: feasibility study in an in vivo porcine model. Ultrasound Med Biol. 2013;39:1398–409. https://doi.org/10.1016/j.ultrasmedbio.2013.02.005.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Roberts WW, Hall TL, Ives K, et al. Pulsed Cavitational Ultrasound: A Noninvasive Technology for Controlled Tissue Ablation (Histotripsy) in the Rabbit Kidney. J Urol. 2006;175:734–8. https://doi.org/10.1016/S0022-5347(05)00141-2.

    Article  PubMed  Google Scholar 

  13. Vlaisavljevich E, Kim Y, Owens G, et al. Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage. Phys Med Biol. 2013;59:253–70. https://doi.org/10.1088/0031-9155/59/2/253PMID-24351722.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hall TL, Kieran K, Ives K, et al. Histotripsy of rabbit renal tissue in vivo: temporal histologic trends. J Endourol. 2007;21:1159–66. https://doi.org/10.1089/end.2007.9915.

    Article  PubMed  Google Scholar 

  15. Vlaisavljevich E, Maxwell A, Mancia L, et al. Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment. Ultrasound Med Biol. 2016;42:2466–77. https://doi.org/10.1016/j.ultrasmedbio.2016.05.018.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lake AM, Xu Z, Wilkinson JE, et al. Renal Ablation by Histotripsy—Does it Spare the Collecting System? J Urol. 2008;179:1150–4. https://doi.org/10.1016/j.juro.2007.10.033.

    Article  CAS  PubMed  Google Scholar 

  17. Roberts WW. Development and translation of histotripsy: current status and future directions. Curr Opin Urol. 2014;24:104–10. https://doi.org/10.1097/MOU.0000000000000001.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kim Y, Vlaisavljevich E, Owens GE, et al. In vivo transcostal histotripsy therapy without aberration correction. Phys Med Biol. 2014;59:2553–68. https://doi.org/10.1088/0031-9155/59/11/2553.

    Article  CAS  PubMed  Google Scholar 

  19. Heerink WJ, de Bock GH, de Jonge GJ, et al. Complication rates of CT-guided transthoracic lung biopsy: meta-analysis. Eur Radiol. 2017;27:138–48. https://doi.org/10.1007/s00330-016-4357-8.

    Article  CAS  PubMed  Google Scholar 

  20. ter Haar G. Acoustic Surgery. Phys Today. 2001;54:29–34. https://doi.org/10.1063/1.1445545.

    Article  Google Scholar 

  21. Yu H, Burke CT. Comparison of Percutaneous Ablation Technologies in the Treatment of Malignant Liver Tumors. Semin Interv Radiol. 2014;31:129–37. https://doi.org/10.1055/s-0034-1373788.

    Article  CAS  Google Scholar 

  22. Quesson B, Merle M, Köhler MO, et al. A method for MRI guidance of intercostal high intensity focused ultrasound ablation in the liver. Med Phys. 2010;37:2533–40. https://doi.org/10.1118/1.3413996.

    Article  PubMed  Google Scholar 

  23. Jung SE, Cho SH, Jang JH, Han J-Y. High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications. Abdom Imaging. 2011;36:185–95. https://doi.org/10.1007/s00261-010-9628-2.

    Article  PubMed  Google Scholar 

  24. Fischer K, Gedroyc W, Jolesz FA. Focused Ultrasound as a Local Therapy for Liver Cancer. Cancer J. 2010;16:118–24. https://doi.org/10.1097/PPO.0b013e3181db7c32.

    Article  PubMed  Google Scholar 

  25. Wu F, Wang Z-B, Chen W-Z, et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrason Sonochem. 2004;11:149–54. https://doi.org/10.1016/j.ultsonch.2004.01.011.

