Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy

Focused ultrasound offers a non-invasive way of depositing acoustic energy deep into the body, which can be harnessed for a broad spectrum of therapeutic purposes, including tissue ablation, the targeting of therapeutic agents, and stem cell delivery. Phased array transducers enable electronic control over the beam geometry and direction, and can be tailored to provide optimal energy deposition patterns for a given therapeutic application. Their use in combination with modern medical imaging for therapy guidance allows precise targeting, online monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects. In the past there have been some technical obstacles hindering the construction of large aperture, high-power, densely-populated phased arrays and, as a result, they have not been fully exploited for therapy delivery to date. However, recent research has made the construction of such arrays feasible, and it is expected that their continued development will both greatly improve the safety and efficacy of existing ultrasound therapies as well as enable treatments that are not currently possible with existing technology. This review will summarize the basic principles, current statures, and future potential of image-guided ultrasound phased arrays for therapy.

[1]  Kullervo Hynynen,et al.  Invited. Brain edema development after MRI‐guided focused ultrasound treatment , 1998, Journal of magnetic resonance imaging : JMRI.

[2]  V. Rieke,et al.  Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain , 2013, Journal of magnetic resonance imaging : JMRI.

[3]  Alexander L. Klibanov,et al.  Microbubbles in ultrasound-triggered drug and gene delivery. , 2008, Advanced drug delivery reviews.

[4]  K Hynynen,et al.  Thermal effects of focused ultrasound energy on bone tissue. , 2001, Ultrasound in medicine & biology.

[5]  Kwyro Lee,et al.  An ASIC Design for Versatile Receive Front-End Electronics of an Ultrasonic Medical Imaging System — 16 Channel Analog Inputs and 4 Dynamically Focused Beam Outputs , 2003, Ultrasonic imaging.

[6]  Michael D Hill,et al.  Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. , 2004, The New England journal of medicine.

[7]  F A Jolesz,et al.  A clinical, noninvasive, MR imaging-monitored ultrasound surgery method. , 1996, Radiographics : a review publication of the Radiological Society of North America, Inc.

[8]  Ari Partanen,et al.  Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR-guided high-intensity focused ultrasound mediated mild hyperthermia. , 2012, Medical physics.

[9]  Jean-François Aubry,et al.  Transcranial Ultrasonic Therapy Based on Time Reversal of Acoustically Induced Cavitation Bubble Signature , 2010, IEEE Transactions on Biomedical Engineering.

[10]  Kullervo Hynynen,et al.  A new ultrasound method for determining the acoustic phase shifts caused by the skull bone. , 2005, Ultrasound in medicine & biology.

[11]  Jin Woo Chang,et al.  Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes , 2014, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  K. Hynynen,et al.  Thermal dose optimization via temporal switching in ultrasound surgery , 1998, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[13]  C. Cain,et al.  Annular and Sector Phased Array Applicators for Ultrasound Hyperthermia , 1985, IEEE 1985 Ultrasonics Symposium.

[14]  F. Marcus,et al.  The feasibility of using ultrasound for cardiac ablation , 1993, IEEE Transactions on Biomedical Engineering.

[15]  Emad S. Ebbini,et al.  An inverse method for hyperthermia phased-array pattern synthesis , 1988, IEEE 1988 Ultrasonics Symposium Proceedings..

[16]  C. Cain,et al.  Microbubble-enhanced cavitation for noninvasive ultrasound surgery , 2003, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[17]  Nikolitsa Nomikou,et al.  Treating cancer with sonodynamic therapy: A review , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[18]  K Hynynen,et al.  The feasibility of using focused ultrasound for transmyocardial revascularization. , 1998, Ultrasound in medicine & biology.

[19]  K. Hynynen,et al.  High-Intensity Focused Ultrasound (HIFU) for Dissolution of Clots in a Rabbit Model of Embolic Stroke , 2012, PloS one.

[20]  G Wilson Miller,et al.  Ultrashort echo-time MRI versus CT for skull aberration correction in MR-guided transcranial focused ultrasound: In vitro comparison on human calvaria. , 2015, Medical physics.

[21]  Jae-Hun Kim,et al.  Volumetric MR-guided high-intensity focused ultrasound ablation with a one-layer strategy to treat large uterine fibroids: initial clinical outcomes. , 2012, Radiology.

[22]  F. Fry,et al.  Further studies of the transkull transmission of an intense focused ultrasonic beam: lesion production at 500 kHz. , 1980, Ultrasound in medicine & biology.

[23]  Todd Fjield,et al.  Experimental verification of the sectored annular phased array for MRI guided ultrasound surgery , 1996, 1996 IEEE Ultrasonics Symposium. Proceedings.

[24]  Kullervo Hynynen,et al.  Blood-brain barrier: real-time feedback-controlled focused ultrasound disruption by using an acoustic emissions-based controller. , 2012, Radiology.

[25]  G. Haar,et al.  High intensity focused ultrasound--a surgical technique for the treatment of discrete liver tumours. , 1989, Physics in medicine and biology.

[26]  W. O’Brien Ultrasound-biophysics mechanisms. , 2007, Progress in biophysics and molecular biology.

[27]  David Schlesinger,et al.  Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation. , 2015, Journal of neurosurgery.

[28]  J B Fowlkes,et al.  Acoustic droplet vaporization for therapeutic and diagnostic applications. , 2000, Ultrasound in medicine & biology.

[29]  M. Miller,et al.  Erosion of artificial endothelia in vitro by pulsed ultrasound: acoustic pressure, frequency, membrane orientation and microbubble contrast agent dependence. , 1999, Ultrasound in medicine & biology.

[30]  Douglas L. Miller,et al.  The potential for enhancement of mouse melanoma metastasis by diagnostic and high-amplitude ultrasound. , 2006, Ultrasound in medicine & biology.

[31]  J P Donohue,et al.  High intensity focused ultrasound treatment of human BPH. , 1994, Progress in clinical and biological research.

[32]  Toyoaki Uchida,et al.  Improved outcomes with advancements in high intensity focused ultrasound devices for the treatment of localized prostate cancer. , 2015, The Journal of urology.

[33]  J W Hand,et al.  A random phased array device for delivery of high intensity focused ultrasound , 2009, Physics in medicine and biology.

[34]  Shahram Vaezy,et al.  Effects of high‐intensity focused ultrasound on nerve conduction , 2008, Muscle & nerve.

[35]  C. Cain,et al.  Effect of phase errors on field patterns generated by an ultrasound phased-array hyperthermia applicator , 1991, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[36]  K Hynynen,et al.  Design and experimental verification of thin acoustic lenses for the coagulation of large tissue volumes. , 1997, Physics in medicine and biology.

