Publications by authors named "Oleg A Sapozhnikov"

52 Publications

Ultrastructural Analysis of Volumetric Histotripsy Bio-effects in Large Human Hematomas.

Ultrasound Med Biol 2021 Sep 9;47(9):2608-2621. Epub 2021 Jun 9.

Laboratory for Industrial and Medical Ultrasound, Physics Faculty, M. V. Lomonosov Moscow State University, Moscow, Russian Federation; Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model. Large human hematoma phantoms (85 cc) were formed by recalcifying blood anticoagulated with citrate phosphate dextrose/saline-adenine-glucose-mannitol solution. Typical boiling histotripsy pulses (10 or 2 ms) or hybrid histotripsy pulses using higher-amplitude and shorter pulses (0.4 ms) were delivered at 1% duty cycle while continuously translating the HIFU focus location. Histotripsy exposures were performed under ultrasound guidance with a 1.5-MHz transducer (8-cm aperture, F# = 0.75). The volume of liquefied lesions was determined by ultrasound imaging and gross inspection. Untreated hematoma samples and samples of the liquefied lesions aspirated using a fine needle were analyzed cytologically and ultrastructurally with scanning electron microscopy. All exposures resulted in uniform liquid-filled voids with sharp edges; liquefaction speed was higher for exposures with shorter pulses and higher shock amplitudes at the focus (up to 0.32, 0.68 and 2.62 mL/min for 10-, 2- and 0.4-ms pulses, respectively). Cytological and ultrastructural observations revealed completely homogenized blood cells and fibrin fragments in the lysate. Most of the fibrin fragments were less than 20 μm in length, but a number of fragments were up to 150 μm. The lysate with residual debris of that size would potentially be amenable to fine-needle aspiration without risk for needle clogging in clinical implementation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355095PMC
September 2021

A review on B/A measurement methods with a clinical perspective.

J Acoust Soc Am 2021 04;149(4):2200

Electrical Engineering Department, Faculty of Electrical Engineering, Eindhoven University of Technology, Groene Loper 35612 AE, Eindhoven, The Netherlands.

The nonlinear parameter of ultrasound B/A has shown to be a useful diagnostic parameter, reflecting medium content, structure, and temperature. Despite its recognized values, B/A is not yet used as a diagnostic tool in the clinic due to the limitations of current measurement and imaging techniques. This review presents an extensive and comprehensive overview of the techniques developed for B/A measurement of liquid and liquid-like media (e.g., tissue), identifying the methods that are most promising from a clinical perspective. This work summarizes the progress made in the field and the typical challenges on the way to B/A estimation. Limitations and problems with the current techniques are identified, suggesting directions that may lead to further improvement. Since the basic theory of the physics behind the measurement strategies is presented, it is also suited for a reader who is new to nonlinear ultrasound.
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http://dx.doi.org/10.1121/10.0003627DOI Listing
April 2021

"HIFU Beam:" A Simulator for Predicting Axially Symmetric Nonlinear Acoustic Fields Generated by Focused Transducers in a Layered Medium.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2837-2852. Epub 2021 Aug 27.

"HIFU beam" is a freely available software tool that comprises a MATLAB toolbox combined with a user-friendly interface and binary executable compiled from FORTRAN source code (HIFU beam. (2021). Available: http://limu.msu.ru/node/3555?language=en). It is designed for simulating high-intensity focused ultrasound (HIFU) fields generated by single-element transducers and annular arrays with propagation in flat-layered media that mimic biological tissues. Numerical models incorporated in the simulator include evolution-type equations, either the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation or one-way Westervelt equation, for radially symmetric ultrasound beams in homogeneous and layered media with thermoviscous or power-law acoustic absorption. The software uses shock-capturing methods that allow for simulating strongly nonlinear acoustic fields with high-amplitude shocks. In this article, a general description of the software is given along with three representative simulation cases of ultrasound transducers and focusing conditions typical for therapeutic applications. The examples illustrate major nonlinear wave effects in HIFU fields including shock formation. Two examples simulate propagation in water, involving a single-element source (1-MHz frequency, 100-mm diameter, 90-mm radius of curvature) and a 16-element annular array (3-MHz frequency, 48-mm diameter, and 35-mm radius of curvature). The third example mimics the scenario of a HIFU treatment in a "water-muscle-kidney" layered medium using a source typical for abdominal HIFU applications (1.2-MHz frequency, 120-mm diameter, and radius of curvature). Linear, quasi-linear, and shock-wave exposure protocols are considered. It is intended that "HIFU beam" can be useful in teaching nonlinear acoustics; designing and characterizing high-power transducers; and developing exposure protocols for a wide range of therapeutic applications such as shock-based HIFU, boiling histotripsy, drug delivery, immunotherapy, and others.
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http://dx.doi.org/10.1109/TUFFC.2021.3074611DOI Listing
September 2021

