Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

[1]  Alexander L. Klibanov,et al.  Microbubble Contrast Agents: Targeted Ultrasound Imaging and Ultrasound-Assisted Drug-Delivery Applications , 2006, Investigative radiology.

[2]  S.W. Smith,et al.  A multiple frequency array for improved diagnostic imaging , 1978, IEEE Transactions on Sonics and Ultrasonics.

[3]  R. Eckersley,et al.  Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power. , 2005, Ultrasound in medicine & biology.

[4]  S. Rhee,et al.  60 MHz PMN-PT based 1-3 composite transducer for IVUS imaging , 2008, 2008 IEEE Ultrasonics Symposium.

[5]  A. Safari,et al.  Perforated pzt-polymer composites for piezoelectric transducer applications , 1982 .

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

[7]  A. Lum,et al.  5A-1 Multi-frequency Array Development for Drug Delivery Therapies: Characterization and First Use of a Triple Row Ultrasound Probe , 2006, 2006 IEEE Ultrasonics Symposium.

[8]  K Kirk Shung,et al.  High Frequency Ultrasonic Imaging. , 2009, Journal of medical ultrasound.

[9]  Jie Chen,et al.  Medical Ultrasonic Transducers With Switchable Frequency Bands Centered About f,,and 2f0 , 1997 .

[10]  K. Ferrara,et al.  A new imaging strategy using wideband transient response of ultrasound contrast agents , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[11]  K. H. Martin,et al.  Current status and prospects for microbubbles in ultrasound theranostics. , 2013, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[12]  E L Ritman,et al.  Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique. , 1998, Journal of the American College of Cardiology.

[13]  Nico de Jong,et al.  A new ultrasonic transducer for improved contrast nonlinear imaging. , 2004, Physics in medicine and biology.

[14]  S. Danforth,et al.  Fabrication of curved ceramic/polymer composite transducer for ultrasonic imaging applications by fused deposition of ceramics , 1998, ISAF 1998. Proceedings of the Eleventh IEEE International Symposium on Applications of Ferroelectrics (Cat. No.98CH36245).

[15]  A. Bouakaz,et al.  Dual-frequency transducer for nonlinear contrast agent imaging , 2012, 2012 IEEE International Ultrasonics Symposium.

[16]  Yaoyao Cui,et al.  A dual-layer micromachined PMN-PT 1-3 composite transducer for broadband ultrasound imaging , 2013, 2013 IEEE International Ultrasonics Symposium (IUS).

[17]  A. Gisolf,et al.  A 20-40 MHz ultrasound transducer for intravascular harmonic imaging , 2004, IEEE Ultrasonics Symposium, 2004.

[18]  H. Chan,et al.  Mode coupling in modified lead titanate/polymer 1–3 composites , 1989 .

[19]  Qifa Zhou,et al.  High-Resolution Acoustic-Radiation-Force-Impulse Imaging for Assessing Corneal Sclerosis , 2013, IEEE Transactions on Medical Imaging.

[20]  F. Stuart Foster,et al.  Hybrid dual frequency transducer and Scanhead for micro-ultrasound imaging , 2009, 2009 IEEE International Ultrasonics Symposium.

[21]  C. Choy,et al.  Single crystal PMN-0.33PT/epoxy 1-3 composites for ultrasonic transducer applications , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[22]  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.

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

[24]  J. Gelly,et al.  A novel acoustic design for dual frequency transducers resulting in separate bandpass for color flow mapping (CFM) , 1990, IEEE Symposium on Ultrasonics.

[25]  John R. Ballard,et al.  Real-Time Implementation of a Dual-Mode Ultrasound Array System: In Vivo Results , 2013, IEEE Transactions on Biomedical Engineering.

[26]  Ronald E. McKeighen,et al.  Design guidelines for medical ultrasonic arrays , 1998, Medical Imaging.

[27]  Paul A Dayton,et al.  Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography. , 2015, Ultrasound in medicine & biology.