[37]  K. Hynynen,et al.  Transcranial Magnetic Resonance Imaging– Guided Focused Ultrasound Surgery of Brain Tumors: Initial Findings in 3 Patients , 2010, Neurosurgery.

[38]  K. Hynynen,et al.  Transcranial ultrasound focus reconstruction with phase and amplitude correction , 2004, IEEE Ultrasonics Symposium, 2004.

[39]  K. Hynynen,et al.  The design of a focused ultrasound transducer array for the treatment of stroke: a simulation study , 2012, Physics in medicine and biology.

[40]  Kullervo Hynynen,et al.  Drug delivery across the blood–brain barrier using focused ultrasound , 2014, Expert opinion on drug delivery.

[41]  Natalia Vykhodtseva,et al.  Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. , 2012, Ultrasound in medicine & biology.

[42]  Kullervo Hynynen,et al.  A unified model for the speed of sound in cranial bone based on genetic algorithm optimization. , 2002, Physics in medicine and biology.

[43]  K Butts,et al.  Study of focused ultrasound tissue damage using MRI and histology , 1999, Journal of magnetic resonance imaging : JMRI.

[44]  G T Clement,et al.  A non-invasive method for focusing ultrasound through the human skull. , 2002, Physics in medicine and biology.

[45]  N. Smith,et al.  Feasibility of in vivo transesophageal cardiac ablation using a phased ultrasound array. , 2010, Ultrasound in medicine & biology.

[46]  Nathan McDannold,et al.  Transcranial Assessment and Visualization of Acoustic Cavitation: Modeling and Experimental Validation , 2015, IEEE Transactions on Medical Imaging.

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

[48]  J A de Zwart,et al.  Spatial and temporal control of transgene expression in vivo using a heat‐sensitive promoter and MRI‐guided focused ultrasound , 2003, The journal of gene medicine.

[49]  M. A. van den Bosch,et al.  MR-Guided High-Intensity Focused Ultrasound Ablation of Breast Cancer with a Dedicated Breast Platform , 2013, CardioVascular and Interventional Radiology.

[50]  Leslie E. Cross,et al.  Composite Piezoelectric Transducers , 1980 .

[51]  Tim Johansson,et al.  Systematic review of the efficacy and safety of high-intensity focussed ultrasound for the primary and salvage treatment of prostate cancer. , 2010, European urology.

[52]  Guy Vallancien,et al.  Focused Extracorporeal Pyrotherapy: Feasibility Study in Man , 1992 .

[53]  Jongbum Seo,et al.  Anti-foci for focused ultrasound , 2009, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

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

[55]  Bruno Quesson,et al.  Improved Volumetric MR-HIFU Ablation by Robust Binary Feedback Control , 2010, IEEE Transactions on Biomedical Engineering.

[56]  Li Chuan-xing,et al.  High Intensity Focused Ultrasound for the Treatment of Tumors , 2002 .

[57]  P. P. Lele,et al.  Induction of deep, local hyperthermia by ultrasound and electromagnetic fields , 1980, Radiation and environmental biophysics.

[58]  G Montaldo,et al.  Compensating for bone interfaces and respiratory motion in high-intensity focused ultrasound , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[59]  Gregory T. Clement,et al.  Investigation of a large-area phased array for focused ultrasound surgery through the skull. , 2000, Physics in medicine and biology.

[60]  Kim Butts Pauly,et al.  Echo combination to reduce proton resonance frequency (PRF) thermometry errors from fat , 2008, Journal of magnetic resonance imaging : JMRI.

[61]  S. Crouzet,et al.  Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients. , 2014, European urology.

[62]  Hansjörg Hauser,et al.  Latency can be conferred to a variety of cytokines by fusion with latency-associated peptide from TGF-β , 2014, Expert opinion on drug delivery.

[63]  Takuso Sato,et al.  Super‐resolution acoustical passive imaging system using algebraic reconstruction , 1980 .

[64]  C Catalano,et al.  MR-guided focused ultrasound (MRgFUS) ablation for the treatment of nonspinal osteoid osteoma: a prospective multicenter evaluation. , 2014, The Journal of bone and joint surgery. American volume.

[65]  J. Chapelon,et al.  Venous thrombosis generation by means of high-intensity focused ultrasound. , 1995, Ultrasound in medicine & biology.

[66]  Elizabeth A Stewart,et al.  Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. , 2006, Fertility and sterility.

[67]  K Hynynen,et al.  The feasibility of MRI feedback control for intracavitary phased array hyperthermia treatments. , 1998, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[68]  K. Hynynen,et al.  Cylindrical ultrasonic transducers for cardiac catheter ablation , 1997, IEEE Transactions on Biomedical Engineering.

[69]  G. Delso,et al.  Performance Measurements of the Siemens mMR Integrated Whole-Body PET/MR Scanner , 2011, The Journal of Nuclear Medicine.

[70]  S. Maier,et al.  MAGNETIC RESONANCE IMAGING‐GUIDED, HIGH‐INTENSITY FOCUSED ULTRASOUND FOR BRAIN TUMOR THERAPY , 2006, Neurosurgery.

[71]  Joo Ha Hwang,et al.  Histological and biochemical analysis of mechanical and thermal bioeffects in boiling histotripsy lesions induced by high intensity focused ultrasound. , 2013, Ultrasound in medicine & biology.

[72]  F C Vimeux,et al.  Real-time control of focused ultrasound heating based on rapid MR thermometry. , 1999, Investigative radiology.

[73]  Saurabh Datta,et al.  Correlation of cavitation with ultrasound enhancement of thrombolysis. , 2006, Ultrasound in medicine & biology.

[74]  Kullervo Hynynen,et al.  Large improvement of the electrical impedance of imaging and high-intensity focused ultrasound (HIFU) phased arrays using multilayer piezoelectric ceramics coupled in lateral mode , 2012, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[75]  David L. Woods,et al.  Mild hyperthermia with magnetic resonance-guided high-intensity focused ultrasound for applications in drug delivery , 2012, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[76]  Kullervo Hynynen,et al.  Pre-clinical testing of a phased array ultrasound system for MRI-guided noninvasive surgery of the brain--a primate study. , 2006, European journal of radiology.

[77]  J Y Chapelon,et al.  New piezoelectric transducers for therapeutic ultrasound. , 2000, Ultrasound in medicine & biology.

[78]  Vesna Zderic,et al.  Resection of abdominal solid organs using high-intensity focused ultrasound. , 2007, Ultrasound in medicine & biology.

[79]  Yoni Hertzberg,et al.  Ultrasound focusing using magnetic resonance acoustic radiation force imaging: Application to ultrasound transcranial therapy. , 2010, Medical physics.