Inertial Cavitation Behaviors Induced by Nonlinear Focused Ultrasound Pulses.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Sep 27;68(9):2884-2895. Epub 2021 Aug 27.

Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
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http://dx.doi.org/10.1109/TUFFC.2021.3073347DOI Listing
September 2021

Holographic extraction of plane waves from an ultrasound beam for acoustic characterization of an absorbing layer of finite dimensions.

J Acoust Soc Am 2021 Jan;149(1):386

Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

For the acoustic characterization of materials, a method is proposed for interpreting experiments with finite-sized transducers and test samples in terms of the idealized situation in which plane waves are transmitted through an infinite plane-parallel layer. The method uses acoustic holography, which experimentally provides complete knowledge of the wave field by recording pressure waveforms at points on a surface intersected by the acoustic beam. The measured hologram makes it possible to calculate the angular spectrum of the beam to decompose the field into a superposition of plane waves propagating in different directions. Because these waves cancel one another outside the beam, the idealized geometry of an infinite layer can be represented by a sample of finite size if its lateral dimensions exceed the width of the acoustic beam. The proposed method relies on holograms that represent the acoustic beam with and without the test sample in the transmission path. The method is described theoretically, and its capabilities are demonstrated experimentally for silicone rubber samples by measuring their frequency-dependent phase velocities and absorption coefficients in the megahertz frequency range.
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http://dx.doi.org/10.1121/10.0003212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816771PMC
January 2021

Bilayer aberration-inducing gel phantom for high intensity focused ultrasound applications.

J Acoust Soc Am 2020 12;148(6):3569

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Aberrations induced by soft tissue inhomogeneities often complicate high-intensity focused ultrasound (HIFU) therapies. In this work, a bilayer phantom made from polyvinyl alcohol hydrogel and ballistic gel was built to mimic alternating layers of water-based and lipid tissues characteristic of an abdominal body wall and to reproducibly distort HIFU fields. The density, sound speed, and attenuation coefficient of each material were measured using a homogeneous gel layer. A surface with random topographical features was designed as an interface between gel layers using a 2D Fourier spectrum approach and replicating different spatial scales of tissue inhomogeneities. Distortion of the field of a 256-element 1.5 MHz HIFU array by the phantom was characterized through hydrophone measurements for linear and nonlinear beam focusing and compared to the corresponding distortion induced by an ex vivo porcine body wall of the same thickness. Both spatial shift and widening of the focal lobe were observed, as well as dramatic reduction in focal pressures caused by aberrations. The results suggest that the phantom produced levels of aberration that are similar to a real body wall and can serve as a research tool for studying HIFU effects as well as for developing algorithms for aberration correction.
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http://dx.doi.org/10.1121/10.0002877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097711PMC
December 2020

A Prototype Therapy System for Boiling Histotripsy in Abdominal Targets Based on a 256-Element Spiral Array.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 May 26;68(5):1496-1510. Epub 2021 Apr 26.

