Image-guided non-invasive ultrasound liver ablation using histotripsy: Feasibility study in an in vivo porcine model

Hepatocellular carcinoma is one of the fastest growing cancers worldwide. Histotripsy is a non-invasive ablation method that fractionates soft tissue through the control of acoustic cavitation. In this study, we demonstrate the feasibility of using histotripsy for non-invasive liver ablation. Fourteen ~1cm3 lesions were created in the livers of eight pigs through the intact chest in vivo without using aberration correction. Complete fractionation of liver parenchyma was observed with <;500 μm sharp boundaries. In addition, two larger volumes of 18 cm3 and 60 cm3 were generated within 60 minutes. Histotripsy liver fractionation was self-limited at the boundaries of critical structures including the gallbladder and major vessels. The liver surrounding major vessels was completely fractionated while the vessels remained intact. This work demonstrates that histotripsy is capable of noninvasively fractionating liver tissue while preserving critical anatomical structures within the liver. Results suggest histotripsy has potential for the non-invasive ablation of liver tumors.

[1]  S. Curley Radiofrequency ablation of malignant liver tumors. , 2001, The Oncologist.

[2]  J. Marrero,et al.  An intention‐to‐treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[3]  C. Davis Interventional radiological treatment of hepatocellular carcinoma. , 2010, Cancer control : journal of the Moffitt Cancer Center.

[4]  H. Rhim,et al.  Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies , 2009, Hepatology.

[5]  Shota Yamamoto,et al.  Percutaneous ablation of hepatocellular carcinoma: current status. , 2010, Journal of vascular and interventional radiology : JVIR.

[6]  Zhen Xu,et al.  Therapeutic ultrasound to noninvasively create intracardiac communications in an intact animal model , 2011, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[7]  Zhen Xu,et al.  Imaging feedback of histotripsy treatments using ultrasound shear wave elastography , 2012, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[8]  C. Cain,et al.  The effect of histotripsy on tissues with different mechanical properties , 2011, 2011 IEEE International Ultrasonics Symposium.

[9]  Luigi Solbiati,et al.  Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. , 2003, Radiology.

[10]  Zhen Xu,et al.  Quantitative ultrasound backscatter for pulsed cavitational ultrasound therapy-histotripsy , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[11]  M. Fink,et al.  Optimal transcostal high-intensity focused ultrasound with combined real-time 3D movement tracking and correction , 2011, Physics in medicine and biology.

[12]  E. Patterson,et al.  Radiofrequency ablation of porcine liver in vivo: effects of blood flow and treatment time on lesion size. , 1998, Annals of surgery.

[13]  M. Y. Park,et al.  Preliminary experience using high intensity focused ultrasound for treating liver metastasis from colon and stomach cancer , 2009, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[14]  I. Roberts,et al.  High-intensity focused ultrasound ablation of liver tumours: can radiological assessment predict the histological response? , 2008, The British journal of radiology.

[15]  Hui Zhu,et al.  High-intensity focused ultrasound (HIFU): effective and safe therapy for hepatocellular carcinoma adjacent to major hepatic veins , 2009, European Radiology.

[16]  C. R. Hill,et al.  Effect of blood perfusion on the ablation of liver parenchyma with high-intensity focused ultrasound. , 1993, Physics in medicine and biology.

[17]  J S Lewin,et al.  How does alteration of hepatic blood flow affect liver perfusion and radiofrequency‐induced thermal lesion size in rabbit liver? , 2001, Journal of magnetic resonance imaging : JMRI.

[18]  Jin Hee Jang,et al.  High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications , 2011, Abdominal Imaging.

[19]  C. Cain,et al.  Lesion generation through ribs using histotripsy therapy without aberration correction , 2011, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[20]  J Brian Fowlkes,et al.  Histotripsy: minimally invasive technology for prostatic tissue ablation in an in vivo canine model. , 2008, Urology.

[21]  Adam Shaw,et al.  Focusing of high-intensity ultrasound through the rib cage using a therapeutic random phased array. , 2010, Ultrasound in medicine & biology.

[22]  Mathieu Pernot,et al.  3-D real-time motion correction in high-intensity focused ultrasound therapy. , 2004, Ultrasound in medicine & biology.

[23]  F V Gleeson,et al.  The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population , 2005, British Journal of Cancer.

[24]  Masatoshi Kudo,et al.  Radiofrequency Ablation for Hepatocellular Carcinoma: Updated Review in 2010 , 2010, Oncology.