[80]  Timothy L. Hall,et al.  Removal of residual cavitation nuclei to enhance histotripsy fractionation of soft tissue , 2015, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[81]  Nir Lipsman,et al.  Intracranial Applications of Magnetic Resonance-guided Focused Ultrasound , 2014, Neurotherapeutics.

[82]  E S Ebbini,et al.  Optimization of the intensity gain of multiple-focus phased-array heating patterns. , 1991, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[83]  Aspire Investigators,et al.  Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma , 2015 .

[84]  L. Caplan,et al.  Posterior cerebral artery territory infarcts in the New England Medical Center Posterior Circulation Registry. , 1999, Archives of neurology.

[85]  Junho Song,et al.  Feasibility of Using Lateral Mode Coupling Method for a Large Scale Ultrasound Phased Array for Noninvasive Transcranial Therapy , 2010, IEEE Transactions on Biomedical Engineering.

[86]  J. Barger,et al.  Acoustical properties of the human skull. , 1978, The Journal of the Acoustical Society of America.

[87]  R. Friedlander,et al.  Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. , 2014, Neurosurgery.

[88]  K. Hynynen,et al.  Targeted disruption of the blood–brain barrier with focused ultrasound: association with cavitation activity , 2006, Physics in medicine and biology.

[89]  Kullervo Hynynen,et al.  The application of sparse arrays in high frequency transcranial focused ultrasound therapy: a simulation study. , 2013, Medical physics.

[90]  Zhen Xu,et al.  Cavitation clouds created by shock scattering from bubbles during histotripsy. , 2011, The Journal of the Acoustical Society of America.

[91]  E. Carstensen,et al.  Effects of pulsed ultrasound on the frog heart: I. Thresholds for changes in cardiac rhythm and aortic pressure. , 1993, Ultrasound in medicine & biology.

[92]  Kullervo Hynynen,et al.  Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. , 2007, Radiology.

[93]  A. Hurrell,et al.  Thin-film sparse boundary array design for passive acoustic mapping during ultrasound therapy , 2012, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[94]  Wayne Kreider,et al.  Acoustic holography as a metrological tool for characterizing medical ultrasound sources and fields. , 2015, The Journal of the Acoustical Society of America.

[95]  Kullervo Hynynen,et al.  Ultrasound enhanced drug delivery to the brain and central nervous system , 2012, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[96]  R. Martin,et al.  Control of splenic bleeding by using high intensity ultrasound. , 1999, The Journal of trauma.

[97]  Kullervo Hynynen,et al.  Transcranial passive acoustic mapping with hemispherical sparse arrays using CT-based skull-specific aberration corrections: a simulation study , 2013, Physics in medicine and biology.

[98]  Max Wintermark,et al.  Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound. , 2013, Journal of neurosurgery.

[99]  P. Roberson,et al.  Microbubbles Improve Sonothrombolysis In Vitro and Decrease Hemorrhage In Vivo in a Rabbit Stroke Model , 2011, Investigative radiology.

[100]  E.S. Ebbini,et al.  Direct computation of ultrasound phased-array driving signals from a specified temperature distribution for hyperthermia , 1992, IEEE Transactions on Biomedical Engineering.

[101]  Miklós Gyöngy,et al.  Passive Spatial Mapping of Inertial Cavitation During HIFU Exposure , 2010, IEEE Transactions on Biomedical Engineering.

[102]  W. Tyler,et al.  Transcranial Focused Ultrasound Modulates Intrinsic and Evoked EEG Dynamics , 2014, Brain Stimulation.

[103]  Max Wintermark,et al.  T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound , 2014, Physics in medicine and biology.

[104]  Natalia Vykhodtseva,et al.  Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[105]  E. C. Westerfield,et al.  A Theory of Active Sonar Detection , 1959, Proceedings of the IRE.

[106]  E. Burdette,et al.  Transurethral ultrasound array for prostate thermal therapy: initial studies , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[107]  Kullervo Hynynen,et al.  Uterine leiomyomas: MR imaging-based thermometry and thermal dosimetry during focused ultrasound thermal ablation. , 2006, Radiology.

[108]  R.E. Newnham,et al.  Composite piezoelectric transducer with truncated conical endcaps "cymbal" , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[109]  Zhen Xu,et al.  Transcranial histotripsy therapy: a feasibility study , 2014, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[110]  Jonathan Ophir,et al.  Visualisation of HIFU lesions using elastography of the human prostate in vivo: preliminary results. , 2003, Ultrasound in medicine & biology.

[111]  E E Konofagou,et al.  Harmonic motion imaging for focused ultrasound (HMIFU): a fully integrated technique for sonication and monitoring of thermal ablation in tissues , 2008, Physics in medicine and biology.

[112]  F. Duck,et al.  A review of therapeutic ultrasound: biophysical effects. , 2001, Physical therapy.

[113]  K Hynynen,et al.  Ultrasound surgery using multiple sonications--treatment time considerations. , 1996, Ultrasound in medicine & biology.

[114]  Raffi Bekeredjian,et al.  Ultrasound-Targeted Microbubble Destruction Can Repeatedly Direct Highly Specific Plasmid Expression to the Heart , 2003, Circulation.

[115]  F. Foster,et al.  Development of a 12 element annular array transducer for realtime ultrasound imaging. , 1989, Ultrasound in medicine & biology.

[116]  G. Ehnholm,et al.  Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry. , 2009, Medical physics.

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

[118]  L. Gavrilov,et al.  Application of focused ultrasound for the stimulation of neural structures. , 1996, Ultrasound in medicine & biology.

[119]  J Bercoff,et al.  Monitoring Thermally-Induced Lesions with Supersonic Shear Imaging , 2004, Ultrasonic imaging.

[120]  Rémi Souchon,et al.  The feasibility of tissue ablation using high intensity electronically focused ultrasound , 1993 .

[121]  Stephen J. Norton,et al.  Time exposure acoustics , 2000, IEEE Trans. Geosci. Remote. Sens..

[122]  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.

[123]  J. Dover,et al.  Safety and tolerability of high-intensity focused ultrasonography for noninvasive body sculpting: 24-week data from a randomized, sham-controlled study. , 2012, Aesthetic surgery journal.

[124]  Elisa E Konofagou,et al.  Enhanced Delivery and Bioactivity of the Neurturin Neurotrophic Factor through Focused Ultrasound—Mediated Blood—Brain Barrier Opening in vivo , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[125]  Nadine Barrie Smith,et al.  A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia , 2005, Biomedical engineering online.

[126]  Jürgen Götz,et al.  Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model , 2015, Science Translational Medicine.

[127]  J. Bogousslavsky,et al.  Anterior cerebral artery territory infarction in the Lausanne Stroke Registry. Clinical and etiologic patterns. , 1990, Archives of neurology.