Boiling histotripsy (BH) uses millisecond-long ultrasound (US) pulses with high-amplitude shocks to mechanically fractionate tissue with potential for real-time lesion monitoring by US imaging. For BH treatments of abdominal organs, a high-power multielement phased array system capable of electronic focus steering and aberration correction for body wall inhomogeneities is needed. In this work, a preclinical BH system was built comprising a custom 256-element 1.5-MHz phased array (Imasonic, Besançon, France) with a central opening for mounting an imaging probe. The array was electronically matched to a Verasonics research US system with a 1.2-kW external power source. Driving electronics and software of the system were modified to provide a pulse average acoustic power of 2.2 kW sustained for 10 ms with a 1-2-Hz repetition rate for delivering BH exposures. System performance was characterized by hydrophone measurements in water combined with nonlinear wave simulations based on the Westervelt equation. Fully developed shocks of 100-MPa amplitude are formed at the focus at 275-W acoustic power. Electronic steering capabilities of the array were evaluated for shock-producing conditions to determine power compensation strategies that equalize BH exposures at multiple focal locations across the planned treatment volume. The system was used to produce continuous volumetric BH lesions in ex vivo bovine liver with 1-mm focus spacing, 10-ms pulselength, five pulses/focus, and 1% duty cycle.
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http://dx.doi.org/10.1109/TUFFC.2020.3036580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191454PMC
May 2021

Phase-Aberration Correction for HIFU Therapy Using a Multielement Array and Backscattering of Nonlinear Pulses.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Apr 26;68(4):1040-1050. Epub 2021 Mar 26.

Phase aberrations induced by heterogeneities in body wall tissues introduce a shift and broadening of the high-intensity focused ultrasound (HIFU) focus, associated with decreased focal intensity. This effect is particularly detrimental for HIFU therapies that rely on shock front formation at the focus, such as boiling histotripsy (BH). In this article, an aberration correction method based on the backscattering of nonlinear ultrasound pulses from the focus is proposed and evaluated in tissue-mimicking phantoms. A custom BH system comprising a 1.5-MHz 256-element array connected to a Verasonics V1 engine was used as a pulse/echo probe. Pulse inversion imaging was implemented to visualize the second harmonic of the backscattered signal from the focus inside a phantom when propagating through an aberrating layer. Phase correction for each array element was derived from an aberration-correction method for ultrasound imaging that combines both the beamsum and the nearest neighbor correlation method and adapted it to the unique configuration of the array. The results were confirmed by replacing the target tissue with a fiber-optic hydrophone. Comparing the shock amplitude before and after phase-aberration correction showed that the majority of losses due to tissue heterogeneity were compensated, enabling fully developed shocks to be generated while focusing through aberrating layers. The feasibility of using a HIFU phased-array transducer as a pulse-echo probe in harmonic imaging mode to correct for phase aberrations was demonstrated.
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http://dx.doi.org/10.1109/TUFFC.2020.3030890DOI Listing
April 2021

Biofabrication of a Functional Tubular Construct from Tissue Spheroids Using Magnetoacoustic Levitational Directed Assembly.

Adv Healthc Mater 2020 12 18;9(24):e2000721. Epub 2020 Aug 18.

Laboratory for Biotechnological Research "3D Bioprinting Solutions", Moscow, 115409, Russia.

In traditional tissue engineering, synthetic or natural scaffolds are usually used as removable temporal support, which involves some biotechnology limitations. The concept of "scaffield" approach utilizing the physical fields instead of biomaterial scaffold has been proposed recently. In particular, a combination of intense magnetic and acoustic fields can enable rapid levitational bioassembly of complex-shaped 3D tissue constructs from tissue spheroids at low concentration of paramagnetic agent (gadolinium salt) in the medium. In the current study, the tissue spheroids from human bladder smooth muscle cells (myospheres) are used as building blocks for assembling the tubular 3D constructs. Levitational assembly is accomplished at low concentrations of gadolinium salts in the high magnetic field at 9.5 T. The biofabricated smooth muscle constructs demonstrate contraction after the addition of vasoconstrictive agent endothelin-1. Thus, hybrid magnetoacoustic levitational bioassembly is considered as a new technology platform in the emerging field of formative biofabrication. This novel technology of scaffold-free, nozzle-free, and label-free bioassembly opens a unique opportunity for rapid biofabrication of 3D tissue and organ constructs with complex geometry.
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http://dx.doi.org/10.1002/adhm.202000721DOI Listing
December 2020

Noninvasive acoustic manipulation of objects in a living body.