[25]  C. Cain,et al.  Controlled ultrasound tissue erosion , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[26]  F. Jolesz,et al.  Focused Ultrasound as a Local Therapy for Liver Cancer , 2010, Cancer journal.

[27]  Zhen Xu,et al.  Noninvasive Creation of an Atrial Septal Defect by Histotripsy in a Canine Model , 2010, Circulation.

[28]  R. Parks,et al.  Interstitial ablative techniques for hepatic tumours , 2003, The British journal of surgery.

[29]  N. Izumi Recent advances of radiofrequency ablation for early hepatocellular carcinoma , 2011, Journal of gastroenterology and hepatology.

[30]  L. R. Gavrilov,et al.  Focus splitting associated with propagation of focused ultrasound through the rib cage , 2010, Acoustical physics.

[31]  J. E. Parsons,et al.  Cost-effective assembly of a basic fiber-optic hydrophone for measurement of high-amplitude therapeutic ultrasound fields. , 2006, The Journal of the Acoustical Society of America.

[32]  James Sayre,et al.  Influence of large peritumoral vessels on outcome of radiofrequency ablation of liver tumors. , 2003, Journal of vascular and interventional radiology : JVIR.

[33]  Gregory Maclair,et al.  MR-Guided Thermotherapy of Abdominal Organs Using a Robust PCA-Based Motion Descriptor , 2011, IEEE Transactions on Medical Imaging.

[34]  M Fink,et al.  Ultrasonic focusing through the ribs using the DORT method. , 2009, Medical physics.

[35]  Hong Wang,et al.  Phase aberration correction and motion compensation for ultrasonic hyperthermia phased arrays: experimental results , 1994, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[36]  C. Cain,et al.  Histotripsy fractionation of prostate tissue: local effects and systemic response in a canine model. , 2011, The Journal of urology.

[37]  Wen-Zhi Chen,et al.  Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. , 2004, Ultrasonics sonochemistry.

[38]  Gail ter Haar,et al.  High intensity ultrasound. , 2001 .

[39]  Zhen Xu,et al.  Noninvasive treatment of deep venous thrombosis using pulsed ultrasound cavitation therapy (histotripsy) in a porcine model. , 2011, Journal of vascular and interventional radiology : JVIR.

[40]  Yohan Kim,et al.  Non‐invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model , 2011, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[41]  H. El‐Serag,et al.  Rising incidence of hepatocellular carcinoma in the United States. , 1999, The New England journal of medicine.

[42]  C. Cain,et al.  Histotripsy of the prostate: dose effects in a chronic canine model. , 2009, Urology.

[43]  Takamichi Murakami,et al.  A case of hepatocellular carcinoma treated by MR-guided focused ultrasound ablation with respiratory gating. , 2006, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.

[44]  W. Roberts,et al.  Histotripsy of VX-2 tumor implanted in a renal rabbit model. , 2010, Journal of endourology.

[45]  R K Jain,et al.  Determinants of tumor blood flow: a review. , 1988, Cancer research.

[46]  J. E. Parsons,et al.  Pulsed cavitational ultrasound therapy for controlled tissue homogenization. , 2006, Ultrasound in medicine & biology.

[47]  T. Livraghi,et al.  Treatment Options in Hepatocellular Carcinoma Today , 2011, Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society.

[48]  J Brian Fowlkes,et al.  Pulsed cavitational ultrasound: a noninvasive technology for controlled tissue ablation (histotripsy) in the rabbit kidney. , 2006, The Journal of urology.

[49]  Sébastien Roujol,et al.  Real‐time 3D target tracking in MRI guided focused ultrasound ablations in moving tissues , 2010, Magnetic resonance in medicine.

[50]  D L Morris,et al.  Cryotherapy for liver metastases: A new approach , 1989, The British journal of surgery.

[51]  Eleni Liapi,et al.  Transcatheter and ablative therapeutic approaches for solid malignancies. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  W.D. O'Brien,et al.  Current time-domain methods for assessing tissue motion by analysis from reflected ultrasound echoes-a review , 1993, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[53]  J. Kennedy,et al.  High-intensity Focused Ultrasound Principles, Current Uses, and Potential for the Future , 2006, Ultrasound quarterly.

[54]  Philippe C. Cattin,et al.  3D Organ Motion Prediction for MR-Guided High Intensity Focused Ultrasound , 2011, MICCAI.

[55]  Josepa Ribes,et al.  Primary liver cancer: worldwide incidence and trends. , 2004, Gastroenterology.