    Article  CAS  PubMed  Google Scholar 

  26. Macoskey JJ, Hall TL, Sukovich JR, et al. Soft-Tissue Aberration Correction for Histotripsy. IEEE Trans Ultrason Ferroelectr Freq Control. 2018;65:2073–85. https://doi.org/10.1109/TUFFC.2018.2872727.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gerhardson T, Sukovich JR, Pandey AS, et al. Catheter Hydrophone Aberration Correction for Transcranial Histotripsy Treatment of Intracerebral Hemorrhage: Proof-of-Concept. IEEE Trans Ultrason Ferroelectr Freq Control. 2017;64:1684–97. https://doi.org/10.1109/TUFFC.2017.2748050.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wang TY, Xu Z, Hall TL, et al. Active focal zone sharpening for high-precision treatment using histotripsy. IEEE Trans Ultrason Ferroelectr Freq Control. 2011;58:305–15. https://doi.org/10.1109/TUFFC.2011.1808.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Li J-J, Xu G-L, Gu M-F, et al. Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors. World J Gastroenterol. 2007;13:2747–51. https://doi.org/10.3748/WJG.V13.I19.2747.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bader KB, Haworth KJ, Maxwell AD, Holland CK. Post Hoc Analysis of Passive Cavitation Imaging for Classification of Histotripsy-Induced Liquefaction in Vitro. IEEE Trans Med Imaging. 2018;37:106–15. https://doi.org/10.1109/TMI.2017.2735238.

    Article  PubMed  Google Scholar 

  31. Anthony GJ, Bollen V, Hendley S, et al. Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo. Phys Med Biol. 2019;64. https://doi.org/10.1088/1361-6560/ab143f.

  32. Hansen PD, Rogers S, Corless CL, et al. Radiofrequency ablation lesions in a pig liver model. J Surg Res. 1999. https://doi.org/10.1006/jsre.1999.5709.

    Article  PubMed  Google Scholar 

  33. Brace CL, Laeseke PF, Sampson LA, et al. Microwave ablation with a single small-gauge triaxial antenna: In vivo porcine liver model. Radiology. 2007;242:435–40. https://doi.org/10.1148/radiol.2422051411.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors of this study would like to acknowledge the HistoSonics R&D team (Josh Stopek PhD, Jon Cannata PhD, Ryan Miller PhD, and Alex Duryea PhD) and the animal anesthesia and care team.

Author information

Authors and Affiliations

  1. Department of Radiology, University of Wiscosin–Madison, E3/311 CSC, 600 Highland Ave, Madison, WI, 53792, USA

    Emily A. Knott, Katherine C. Longo, John F. Swietlik, Annie M. Zlevor, Paul F. Laeseke, Fred T. Lee Jr & Timothy J. Ziemlewicz

  2. Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, 325 Stanger St, Blacksburg, VA, USA

    Eli Vlaisavljevich

  3. Department of Pathology and Laboratory Medicine, University of Wiscosin–Madison, 600 Highland Ave, Madison, WI, USA

    Xaiofei Zhang

  4. Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI, USA

    Zhen Xu & Timothy L. Hall

  5. Department of Medicine, University of Wiscosin–Madison, 600 Highland Ave, Madison, WI, USA

    Allison C. Rodgers

Authors
  1. Emily A. Knott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine C. Longo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eli Vlaisavljevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xaiofei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John F. Swietlik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhen Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Allison C. Rodgers
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Annie M. Zlevor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paul F. Laeseke
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Timothy L. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fred T. Lee Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Timothy J. Ziemlewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy J. Ziemlewicz.

Ethics declarations

Conflict of interest

This study has received funding from HistoSonics, Inc. (Ann Arbor, MI). Author EV is a consultant, stockholder, and receives research support from HistoSonics, Inc. Author ZX is a stockholder and receives research support from HistoSonics, Inc. Author PL is a consultant and stockholder with HistoSonics, Inc., a consultant with NeuWave/Ethicon, Inc., and receives research support from Siemens Healthineers. Author TH is a consultant, stockholder, and receives research support from Histosonics, Inc. Author FL is a consultant, stockholder, receives research support, and is on the board of directors at HistoSonics, Inc., is a consultant with Ethicon, Inc., and has patents and royalties with Medtronic, Inc. Author TZ is a consultant, stockholder, receives research support from HistoSonics, Inc. and is a consultant with Ethicon, Inc.)

Informed consent

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. For this type of study, informed consent is not required. For this type of study, consent for publication is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knott, E.A., Longo, K.C., Vlaisavljevich, E. et al. Transcostal Histotripsy Ablation in an In Vivo Acute Hepatic Porcine Model. Cardiovasc Intervent Radiol 44, 1643–1650 (2021). https://doi.org/10.1007/s00270-021-02914-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-021-02914-1

Keywords

Search

Navigation