Proc Natl Acad Sci U S A 2020 07 6;117(29):16848-16855. Epub 2020 Jul 6.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA 98105.

In certain medical applications, transmitting an ultrasound beam through the skin to manipulate a solid object within the human body would be beneficial. Such applications include, for example, controlling an ingestible camera or expelling a kidney stone. In this paper, ultrasound beams of specific shapes were designed by numerical modeling and produced using a phased array. These beams were shown to levitate and electronically steer solid objects (3-mm-diameter glass spheres), along preprogrammed paths, in a water bath, and in the urinary bladders of live pigs. Deviation from the intended path was on average <10%. No injury was found on the bladder wall or intervening tissue.
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http://dx.doi.org/10.1073/pnas.2001779117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382215PMC
July 2020

Modeling of photoelastic imaging of mechanical stresses in transparent solids mimicking kidney stones.

J Acoust Soc Am 2020 06;147(6):3819

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 Northeast 40th Street, Seattle, Washington 98105, USA.

Theoretical and numerical models were developed to calculate the polariscopic integrated light intensity that forms a projection of the dynamic stress within an axisymmetric elastic object. Although the model is general, this paper addressed its application to measurements of stresses in model kidney stones from a burst wave lithotripter for stone fragmentation. The stress was calculated using linear elastic equations, and the light propagation was modeled in the instantaneous case by integrating over the volume of the stone. The numerical model was written in finite differences. The resulting images agreed well with measured images. The measured images corresponded to the maximum shear stress distribution, although other stresses were also plotted. Comparison of the modeled and observed polariscope images enabled refinement of the photoelastic constant by minimizing the error between the calculated and measured fields. These results enable quantification of the stress within the polariscope images, determination of material properties, and the modes and mechanisms of stress production within a kidney stone. Such a model may help in interpreting elastic waves in structures, such as stones, toward improving lithotripsy procedures.
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http://dx.doi.org/10.1121/10.0001386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292679PMC
June 2020

An investigation of elastic waves producing stone fracture in burst wave lithotripsy.

J Acoust Soc Am 2020 03;147(3):1607

Department of Acoustics, Physics Faculty, Lomonosov Moscow State University, Leninskie Gory, Moscow 119992, Russia.

Burst wave lithotripsy is a method to noninvasively fragment urinary stones by short pulses of focused ultrasound. In this study, physical mechanisms of stone fracture during burst wave lithotripsy were investigated. Photoelasticity imaging was used to visualize elastic wave propagation in model stones and compare results to numerical calculations. Epoxy and glass stone models were made into rectangular, cylindrical, or irregular geometries and exposed in a degassed water bath to focused ultrasound bursts at different frequencies. A high-speed camera was used to record images of the stone during exposure through a circular polariscope backlit by a monochromatic flash source. Imaging showed the development of periodic stresses in the stone body with a pattern dependent on frequency. These patterns were identified as guided wave modes in cylinders and plates, which formed standing waves upon reflection from the distal surfaces of the stone model, producing specific locations of stress concentration in the models. Measured phase velocities compared favorably to numerically calculated modes dependent on frequency and material. Artificial stones exposed to bursts produced cracks at positions anticipated by this mechanism. These results support guided wave generation and reflection as a mechanism of stone fracture in burst wave lithotripsy.
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http://dx.doi.org/10.1121/10.0000847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069764PMC
March 2020

QUANTIFICATION OF ACOUSTIC RADIATION FORCES ON SOLID OBJECTS IN FLUID.

Phys Rev Appl 2019 Oct 31;12(4). Epub 2019 Oct 31.

Applied Physics Laboratory, Center for Industrial and Medical Ultrasound, University of Washington, Seattle, WA 98105, USA.