[128]  Ervin B. Podgorsak,et al.  Noninvasive thermometry with a clinical x‐ray CT scanner , 1982 .

[129]  Douglas L. Miller,et al.  Lithotripter shockwave-induced enhancement of mouse melanoma lung metastasis: dependence on cavitation nucleation. , 2004, Journal of endourology.

[130]  Nick Todd,et al.  The effect of electronically steering a phased array ultrasound transducer on near-field tissue heating. , 2011, Medical physics.

[131]  Sabine Ernst,et al.  Pulmonary vein isolation by high-intensity focused ultrasound: first-in-man study with a steerable balloon catheter. , 2007, Heart rhythm.

[132]  C. Cox,et al.  A comparison of the hemolytic potential of Optison and Albunex in whole human blood in vitro: acoustic pressure, ultrasound frequency, donor and passive cavitation detection considerations. , 2001, Ultrasound in medicine & biology.

[133]  K. Hynynen,et al.  Focusing of therapeutic ultrasound through a human skull: a numerical study. , 1998, The Journal of the Acoustical Society of America.

[134]  Kullervo Hynynen,et al.  Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--imaging predictors of success. , 2008, Radiology.

[135]  K Hynynen,et al.  Noninvasive arterial occlusion using MRI-guided focused ultrasound. , 1996, Ultrasound in medicine & biology.

[136]  Ian Rivens,et al.  Quality assurance for clinical high intensity focused ultrasound fields , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[137]  Mathieu Pernot,et al.  Targeting accuracy of transcranial magnetic resonance-guided high-intensity focused ultrasound brain therapy: a fresh cadaver model. , 2013, Journal of neurosurgery.

[138]  J.-L. Thomas,et al.  Ultrasonic beam focusing through tissue inhomogeneities with a time reversal mirror: application to transskull therapy , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[139]  A. E. Miller,et al.  A NEW METHOD FOR THE GENERATION AND USE OF FOCUSED ULTRASOUND IN EXPERIMENTAL BIOLOGY , 1942, The Journal of general physiology.

[140]  L. Crum,et al.  Image-guided acoustic therapy. , 2001, Annual review of biomedical engineering.

[141]  Kullervo Hynynen,et al.  Patterns of thermal deposition in the skull during transcranial focused ultrasound surgery , 2004, IEEE Transactions on Biomedical Engineering.

[142]  C. Holland,et al.  Shaken and stirred: mechanisms of ultrasound-enhanced thrombolysis. , 2015, Ultrasound in medicine & biology.

[143]  K Hynynen,et al.  Low profile lenses for ultrasound surgery , 1998, 1998 IEEE Ultrasonics Symposium. Proceedings (Cat. No. 98CH36102).

[144]  Sun Young Rha,et al.  Pain Palliation in Patients with Bone Metastases Using Magnetic Resonance-Guided Focused Ultrasound with Conformal Bone System: A Preliminary Report , 2015, Yonsei medical journal.

[145]  G. Haar,et al.  High Intensity Focused Ultrasound for the Treatment of Tumors , 2001, Echocardiography.

[146]  C. Song Effect of local hyperthermia on blood flow and microenvironment: a review. , 1984, Cancer research.

[147]  Arik Hananel,et al.  Potential of magnetic resonance-guided focused ultrasound for intracranial hemorrhage: an in vivo feasibility study. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[148]  Rajiv Chopra,et al.  Investigation of power and frequency for 3D conformal MRI-controlled transurethral ultrasound therapy with a dual frequency multi-element transducer , 2012, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[149]  F M Debruyne,et al.  The influence of high-energy shock waves on the development of metastases. , 1996, Ultrasound in medicine & biology.

[150]  Cyril Lafon,et al.  Design and evaluation of a transesophageal HIFU probe for ultrasound-guided cardiac ablation: simulation of a HIFU mini-maze procedure and preliminary ex vivo trials , 2013, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[151]  Michael R. Bailey,et al.  Focused ultrasonic propulsion of kidney stones: review and update of preclinical technology. , 2013, Journal of endourology.

[152]  W J FRY,et al.  Fundamental neurological research and human neurosurgery using intense ultrasound. , 1960, IRE transactions on medical electronics.

[153]  Max Wintermark,et al.  A pilot study of focused ultrasound thalamotomy for essential tremor. , 2013, The New England journal of medicine.

[154]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[155]  John R. Ballard,et al.  Adaptive Transthoracic Refocusing of Dual-Mode Ultrasound Arrays , 2010, IEEE Transactions on Biomedical Engineering.

[156]  Kullervo Hynynen,et al.  MRI-guided ultrasonic heating allows spatial control of exogenous luciferase in canine prostate. , 2005, Ultrasound in medicine & biology.

[157]  K. Hynynen,et al.  Control of the necrosed tissue volume during noninvasive ultrasound surgery using a 16-element phased array. , 1995, Medical physics.

[158]  F. Chavrier,et al.  1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[159]  J. Fandino,et al.  First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound , 2014, Journal of therapeutic ultrasound.

[160]  Chung-Chih Lin,et al.  Design and Experimental Evaluation of a 256-Channel Dual-Frequency Ultrasound Phased-Array System for Transcranial Blood–Brain Barrier Opening and Brain Drug Delivery , 2014, IEEE Transactions on Biomedical Engineering.

[161]  Mickael Tanter,et al.  “Ultrasonic stars” for time-reversal focusing using induced cavitation bubbles , 2006 .

[162]  J A de Zwart,et al.  Fast lipid‐suppressed MR temperature mapping with echo‐shifted gradient‐echo imaging and spectral‐spatial excitation , 1999, Magnetic resonance in medicine.

[163]  K. Hynynen,et al.  A novel, flat, electronically-steered phased array transducer for tissue ablation: preliminary results , 2015, Physics in medicine and biology.

[164]  Kullervo Hynynen,et al.  MRI monitoring of heating produced by ultrasound absorption in the skull: In vivo study in pigs , 2004, Magnetic resonance in medicine.

[165]  F. L. Thurstone,et al.  Sampled Aperture Techniques Applied to B-Mode Echoencephalography , 1975 .

[166]  K Hynynen,et al.  Design and optimization of an aperiodic ultrasound phased array for intracavitary prostate thermal therapies. , 1996, Medical physics.

[167]  Zhen Xu,et al.  Histotripsy methods in mechanical disintegration of tissue: Towards clinical applications , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[168]  Mohamed K. Almekkaway,et al.  Anatomical-based model for simulation of HIFU-induced lesions in atherosclerotic plaques , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[169]  Jean-François Aubry,et al.  Ultrasons focalisés de forte intensité pour la thérapie transcrânienne du cerveau , 2010 .