[28]  A. Prosperetti,et al.  Physics of acoustic cavitation in liquids: H. G. Flynn’s review 35 years later , 1998 .

[29]  P. Phillips,et al.  Contrast–agent detection and quantification , 2004, European radiology.

[30]  Paul A Dayton,et al.  Evaluation of bias voltage modulation sequence for nonlinear contrast agent imaging using a capacitive micromachined ultrasonic transducer array , 2014, Physics in medicine and biology.

[31]  Jianhua Yin,et al.  Fabrication and performance of high-frequency composite transducers with triangular-pillar geometry , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[32]  F. T. ten Cate,et al.  Super harmonic imaging: a new imaging technique for improved contrast detection. , 2002, Ultrasound in medicine & biology.

[33]  Paul A Dayton,et al.  Tailoring the Size Distribution of Ultrasound Contrast Agents: Possible Method for Improving Sensitivity in Molecular Imaging , 2007, Molecular imaging.

[34]  Richard G P Lopata,et al.  Comparison of one-dimensional and two-dimensional least-squares strain estimators for phased array displacement data. , 2009, Ultrasonic imaging.

[35]  P. Phillips,et al.  Contrast pulse sequences (CPS): imaging nonlinear microbubbles , 2001, 2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263).

[36]  Nico de Jong,et al.  Basic Acoustic Properties of Microbubbles , 2002, Echocardiography.

[37]  Patrick D. Wolf,et al.  Dual-mode IVUS transducer for image-guided brain therapy: preliminary experiments. , 2011, Ultrasound in medicine & biology.

[38]  W. A. Smith,et al.  The application of 1-3 piezocomposites in acoustic transducers , 1990, [Proceedings] 1990 IEEE 7th International Symposium on Applications of Ferroelectrics.

[39]  K W Ferrara,et al.  Noninvasive thermometry assisted by a dual-function ultrasound transducer for mild hyperthermia , 2010, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[40]  Robert E. Newnham,et al.  PZT-epoxy piezoelectric transducers: A simplified fabrication procedure , 1981 .

[41]  J. Cannata,et al.  20 MHz/40 MHz dual element transducers for high frequency harmonic imaging , 2008, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[42]  Charles T. Lancée,et al.  Higher harmonics of vibrating gas-filled microspheres. Part one: simulations , 1994 .

[43]  A. Gisolf,et al.  Transducer for harmonic intravascular ultrasound imaging , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[44]  Hairong Zheng,et al.  A sensitive ultrasonic imaging method for targeted contrast microbubble detection , 2008, 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[45]  M. Legros,et al.  3F-6 Ultra-Wide Bandwidth Array for New Imaging Modalities , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[46]  J. Zagzebski,et al.  Pressure-dependent attenuation in ultrasound contrast agents. , 2002, Ultrasound in medicine & biology.

[47]  A. Ergun,et al.  Efficient array design for sonotherapy , 2008, Physics in medicine and biology.

[48]  Paul A Dayton,et al.  Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies , 2010, Molecular imaging.

[49]  W N McDicken,et al.  The dependence of ultrasound contrast agents backscatter on acoustic pressure: theory versus experiment. , 2002, Ultrasonics.

[50]  E. Boerwinkle,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. , 2003, Circulation.

[51]  Investigation of transmit and receive performance at the fundamental and third harmonic resonance frequency of a medical ultrasound transducer. , 2009, Ultrasonics.

[52]  R. Y. Chiao,et al.  Higher order nonlinear ultrasonic imaging , 1999, 1999 IEEE Ultrasonics Symposium. Proceedings. International Symposium (Cat. No.99CH37027).

[53]  Sheng-Wen Huang,et al.  Thermal strain imaging: a review , 2011, Interface Focus.

[54]  Paul A Dayton,et al.  Mapping microvasculature with acoustic angiography yields quantifiable differences between healthy and tumor-bearing tissue volumes in a rodent model. , 2012, Radiology.