Theoretical models allow design of acoustic traps to manipulate objects with radiation force. Here, a model of the acoustic radiation force by an arbitrary beam on a solid object was validated against measurement. The lateral force in water of different acoustic beams was measured and calculated for spheres of different diameter (2-6 wavelengths in water) and composition. This is the first effort to validate a general model, to quantify the lateral force on a range of objects, and to electronically steer large or dense objects with a single-sided transducer. Vortex beams and two other beam shapes having a ring-shaped pressure field in the focal plane were synthesized in water by a 1.5-MHz, 256-element focused array. Spherical targets (glass, brass, ceramic, 2-6 mm dia.) were placed on an acoustically transparent plastic plate that was normal to the acoustic beam axis and rigidly attached to the array. Each sphere was trapped in the beam as the array with the attached plate was rotated until the bead fell from the acoustic trap because of gravity. Calculated and measured maximum obtained angles agreed on average to within 22%. The maximum lateral force occurred when the target diameter equaled the beam width; however, objects up to 40% larger than the beam width were trapped. The lateral force was comparable to the gravitation force on spheres up to 90 mg (0.0009 N) at beam powers on the order of 10 W. As a step toward manipulating objects, the beams were used to trap and electronically steer the spheres along a two-dimensional path.
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http://dx.doi.org/10.1103/physrevapplied.12.044076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050195PMC
October 2019

Simulation of nonlinear trans-skull focusing and formation of shocks in brain using a fully populated ultrasound array with aberration correction.

J Acoust Soc Am 2019 09;146(3):1786

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia.

Multi-element high-intensity focused ultrasound phased arrays in the shape of hemispheres are currently used in clinics for thermal lesioning in deep brain structures. Certain side effects of overheating non-targeted tissues and skull bones have been revealed. Here, an approach is developed to mitigate these effects. A specific design of a fully populated 256-element 1-MHz array shaped as a spherical segment (F-number, F = 1) and filled by randomly distributed equal-area polygonal elements is proposed. Capability of the array to generate high-amplitude shock fronts at the focus is tested in simulations by combining three numerical algorithms for linear and nonlinear field modeling and aberration correction. The algorithms are based on the combination of the Rayleigh integral, a linear pseudo-spectral time domain Kelvin-Voigt model, and nonlinear Westervelt model to account for the effects of inhomogeneities, aberrations, reflections, absorption, nonlinearity, and shear waves in the skull. It is shown that the proposed array can generate nonlinear waveforms with shock amplitudes >60 MPa at the focus deep inside the brain without exceeding the existing technical limitation on the intensity of 40 W/cm at the array elements. Such shock amplitudes are sufficient for mechanical ablation of brain tissues using the boiling histotripsy approach and implementation of other shock-based therapies.
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http://dx.doi.org/10.1121/1.5126685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064313PMC
September 2019

Ultrasound-based cell sorting with microbubbles: A feasibility study.

J Acoust Soc Am 2018 07;144(1):41

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington 98105, USA.

The isolation and sorting of cells is an important process in research and hospital labs. Most large research and commercial labs incorporate fluorescently or magnetically labeled antibodies adherent to cell surface antigens for cell identification and separation. In this paper, a process is described that merges biochemical labeling with ultrasound-based separation. Instead of lasers and fluorophore tags, or magnets and magnetic particle tags, the technique uses ultrasound and microbubble tags. Streptavidin-labeled microbubbles were mixed with a human acute lymphoblastic leukemia cell line, CCL 119, conjugated with biotinylated anti-CD7 antibodies. Tagged cells were forced under ultrasound, and their displacement and velocity quantified. Differential displacement in a flow stream was quantified against erythrocytes, which showed almost no displacement under ultrasound. A model for the acoustic radiation force on the conjugated pairs compares favorably with observations. This technology may improve on current time-consuming and costly purification procedures.
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http://dx.doi.org/10.1121/1.5044405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029934PMC
July 2018

Field Characterization and Compensation of Vibrational Nonuniformity for a 256-Element Focused Ultrasound Phased Array.