[170]  Kullervo Hynynen,et al.  Lateral mode coupling to reduce the electrical impedance of small elements required for high power ultrasound therapy phased arrays , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[171]  Mu-Yi Hua,et al.  Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. , 2010, Radiology.

[172]  Gregory T. Clement,et al.  A hemisphere array for non-invasive ultrasound brain therapy and surgery. , 2000, Physics in medicine and biology.

[173]  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.

[174]  Nico de Jong,et al.  Acoustic behavior of microbubbles and implications for drug delivery. , 2014, Advanced drug delivery reviews.

[175]  L A Crum,et al.  Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging. , 2001, Ultrasound in medicine & biology.

[176]  Oliver D Kripfgans,et al.  Towards aberration correction of transcranial ultrasound using acoustic droplet vaporization. , 2008, Ultrasound in medicine & biology.

[177]  Peter A. Lewin,et al.  Transducer characterization using the angular spectrum method , 1989 .

[178]  F A Jolesz,et al.  Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo. , 1996, Ultrasound in medicine & biology.

[179]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[180]  K. Hynynen,et al.  Design and experimental evaluation of an intracavitary ultrasound phased array system for hyperthermia , 1994, IEEE Transactions on Biomedical Engineering.

[181]  Lawrence A Crum,et al.  Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling. , 2011, The Journal of the Acoustical Society of America.

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

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

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

[185]  S. Umemura,et al.  Sonochemical activation of hematoporphyrin: a potential modality for cancer treatment , 1989, Proceedings., IEEE Ultrasonics Symposium,.

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

[187]  Carlo Catalano,et al.  Real-time magnetic resonance-guided high-intensity focused ultrasound focal therapy for localised prostate cancer: preliminary experience. , 2013, European urology.

[188]  Pedro A. Lemos,et al.  Diagnostic Ultrasound Impulses Improve Microvascular Flow in Patients With STEMI Receiving Intravenous Microbubbles. , 2016, Journal of the American College of Cardiology.

[189]  Kullervo Hynynen,et al.  Microbubble contrast agent with focused ultrasound to create brain lesions at low power levels: MR imaging and histologic study in rabbits. , 2006, Radiology.

[190]  Vasant A Salgaonkar,et al.  Passive cavitation imaging with ultrasound arrays. , 2009, The Journal of the Acoustical Society of America.

[191]  M. Fishbein,et al.  Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction. , 2000, Circulation.

[192]  G. Gazelle,et al.  Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. , 2000, AJR. American journal of roentgenology.

[193]  R.E. Caulfield,et al.  A novel phase assignment protocol and driving system for a high-density focused ultrasound array , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[194]  Pei Zhong,et al.  Investigation of HIFU-induced anti-tumor immunity in a murine tumor model , 2007, Journal of Translational Medicine.

[195]  Filippo Crea,et al.  Diagnostic Ultrasound Impulses Improve Microvascular Flow in Patients With STEMI Receiving Intravenous Microbubbles. , 2016, Journal of the American College of Cardiology.

[196]  M Tanter,et al.  Experimental demonstration of noninvasive transskull adaptive focusing based on prior computed tomography scans. , 2003, The Journal of the Acoustical Society of America.

[197]  J Moreno-Moraga,et al.  Body contouring by non‐invasive transdermal focused ultrasound , 2007, Lasers in surgery and medicine.

[198]  Yau-Yau Wai,et al.  Hemorrhage detection during focused-ultrasound induced blood-brain-barrier opening by using susceptibility-weighted magnetic resonance imaging. , 2008, Ultrasound in medicine & biology.

[199]  Kullervo Hynynen,et al.  Simulation study of the effects of near- and far-field heating during focused ultrasound uterine fibroid ablation using an electronically focused phased array: A theoretical analysis of patient safety. , 2014, Medical physics.

[200]  J M Dubernard,et al.  Treatment of prostate cancer with transrectal focused ultrasound: early clinical experience. , 1996, European urology.

[201]  David E Goertz,et al.  Interactions between individual ultrasound-stimulated microbubbles and fibrin clots. , 2014, Ultrasound in medicine & biology.

[202]  Rajiv Chopra,et al.  MRI-controlled transurethral ultrasound therapy for localised prostate cancer , 2010, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[203]  James A. McAteer,et al.  Shock wave lithotripsy: advances in technology and technique , 2009, Nature Reviews Urology.

[204]  Ursula Falkmer,et al.  A Systematic Overview of Radiation Therapy Effects in Skeletal Metastases , 2003, Acta oncologica.

[205]  Kullervo Hynynen,et al.  Frequency considerations for deep ablation with high-intensity focused ultrasound: A simulation study. , 2015, Medical physics.

[206]  Kullervo Hynynen,et al.  Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. , 2014, Radiology.

[207]  S. Baccus,et al.  Precise Neural Stimulation in the Retina Using Focused Ultrasound , 2013, The Journal of Neuroscience.

[208]  A. Bottomley,et al.  Quality of life and symptom end points in palliative bone metastases trials. , 2006, Clinical oncology (Royal College of Radiologists (Great Britain)).

[209]  J. Felmlee,et al.  Assessment of thermal tissue ablation with MR elastography , 2001, Magnetic resonance in medicine.

[210]  K. Hynynen,et al.  Micro-receiver guided transcranial beam steering , 2002, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[211]  K. Hynynen,et al.  Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. , 2001, Radiology.

[212]  Elizabeth A Stewart,et al.  Clinical practice. Uterine fibroids. , 2015, The New England journal of medicine.

[213]  K Hynynen,et al.  A study of various parameters of spherically curved phased arrays for noninvasive ultrasound surgery. , 1996, Physics in medicine and biology.

[214]  J. Poorter,et al.  Noninvasive MRI Thermometry with the Proton Resonance Frequency (PRF) Method: In Vivo Results in Human Muscle , 1995, Magnetic resonance in medicine.

[215]  R. Martin,et al.  Hemostasis of punctured blood vessels using high-intensity focused ultrasound. , 1998, Ultrasound in medicine & biology.

[216]  Nathan McDannold,et al.  Integrated ultrasound and magnetic resonance imaging for simultaneous temperature and cavitation monitoring during focused ultrasound therapies. , 2013, Medical physics.

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

[218]  Kullervo Hynynen,et al.  Comparison of analytical and numerical approaches for CT-based aberration correction in transcranial passive acoustic imaging , 2016, Physics in medicine and biology.

[219]  W. V. Aulock Properties of Phased Arrays , 1960 .

[220]  C. Cain,et al.  Experimental evaluation of a prototype cylindrical section ultrasound hyperthermia phased-array applicator , 1991, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[221]  Kullervo Hynynen,et al.  Multi-frequency characterization of the speed of sound and attenuation coefficient for longitudinal transmission of freshly excised human skulls , 2011, Physics in medicine and biology.