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

[56]  Jianguo Ma,et al.  A preliminary engineering design of intravascular dual-frequency transducers for contrast-enhanced acoustic angiography and molecular imaging , 2014, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[57]  Timothy A. Ritter,et al.  Performance of 50 MHz transducers incorporating fiber composite, PVDF, PbTiO/sub 3/ and LiNbO/sub 3/ , 1999, 1999 IEEE Ultrasonics Symposium. Proceedings. International Symposium (Cat. No.99CH37027).

[58]  C. Prins,et al.  Super-harmonic imaging: development of an interleaved phased-array transducer , 2010, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[59]  Hairong Zheng,et al.  A sensitive TLRH targeted imaging technique for ultrasonic molecular imaging , 2010, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[60]  F. Stuart Foster,et al.  Acoustic Angiography: A New Imaging Modality for Assessing Microvasculature Architecture , 2013, Int. J. Biomed. Imaging.

[61]  Timothy G Leighton,et al.  Review of scattering and extinction cross-sections, damping factors, and resonance frequencies of a spherical gas bubble. , 2011, The Journal of the Acoustical Society of America.

[62]  Carl D. Herickhoff,et al.  Dual-Mode Intracranial Catheter Integrating 3D Ultrasound Imaging and Hyperthermia for Neuro-oncology: Feasibility Study , 2009, Ultrasonic imaging.

[63]  L. Ratsimandresy,et al.  A high bandwidth transducer optimized for harmonic imaging , 2000, 2000 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.00CH37121).

[64]  K. Sharma,et al.  In vivo validation and 3D visualization of broadband ultrasound molecular imaging. , 2013, American journal of nuclear medicine and molecular imaging.

[65]  Ayache Bouakaz,et al.  Second harmonic and subharmonic for non-linear wideband contrast imaging using a capacitive micromachined ultrasonic transducer array. , 2013, Ultrasound in medicine & biology.

[66]  Nico de Jong,et al.  Contrast Harmonic Intravascular Ultrasound: A Feasibility Study for Vasa Vasorum Imaging , 2006, Investigative radiology.

[67]  Mark Borden,et al.  Ultrasound microbubble contrast agents: fundamentals and application to gene and drug delivery. , 2007, Annual review of biomedical engineering.

[68]  J.T. Yen,et al.  A dual-layer transducer array for 3-D rectilinear imaging , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[69]  J. Hossack,et al.  Improving the characteristics of a transducer using multiple piezoelectric layers , 1993, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

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

[71]  Pi Hsien Chang,et al.  Second harmonic imaging and harmonic Doppler measurements with Albunex , 1995, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[72]  W. W. Han,et al.  The Design of Efficient Broad-Band Piezoelectric Transducers , 1978 .

[73]  N. de Jong,et al.  A study of phased array transducer topology for superharmonic imaging , 2010, 2010 IEEE International Ultrasonics Symposium.

[74]  Paul A. Dayton,et al.  Acoustic characterization of contrast-to-tissue ratio and axial resolution for dual-frequency contrast-specific acoustic angiography imaging , 2014, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[75]  Akira Sasaki,et al.  Dual-frequency ultrasound imaging and therapeutic bilaminar array using frequency selective isolation layer , 2010, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[76]  F. Foster,et al.  Ultrasound Transducers for Pulse-Echo Medical Imaging , 1983, IEEE Transactions on Biomedical Engineering.

[77]  Nico De Jong,et al.  Contrast superharmonic imaging: a feasibility study. , 2003, Ultrasound in medicine & biology.

[78]  Reinhardlerch Simulation of Piezoelectric Devices by Two- and Three-Dimensional Finite Elements , 2000 .

[79]  R Gramiak,et al.  Echocardiography of the aortic root. , 1968, Investigative radiology.

[80]  Shinichi Takeuchi,et al.  Development of Ultrasound Transducer with Double-Peak-Type Frequency Characteristics for Harmonic Imaging and Subharmonic Imaging , 2002 .

[81]  Man Nguyen,et al.  7.5 MHz Dual-Layer Transducer Array for 3-D Rectilinear Imaging , 2011, Ultrasonic imaging.