IEEE Trans Ultrason Ferroelectr Freq Control 2018 09 27;65(9):1618-1630. Epub 2018 Jun 27.

Multielement focused ultrasound phased arrays have been used in therapeutic applications to treat large tissue volumes by electronic steering of the focus, to target multiple simultaneous foci, and to correct aberration caused by inhomogeneous tissue pathways. There is an increasing interest in using arrays to generate more complex beam shapes and corresponding acoustic radiation force patterns for manipulation of particles such as kidney stones. Toward this end, experimental and computational tools are needed to enable accurate delivery of desired transducer vibrations and corresponding ultrasound fields. The purpose of this paper was to characterize the vibrations of a 256-element array at 1.5 MHz, implement strategies to compensate for variability, and test the ability to generate specified vortex beams that are relevant to particle manipulation. The characterization of the array output was performed in water using both element-by-element measurements at the focus of the array and holography measurements for which all the elements were excited simultaneously. Both methods were used to quantify each element's output so that the power of each element could be equalized. Vortex beams generated using both compensation strategies were measured and compared to the Rayleigh integral simulations of fields generated by an idealized array based on the manufacturer's specifications. Although both approaches improved beam axisymmetry, compensation based on holography measurements had half the error relative to the simulation results in comparison to the element-by-element method.
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http://dx.doi.org/10.1109/TUFFC.2018.2851188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344030PMC
September 2018

Method for Designing Multielement Fully Populated Random Phased Arrays for Ultrasound Surgery Applications.

IEEE Trans Ultrason Ferroelectr Freq Control 2018 04;65(4):630-637

Maximizing the power of multielement phased arrays is a critical factor for high-intensity focused ultrasound (HIFU) applications such as histotripsy and transcostal sonications. This can be achieved by a tight packing of the array elements. Good electronic focusing capabilities are also required. Currently used quasi-random arrays with a relatively low filling factor of about 60% have this focusing ability. Here, a novel method of designing random HIFU arrays with the maximum possible filling factor (100% if no gaps between elements needed in practice are introduced) and polygonal elements of equal area and slightly different shapes based on the capacity-constrained tessellation is described. The method is validated by comparing designs of two arrays with the same geometric and physical parameters: an existing 256-element array with a compact 16-spirals layout of circular elements and the proposed array with the maximum possible filling factor. Introduction of a 0.5-mm gap between the elements of the new array resulted in a reduction of its filling factor to 86%, as compared with 61% for the spiral array. It is shown that for the same intensity at the elements, the proposed array provides two times higher total power while maintaining the same electronic focusing capabilities as compared to the spiral one. Furthermore, the surface of the capacity-constrained tessellation array, its boundary, and a central opening can have arbitrary shapes.
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http://dx.doi.org/10.1109/TUFFC.2018.2800160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903437PMC
April 2018

The role of trapped bubbles in kidney stone detection with the color Doppler ultrasound twinkling artifact.

Phys Med Biol 2018 01 9;63(2):025011. Epub 2018 Jan 9.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th St., Seattle, WA 98105, United States of America. Department of Mechanical Engineering, University of Washington, Stevens Way, Box 352600, Seattle, WA 98195, United States of America. Current address: Graduate Program in Acoustics, The Pennsylvania State University, 201E Applied Science Building, University Park, PA 16802, United States of America. Author to whom any correspondence should be addressed.