[222]  H. O'neil Theory of Focusing Radiators , 1949 .

[223]  Rajiv Chopra,et al.  Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: Therapeutic effect in rabbit Vx2 tumours , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[224]  Stephen B. Solomon,et al.  Initial Experience with a Novel Focused Ultrasound Ablation System for Ring Ablation Outside the Pulmonary Vein , 2003, Journal of Interventional Cardiac Electrophysiology.

[225]  K. Kuroda,et al.  A precise and fast temperature mapping using water proton chemical shift , 1995, Magnetic resonance in medicine.

[226]  Murad Alam,et al.  Ultrasound skin tightening. , 2014, Dermatologic clinics.

[227]  Amin Nikoozadeh,et al.  First In Vivo Use of a Capacitive Micromachined Ultrasound Transducer Array–Based Imaging and Ablation Catheter , 2012, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[228]  Baudouin Denis de Senneville,et al.  Real‐time adaptive methods for treatment of mobile organs by MRI‐controlled high‐intensity focused ultrasound , 2007, Magnetic resonance in medicine.

[229]  B. Khuri-Yakub,et al.  Characterization of one-dimensional capacitive micromachined ultrasonic immersion transducer arrays , 2001, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[230]  Nathan McDannold,et al.  Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. , 2014, Advanced drug delivery reviews.

[231]  Jeffrey Y. C. Wong,et al.  Focal therapy using magnetic resonance image-guided focused ultrasound in patients with localized prostate cancer , 2016, Journal of therapeutic ultrasound.

[232]  D. Kopelman,et al.  MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[233]  J. Somer Electronic sector scanning for ultrasonic diagnosis. , 1968, Ultrasonics.

[234]  V BELIS,et al.  [HISTOLOGICAL AND BIOCHEMICAL ASPECTS OF SKIN BURNS]. , 1964, Annales de medecine legale, criminologie, police scientifique et toxicologie.

[235]  Kullervo Hynynen,et al.  Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections. , 2015, Medical physics.

[236]  M. A. van den Bosch,et al.  Feasibility of volumetric MRI-guided high intensity focused ultrasound (MR-HIFU) for painful bone metastases , 2014, Journal of therapeutic ultrasound.

[237]  Jørgen Arendt Jensen,et al.  3-D imaging using row–column-addressed arrays with integrated apodization— part ii: transducer fabrication and experimental results , 2015, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[238]  D. King,et al.  Unequally-spaced, broad-band antenna arrays , 1960 .

[239]  K. Hynynen,et al.  Simulations of scanned focused ultrasound hyperthermia. the effects of scanning speed and pattern on the temperature fluctuations at the focal depth , 1988, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[240]  Laura Curiel,et al.  Focused ultrasound treatment of VX2 tumors controlled by local harmonic motion , 2009, Physics in medicine and biology.

[241]  E. Ebbini,et al.  Ultrasound-guided therapeutic focused ultrasound: Current status and future directions , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[242]  Natalia Vykhodtseva,et al.  Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model. , 2016, Journal of neurosurgery.

[243]  P. Wells,et al.  Review: absorption and dispersion of ultrasound in biological tissue. , 1975, Ultrasound in medicine & biology.

[244]  D. Gianfelice,et al.  MR Imaging-guided Focused Ultrasound Surgery of Breast Cancer: Correlation of Dynamic Contrast-enhanced MRI with Histopathologic Findings , 2003, Breast Cancer Research and Treatment.

[245]  Carlo Catalano,et al.  Osteoid osteoma: MR-guided focused ultrasound for entirely noninvasive treatment. , 2013, Radiology.

[246]  Aki Pulkkinen,et al.  The utility of sparse 2D fully electronically steerable focused ultrasound phased arrays for thermal surgery: a simulation study , 2011, Physics in medicine and biology.

[247]  Shy Shoham,et al.  Towards multifocal ultrasonic neural stimulation: pattern generation algorithms , 2010, Journal of neural engineering.

[248]  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.

[249]  K. Hynynen,et al.  The combined concentric-ring and sector-vortex phased array for MRI guided ultrasound surgery , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[250]  D. Certon,et al.  A cMUT probe for ultrasound-guided focused ultrasound targeted therapy , 2015, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[251]  Eleanor Stride,et al.  Properties, characteristics and applications of microbubbles for sonothrombolysis , 2014, Expert opinion on drug delivery.

[252]  Kullervo Hynynen,et al.  MRIgHIFU: A tool for image‐guided therapeutics , 2011, Journal of magnetic resonance imaging : JMRI.

[253]  F A Jolesz,et al.  Thermal effects of focused ultrasound on the brain: determination with MR imaging. , 1997, Radiology.

[254]  R L Magin,et al.  An annular focus ultrasonic lens for local hyperthermia treatment of small tumors. , 1982, Ultrasound in medicine & biology.

[255]  F A Jolesz,et al.  Optimization of chemical shift selective suppression of fat , 1998, Magnetic resonance in medicine.

[256]  E. Schmiedt,et al.  EXTRACORPOREALLY INDUCED DESTRUCTION OF KIDNEY STONES BY SHOCK WAVES , 1980, The Lancet.

[257]  Shahram Vaezy,et al.  Image-guided HIFU neurolysis of peripheral nerves to treat spasticity and pain. , 2004, Ultrasound in medicine & biology.

[258]  A. Gawande Two hundred years of surgery. , 2012, The New England journal of medicine.

[259]  L. S. Smith,et al.  Elevation performance of 1.25D and 1.5D transducer arrays , 1997, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[260]  Richard Bihrle,et al.  High-intensity focused ultrasound , 1995 .

[261]  J. Bernheim,et al.  Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results. , 2000, Circulation.

[262]  Lorena Petrusca,et al.  Experimental investigation of MRgHIFU sonication with interleaved electronic and mechanical displacement of the focal point for transrectal prostate application , 2012, Physics in medicine and biology.

[263]  K. Hynynen,et al.  MRI-guided noninvasive ultrasound surgery. , 1993, Medical physics.

[264]  I. Introductiok,et al.  A Mathematical Theory of Antenna Arrays with Randomly Spaced Elements , 1963 .

[265]  T. Dougherty Photodynamic therapy. , 1993, Photochemistry and photobiology.

[266]  Rajiv Chopra,et al.  Thermometry and ablation monitoring with ultrasound , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[267]  R. Castellani,et al.  Alzheimer disease. , 2010, Disease-a-month : DM.

[268]  Laura Curiel,et al.  MR acoustic radiation force imaging: in vivo comparison to ultrasound motion tracking. , 2009, Medical physics.