[82]  P. Rafter,et al.  Means for increasing sensitivity in non-linear ultrasound imaging systems , 1997 .

[83]  Talat Uppal,et al.  Tissue harmonic imaging , 2010, Australasian journal of ultrasound in medicine.

[84]  Butrus T. Khuri-Yakub,et al.  Capacitive Micromachined Ultrasonic Transducers: Theory and Technology , 2003 .

[85]  A. Bouakaz,et al.  Exploitation of capacitive micromachined transducers for nonlinear ultrasound imaging , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[86]  A. Needles,et al.  High frequency nonlinear B-scan imaging of microbubble contrast agents , 2005, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[87]  M. Wheatley,et al.  Generation of ultraharmonics in surfactant based ultrasound contrast agents: use and advantages. , 2001, Ultrasonics.

[88]  Qifa Zhou,et al.  Piezoelectric materials for high frequency medical imaging applications: A review , 2007 .

[89]  Jin Chang,et al.  Ultrasound transducer and system for real-time simultaneous therapy and diagnosis for noninvasive surgery of prostate tissue , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[90]  K. Parker,et al.  New approaches to nonlinear diffractive field propagation. , 1991, The Journal of the Acoustical Society of America.

[91]  Antonio Colombo,et al.  From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. , 2003, Circulation.

[92]  C. Chin,et al.  Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[93]  A. Needles,et al.  Fabrication and Performance of a 40-MHz Linear Array Based on a 1-3 Composite with Geometric Elevation Focusing , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[94]  V L Newhouse,et al.  Second harmonic ultrasonic blood perfusion measurement. , 1993, Ultrasound in medicine & biology.

[95]  Werner Lauterborn,et al.  Numerical investigation of nonlinear oscillations of gas bubbles in liquids , 1976 .

[96]  R. Y. Chiao,et al.  Subharmonic Imaging with Microbubble Contrast Agents: Initial Results , 1999, Ultrasonic imaging.

[97]  X. Geng,et al.  5I-1 Microfabrication of Piezoelectric Composite Ultrasound Transducers (PC-MUT) , 2006, 2006 IEEE Ultrasonics Symposium.

[98]  R. Hawes,et al.  High-intensity focused ultrasound. , 1994, Gastrointestinal endoscopy clinics of North America.

[99]  Helen Lai Wa Chan,et al.  Piezoelectric cement-based 1-3 composites , 2005 .

[100]  F Stuart Foster,et al.  A new 15-50 MHz array-based micro-ultrasound scanner for preclinical imaging. , 2009, Ultrasound in medicine & biology.

[101]  Charles T. Lancée,et al.  Higher harmonics of vibrating gas-filled microspheres. Part two: measurements , 1994 .

[102]  P. Yock,et al.  Intravascular ultrasound: novel pathophysiological insights and current clinical applications. , 2001, Circulation.

[103]  H. Chan,et al.  A multifrequency composite ultrasonic transducer system , 1988, IEEE 1988 Ultrasonics Symposium Proceedings..

[104]  G. Kino Acoustic waves : devices, imaging, and analog signal processing , 1987 .

[105]  Paul A Dayton,et al.  High-resolution, high-contrast ultrasound imaging using a prototype dual-frequency transducer: In vitro and in vivo studies , 2010, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[106]  R. Krams,et al.  Intravascular ultrasound tissue harmonic imaging in vivo , 2006, IEEE Ultrasonics Symposium, 2004.

[107]  Douglas N. Stephens,et al.  Spatial and Temporal-Controlled Tissue Heating on a Modified Clinical Ultrasound Scanner for Generating Mild Hyperthermia in Tumors , 2010, IEEE Transactions on Biomedical Engineering.

[108]  B. A. Auld,et al.  Tailoring the Properties of Composite Piezoelectric Materials for Medical Ultrasonic Transducers , 1985, IEEE 1985 Ultrasonics Symposium.

[109]  M. Izumi,et al.  A dual frequency ultrasonic probe for medical applications , 1995, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.