Ex-vivo HIFU experiments using a 32×32-element CMUT array.

High-intensity focused ultrasound (HIFU) has been used as noninvasive treatment for various diseases. For these therapeutic applications, capacitive micromachined ultrasonic transducers (CMUTs) have advantages that make them potentially preferred transducers over traditional piezoelectric transducers. In this paper, we present the design and the fabrication process of an 8×8-mm2, 32×32-element 2-D CMUT array for HIFU applications. To reduce the system complexity for addressing the 1024 transducer elements, we propose to group the CMUT array elements into eight HIFU channels based on the phase delay from the CMUT element to the targeted focal point. Designed to focus at an 8-mm depth with a 5-MHz exciting frequency, this grouping scheme was realized using a custom application-specific integrated circuit (ASIC). With a 40-V DC bias and a 60-V peak-to-peak AC excitation, the surface pressure was measured 1.2 MPa peak-to-peak and stayed stable for a long enough time to create a lesion. With this DC and AC voltage combination, the measured peak-to-peak output pressure at the focus was 8.5 MPa, which is expected to generate a lesion in a minute according to the temperature simulation. Following ex-vivo tissue experiments successfully demonstrated its capability to make lesions in both bovine muscle and liver tissue.

[1]  Morten Fischer Rasmussen,et al.  Dual-mode integrated circuit for imaging and HIFU with 2-D CMUT arrays , 2015, 2015 IEEE International Ultrasonics Symposium (IUS).

[2]  Amin Nikoozadeh,et al.  Integrated Circuits for Volumetric Ultrasound Imaging With 2-D CMUT Arrays , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[3]  A. Nikoozadeh,et al.  Volumetric real-time imaging using a CMUT ring array , 2012, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[4]  Mario Kupnik,et al.  Fabrication of CMUT Cells with Gold Center Mass for Higher Output Pressure , 2011 .

[5]  M. Dewhirst,et al.  Thresholds for thermal damage to normal tissues: An update , 2011, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[6]  Omer Oralkan,et al.  Capacitive micromachined ultrasonic transducers for medical imaging and therapy , 2011, Journal of micromechanics and microengineering : structures, devices, and systems.

[7]  N. Hijnen,et al.  Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: an in vivo proof-of-concept study. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Z Zhao,et al.  Minimally-invasive thermal ablation of early-stage breast cancer: a systemic review. , 2010, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[9]  Mu-Yi Hua,et al.  Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain , 2010, Proceedings of the National Academy of Sciences.

[10]  Wen-zhi Chen,et al.  Primary bone malignancy: effective treatment with high-intensity focused ultrasound ablation. , 2010, Radiology.

[11]  B. Gostout,et al.  Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids. , 2010, Fertility and sterility.

[12]  Mario Kupnik,et al.  Capacitive Micromachined Ultrasonic Transducers for Therapeutic Ultrasound Applications , 2010, IEEE Transactions on Biomedical Engineering.

[13]  A. Nikoozadeh,et al.  An integrated circuit with transmit beamforming flip-chip bonded to a 2-D CMUT array for 3-D ultrasound imaging , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[14]  Joshua E. Soneson,et al.  A User‐Friendly Software Package for HIFU Simulation , 2009 .

[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]  M. Kupnik,et al.  Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT , 2008, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[17]  C. Lafon,et al.  Dual-mode ultrasound transducer for image-guided interstitial thermal therapy. , 2008, Ultrasound in medicine & biology.

[18]  T. Dubinsky,et al.  High-intensity focused ultrasound: current potential and oncologic applications. , 2008, AJR. American journal of roentgenology.

[19]  N. Shabshin,et al.  Pain Palliation in Patients with Bone Metastases Using MR-Guided Focused Ultrasound Surgery: A Multicenter Study , 2008, Annals of Surgical Oncology.

[20]  A.S. Ergun,et al.  5F-5 An Assessment of the Thermal Efficiency of Capacitive Micromachined Ultrasonic Transducers , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[21]  O. Oralkan,et al.  6F-1 Trench-Isolated CMUT Arrays with a Supporting Frame: Characterization and Imaging Results , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[22]  Guo-Liang Xu,et al.  Complications of high intensity focused ultrasound in patients with recurrent and metastatic abdominal tumors. , 2007, World journal of gastroenterology.

[23]  Constantin Coussios,et al.  High intensity focused ultrasound: Physical principles and devices , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[24]  Anna Rozanova-Pierrat,et al.  Mathematical analysis of Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation , 2006 .

[25]  Sharon Thomsen,et al.  Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. , 2006, Journal of the American College of Surgeons.

[26]  Emad S Ebbini,et al.  Dual-Mode Ultrasound Phased Arrays for Image-Guided Surgery , 2006, Ultrasonic imaging.

[27]  Toyoaki Uchida,et al.  Treatment of localized prostate cancer using high‐intensity focused ultrasound , 2006, BJU international.