[269]  W J FRY,et al.  USE OF INTENSE ULTRASOUND IN NEUROLOGICAL RESEARCH , 1958, American journal of physical medicine.

[270]  Ronald A. Roy,et al.  Temporal and spatial detection of HIFU-induced inertial and hot-vapor cavitation with a diagnostic ultrasound system. , 2009, Ultrasound in medicine & biology.

[271]  H. Jung,et al.  Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study , 2014, Molecular Psychiatry.

[272]  Yun Jing,et al.  Modeling of wave propagation for medical ultrasound: a review , 2015, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[273]  Mickael Tanter,et al.  Attenuation, scattering, and absorption of ultrasound in the skull bone. , 2011, Medical physics.

[274]  S. Alam,et al.  Radiation-force technique to monitor lesions during ultrasonic therapy. , 2003, Ultrasound in medicine & biology.

[275]  Herbert L. Abrams,et al.  An Ultrasonic Phased Array Applicator for Hyperthermia , 1984 .

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

[277]  Rajiv Chopra,et al.  Enhanced drug delivery in rabbit VX2 tumours using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia , 2012, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[278]  M Pernot,et al.  High power transcranial beam steering for ultrasonic brain therapy. , 2003, Physics in medicine and biology.

[279]  M. Livingstone,et al.  Controlled Ultrasound-Induced Blood-Brain Barrier Disruption Using Passive Acoustic Emissions Monitoring , 2012, PloS one.

[280]  K. Hynynen,et al.  Trans-skull ultrasound therapy: the feasibility of using image-derived skull thickness information to correct the phase distortion , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[281]  J A Jensen,et al.  Application of different spatial sampling patterns for sparse array transducer design. , 2000, Ultrasonics.

[282]  Fiona M. Fennessy,et al.  An Update on Magnetic Resonance Guided Focused Ultrasound Surgery (MRgFUS) of Uterine Fibroids , 2013, Current Radiology Reports.

[283]  P. Burns,et al.  Pulse inversion Doppler: a new method for detecting nonlinear echoes from microbubble contrast agents , 1997, 1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118).

[284]  K Hynynen,et al.  The potential of transskull ultrasound therapy and surgery using the maximum available skull surface area. , 1999, The Journal of the Acoustical Society of America.

[285]  E. Unger,et al.  Therapeutic applications of lipid-coated microbubbles. , 2004, Advanced drug delivery reviews.

[286]  Clement,et al.  Field characterization of therapeutic ultrasound phased arrays through forward and backward planar projection , 2000, The Journal of the Acoustical Society of America.

[287]  T. Leighton The Acoustic Bubble , 1994 .

[288]  P. VanBaren,et al.  Ultrasound surgery: comparison of strategies using phased array systems , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[289]  J W Hand,et al.  Development and investigation of ultrasound linear phased arrays for transrectal treatment of prostate. , 1997, Ultrasonics sonochemistry.

[290]  Charles A. Cain,et al.  Concentric-Ring and Sector-Vortex Phased-Array Applicators for Ultrasound Hyperthermia , 1986 .

[291]  W. Gedroyc,et al.  New Clinical Applications of Magnetic Resonance-Guided Focused Ultrasound , 2006, Topics in magnetic resonance imaging : TMRI.

[292]  Natalia Vykhodtseva,et al.  500‐element ultrasound phased array system for noninvasive focal surgery of the brain: A preliminary rabbit study with ex vivo human skulls , 2004, Magnetic resonance in medicine.

[293]  Lars Michels,et al.  Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. , 2012, Neurosurgical focus.

[294]  Fergus V Gleeson,et al.  Contrast-enhanced ultrasound assessment of tissue response to high-intensity focused ultrasound. , 2004, Ultrasound in medicine & biology.

[295]  C. Francis,et al.  Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. , 1995, Ultrasound in medicine & biology.

[296]  D. Parker,et al.  Design and characterization of a laterally mounted phased-array transducer breast-specific MRgHIFU device with integrated 11-channel receiver array. , 2012, Medical physics.

[297]  Daniel Jeanmonod,et al.  First experience with MR-guided focused ultrasound in the treatment of Parkinson's disease , 2014, Journal of therapeutic ultrasound.

[298]  W. Gedroyc,et al.  MRI-guided focused ultrasound (MRgFUS) to treat facet joint osteoarthritis low back pain—case series of an innovative new technique , 2012, European Radiology.

[299]  K. Hynynen,et al.  New design for an endoesophageal sector- based array for the treatment of atrial fibrillation: a parametric simulation study , 2009, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[300]  Fabrice Marquet,et al.  Non-invasive ultrasonic surgery of the brain in non-human primates. , 2013, The Journal of the Acoustical Society of America.

[301]  A. Sarvazyan,et al.  Biomedical applications of radiation force of ultrasound: historical roots and physical basis. , 2010, Ultrasound in medicine & biology.

[302]  K. Hynynen,et al.  MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study , 2013, The Lancet Neurology.

[303]  Mickael Tanter,et al.  Modelling the impulse diffraction field of shear waves in transverse isotropic viscoelastic medium , 2015, Physics in medicine and biology.

[304]  A. P. Ferreira,et al.  Transcranial magnetic resonance guided focused ultrasound: neurosurgery applications , 2014 .

[305]  J. Stanford,et al.  Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. , 2004, Journal of the National Cancer Institute.

[306]  C. Moonen,et al.  A method for MRI guidance of intercostal high intensity focused ultrasound ablation in the liver. , 2010, Medical physics.

[307]  R. E. Davidsen,et al.  Two-Dimensional Random Arrays for Real Time Volumetric Imaging , 1994, Ultrasonic imaging.

[308]  Wei Lu,et al.  Novel ultrasound method to reposition kidney stones , 2010, Urological Research.

[309]  Wen-zhi Chen,et al.  Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. , 2001, Ultrasound in medicine & biology.

[310]  Y. T. Lo,et al.  A mathematical theory of antenna arrays with randomly spaced elements , 1964 .

[311]  J.L. Volakis,et al.  Two-step hybrid virtual array ray (VAR) technique for focusing through the rib cage , 1998, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[312]  Zhen Xu,et al.  Controlled ultrasound tissue erosion: the role of dynamic interaction between insonation and microbubble activity. , 2005, The Journal of the Acoustical Society of America.

[313]  Floyd Dunn,et al.  An early history of high-intensity focused ultrasound , 2015 .

[314]  E. Tanzi,et al.  Microfocused ultrasound for skin tightening. , 2013, Seminars in cutaneous medicine and surgery.

[315]  N. McDannold Quantitative MRI-based temperature mapping based on the proton resonant frequency shift: Review of validation studies , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[316]  C.A. Cain,et al.  Multiple-focus ultrasound phased-array pattern synthesis: optimal driving-signal distributions for hyperthermia , 1989, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[317]  Gregory T. Clement,et al.  Clinical applications of focused ultrasound—The brain , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

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

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

[320]  M Arditi,et al.  Sonothrombolysis: the contribution of stable and inertial cavitation to clot lysis. , 2015, Ultrasound in medicine & biology.

[321]  Ian Rivens,et al.  The use of a segmented transducer for rib sparing in HIFU treatments. , 2006, Ultrasound in medicine & biology.

[322]  M Fink,et al.  Adaptive focusing for transcranial ultrasound imaging using dual arrays. , 2006, The Journal of the Acoustical Society of America.

[323]  Kullervo Hynynen,et al.  Contrast agent kinetics in the rabbit brain during exposure to therapeutic ultrasound. , 2010, Ultrasound in medicine & biology.

[324]  Chandra M Sehgal,et al.  A review of low-intensity ultrasound for cancer therapy. , 2015, Ultrasound in medicine & biology.

[325]  K Hynynen,et al.  In vivo demonstration of noninvasive thermal surgery of the liver and kidney using an ultrasonic phased array. , 1999, Ultrasound in medicine & biology.

[326]  Jing Chen,et al.  Rapid MR‐ARFI method for focal spot localization during focused ultrasound therapy , 2011, Magnetic resonance in medicine.

[327]  J F Greenleaf,et al.  Artificial cavitation nuclei significantly enhance acoustically induced cell transfection. , 1998, Ultrasound in medicine & biology.

[328]  K. Hynynen,et al.  Focused ultrasound effects on nerve action potential in vitro. , 2009, Ultrasound in medicine & biology.

[329]  Meaghan A. O'Reilly,et al.  A super-resolution ultrasound method for brain vascular mapping. , 2013, Medical physics.

[330]  C. Tempany,et al.  Magnetic Resonance–Guided Focused Ultrasound for Patients With Painful Bone Metastases: Phase III Trial Results , 2014, Journal of the National Cancer Institute.

[331]  Robert J. McGough,et al.  Synthesis of monopolar ultrasound pulses for therapy: The frequency-compounding transducer , 2014, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[332]  Natalia Vykhodtseva,et al.  Temporary disruption of the blood-brain barrier by use of ultrasound and microbubbles: safety and efficacy evaluation in rhesus macaques. , 2012, Cancer research.

[333]  P. V. Yuldashev,et al.  Characterization of a multi-element clinical HIFU system using acoustic holography and nonlinear modeling , 2013, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[334]  R. E. Davidsen,et al.  Two-Dimensional Random Arrays for Real Time Volumetric Imaging , 1994 .

[335]  A. Morel,et al.  High‐intensity focused ultrasound for noninvasive functional neurosurgery , 2009, Annals of neurology.

[336]  Elizabeth A Stewart,et al.  Magnetic Resonance-Guided Focused Ultrasound Surgery , 2010, Seminars in reproductive medicine.

[337]  K. Hynynen,et al.  A 256-element ultrasonic phased array system for the treatment of large volumes of deep seated tissue , 1999, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[338]  Yifei Xing,et al.  The effect of high intensity focused ultrasound treatment on metastases in a murine melanoma model. , 2008, Biochemical and biophysical research communications.

[339]  F A Jolesz,et al.  Demonstration of potential noninvasive ultrasound brain therapy through an intact skull. , 1998, Ultrasound in medicine & biology.

[340]  J-F Aubry,et al.  Transcostal high-intensity-focused ultrasound: ex vivo adaptive focusing feasibility study. , 2008, Physics in medicine and biology.

[341]  Francois Vignon,et al.  Microbubble cavitation imaging , 2013, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[342]  Kullervo Hynynen,et al.  Cavitation-based third ventriculostomy using MRI-guided focused ultrasound Laboratory investigation , 2013 .

[343]  Zhen Xu,et al.  Targeted Lesion Generation Through the Skull Without Aberration Correction Using Histotripsy , 2016, IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.

[344]  K. Hynynen,et al.  Design and evaluation of a feedback based phased array system for ultrasound surgery , 1998, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[345]  Elisa E. Konofagou,et al.  Optimization of the Ultrasound-Induced Blood-Brain Barrier Opening , 2012, Theranostics.

[346]  Raquel Delgado-Mederos,et al.  Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. , 2006, Stroke.

[347]  R M Lang,et al.  Combined Assessment of Myocardial Perfusion and Regional Left Ventricular Function by Analysis of Contrast-Enhanced Power Modulation Images , 2001, Circulation.

[348]  Ronald A. Roy,et al.  Applications of Acoustics and Cavitation to Noninvasive Therapy and Drug Delivery , 2008 .

[349]  J. T. Kouzmanoff,et al.  Sparse random ultrasound phased array for focal surgery , 1996, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[350]  Margaret S Livingstone,et al.  Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain , 2013, Physics in medicine and biology.

[351]  J. G. Lynn,et al.  Histology of Cerebral Lesions Produced by Focused Ultrasound. , 1944, The American journal of pathology.

[352]  J. C. Culbertson,et al.  Characterization of one-dimensional quantum channels in InAs/AlSb , 2002 .

[353]  Ryan M. Jones,et al.  Three-Dimensional Transcranial Ultrasound Imaging of Microbubble Clouds Using a Sparse Hemispherical Array , 2014, IEEE Transactions on Biomedical Engineering.

[354]  K Hynynen,et al.  The Usefulness of a Contrast Agent and Gradient–Recalled Acquisition in a Steady–State Imaging Sequence for Magnetic Resonance Imaging–Guided Noninvasive Ultrasound Surgery , 1994, Investigative radiology.

[355]  David E Goertz,et al.  An overview of the influence of therapeutic ultrasound exposures on the vasculature: High intensity ultrasound and microbubble-mediated bioeffects , 2015, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[356]  Aki Pulkkinen,et al.  Simulations and measurements of transcranial low-frequency ultrasound therapy: skull-base heating and effective area of treatment , 2011, Physics in medicine and biology.

[357]  Stephan E Maier,et al.  MRI‐based thermal dosimetry and diffusion‐weighted imaging of MRI‐guided focused ultrasound thermal ablation of uterine fibroids , 2009, Journal of magnetic resonance imaging : JMRI.

[358]  B. Steinberg,et al.  Comparison between the peak sidelobe of the random array and algorithmically designed aperiodic arrays , 1973 .

[359]  M.S. Ibbini,et al.  A field conjugation method for direct synthesis of hyperthermia phases-array heating patterns , 1989, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[360]  P. Hartemann,et al.  Annular Array Transducer for Deep Acoustic Hyperthermia , 1981 .

[361]  M. Francesca Monn,et al.  High-Intensity Focused Ultrasound , 2016 .