[28]  K. Boone,et al.  Effect of skin impedance on image quality and variability in electrical impedance tomography: a model study , 1996, Medical and Biological Engineering and Computing.

[29]  O. Oralkan,et al.  Capacitive micromachined ultrasonic transducers: fabrication technology , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[30]  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.

[31]  J. Kennedy High-intensity focused ultrasound in the treatment of solid tumours , 2005, Nature Reviews Cancer.

[32]  Wen-Zhi Chen,et al.  Extracorporeal high intensity focused ultrasound treatment for patients with breast cancer , 2005, Breast Cancer Research and Treatment.

[33]  Wen-Zhi Chen,et al.  Extracorporeal High Intensity Focused Ultrasound Ablation in the Treatment of Patients with Large Hepatocellular Carcinoma , 2004, Annals of Surgical Oncology.

[34]  I. Ladabaum,et al.  Microfabricated ultrasonic transducers monolithically integrated with high voltage electronics , 2004, IEEE Ultrasonics Symposium, 2004.

[35]  Ping Li,et al.  Loss mechanisms in piezoelectric transducers and its response to stress , 2004, International Conference on Information Acquisition, 2004. Proceedings..

[36]  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.

[37]  F. Gleeson,et al.  High-intensity focused ultrasound for the treatment of liver tumours. , 2004, Ultrasonics.

[38]  O. Oralkan,et al.  Volumetric ultrasound imaging using 2-D CMUT arrays , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[39]  Wen-Zhi Chen,et al.  Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. , 2003, The Journal of urology.

[40]  R.W. Martin,et al.  Water-cooled, high-intensity ultrasound surgical applicators with frequency tracking , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[41]  D. Cranston,et al.  High intensity focused ultrasound: surgery of the future? , 2003, The British journal of radiology.

[42]  Kullervo Hynynen,et al.  MR imaging-guided focused ultrasound surgery of uterine leiomyomas: a feasibility study. , 2003, Radiology.

[43]  Lawrence A. Crum,et al.  Mechanisms of lesion formation in high intensity focused ultrasound therapy , 2003 .

[44]  P. J. Hoopes,et al.  Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia , 2003, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[45]  B. Khuri-Yakub,et al.  Capacitive micromachined ultrasonic transducers: next-generation arrays for acoustic imaging? , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[46]  Jing-zhong Sun,et al.  High-intensity focused ultrasound in patients with late-stage pancreatic carcinoma. , 2002, Chinese Medical Journal.

[47]  J. Debus,et al.  A new noninvasive approach in breast cancer therapy using magnetic resonance imaging-guided focused ultrasound surgery. , 2001, Cancer research.

[48]  James E. Coad,et al.  Lesion formation and visualization using dual-mode ultrasound phased arrays , 2001, 2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263).

[49]  J. Chapelon,et al.  Transrectal High Intensity Focused Ultrasound for the Treatment of Localized Prostate Cancer: Factors Influencing the Outcome , 2001, European Urology.

[50]  F A Jolesz,et al.  MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study. , 2001, Radiology.

[51]  F A Jolesz,et al.  Thermal dosimetry of a focused ultrasound beam in vivo by magnetic resonance imaging. , 1999, Medical physics.

[52]  T. Nelson,et al.  Three-dimensional ultrasound imaging. , 1998, Ultrasound in medicine & biology.

[53]  H. H. Pennes Analysis of tissue and arterial blood temperatures in the resting human forearm. 1948. , 1948, Journal of applied physiology.

[54]  C. Lafon,et al.  Design and preliminary results of an ultrasound applicator for interstitial thermal coagulation. , 1998, Ultrasound in medicine & biology.

[55]  J. Schenck The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds. , 1996, Medical physics.

[56]  M. Marberger,et al.  Effect of high-intensity focused ultrasound on human prostate cancer in vivo. , 1995, Cancer research.

[57]  G. Haar,et al.  Ultrasound focal beam surgery. , 1995 .

[58]  Ferenc A. Jolesz,et al.  MR-guided focused ultrasound surgery. , 1992 .

[59]  J. Jensen,et al.  Calculation of pressure fields from arbitrarily shaped, apodized, and excited ultrasound transducers , 1992, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[60]  F. Fry,et al.  High-intensity focused ultrasound in the treatment of experimental liver cancer. , 1991, Archives of surgery.

[61]  S.W. Smith,et al.  High-speed ultrasound volumetric imaging system. I. Transducer design and beam steering , 1991, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[62]  D.H. Turnbull,et al.  Beam steering with pulsed two-dimensional transducer arrays , 1991, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[63]  J. Wu,et al.  Temperature elevation generated by a focused Gaussian beam of ultrasound. , 1990, Ultrasound in medicine & biology.

[64]  W. Nyborg Solutions of the bio-heat transfer equation. , 1988, Physics in medicine and biology.

[65]  W. Dewey,et al.  Thermal dose determination in cancer therapy. , 1984, International journal of radiation oncology, biology, physics.