The color Doppler ultrasound twinkling artifact, which highlights kidney stones with rapidly changing color, has the potential to improve stone detection; however, its inconsistent appearance has limited its clinical utility. Recently, it was proposed stable crevice bubbles on the kidney stone surface cause twinkling; however, the hypothesis is not fully accepted because the bubbles have not been directly observed. In this paper, the micron or submicron-sized bubbles predicted by the crevice bubble hypothesis are enlarged in kidney stones of five primary compositions by exposure to acoustic rarefaction pulses or hypobaric static pressures in order to simultaneously capture their appearance by high-speed photography and ultrasound imaging. On filming stones that twinkle, consecutive rarefaction pulses from a lithotripter caused some bubbles to reproducibly grow from specific locations on the stone surface, suggesting the presence of pre-existing crevice bubbles. Hyperbaric and hypobaric static pressures were found to modify the twinkling artifact; however, the simple expectation that hyperbaric exposures reduce and hypobaric pressures increase twinkling by shrinking and enlarging bubbles, respectively, largely held for rough-surfaced stones but was inadequate for smoother stones. Twinkling was found to increase or decrease in response to elevated static pressure on smooth stones, perhaps because of the compression of internal voids. These results support the crevice bubble hypothesis of twinkling and suggest the kidney stone crevices that give rise to the twinkling phenomenon may be internal as well as external.
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http://dx.doi.org/10.1088/1361-6560/aa9a2fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791757PMC
January 2018

Modeling of the acoustic radiation force in elastography.

J Acoust Soc Am 2017 08;142(2):947

Physics Faculty, M. V. Lomonosov Moscow State University, 1-2 Leninskiye Gory, Moscow GSP-1, Russia.

Elastography is a non-invasive imaging technique that can assess in vivo tissue stiffness. In shear wave elastography imaging, the acoustic radiation force (ARF) produced by focused ultrasound generates a local force that produces shear waves. The authors compare three existing formulations for the ARF: its full expression in the second-order approximation and two simplified formulations using a quasi-plane wave and an attenuated plane wave approximation. Analytical expressions for the ARF are derived for the special cases of a concave spherical source and a quasi-Gaussian beam. They provide expressions for the resulting ARF and show discrepancies between the different formulations. For strongly divergent or highly focused beams the ARF expressed by the second-order approximation significantly differs from both simplified formulations. However, despite those differences the second-order and quasi-plane wave approximations create identical shear displacements in tissue. To compute the ARF and the displacements produced by a conventional ultrasound probe, the three formulations were incorporated into the k-Wave simulation package. The second-order and quasi-plane wave approximations give different forces but nearly identical displacements while the plane wave approximation significantly differs. It is concluded that to properly take into account the ultrasound field structure, the second-order or quasi-plane wave approximations should be preferably used.
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http://dx.doi.org/10.1121/1.4998585DOI Listing
August 2017

A Prototype Therapy System for Transcutaneous Application of Boiling Histotripsy.

IEEE Trans Ultrason Ferroelectr Freq Control 2017 10 14;64(10):1542-1557. Epub 2017 Aug 14.

Boiling histotripsy (BH) is a method of focused ultrasound surgery that noninvasively applies millisecond-length pulses with high-amplitude shock fronts to generate liquefied lesions in tissue. Such a technique requires unique outputs compared to a focused ultrasound thermal therapy apparatus, particularly to achieve high in situ pressure levels through intervening tissue. This paper describes the design and characterization of a system capable of producing the necessary pressure to transcutaneously administer BH therapy through clinically relevant overlying tissue paths using pulses with duration up to 10 ms. A high-voltage electronic pulser was constructed to drive a 1-MHz focused ultrasound transducer to produce shock waves with amplitude capable of generating boiling within the pulse duration in tissue. The system output was characterized by numerical modeling with the 3-D Westervelt equation using boundary conditions established by acoustic holography measurements of the source field. Such simulations were found to be in agreement with directly measured focal waveforms. An existing derating method for nonlinear therapeutic fields was used to estimate in situ pressure levels at different tissue depths. The system was tested in ex vivo bovine liver samples to create BH lesions at depths up to 7 cm. Lesions were also created through excised porcine body wall (skin, adipose, and muscle) with 3-5 cm thickness. These results indicate that the system is capable of producing the necessary output for transcutaneous ablation with BH.
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http://dx.doi.org/10.1109/TUFFC.2017.2739649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871228PMC
October 2017

Shock formation and nonlinear saturation effects in the ultrasound field of a diagnostic curvilinear probe.

J Acoust Soc Am 2017 04;141(4):2327

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th Street, Seattle, Washington 98105, USA.

Newer imaging and therapeutic ultrasound technologies may benefit from in situ pressure levels higher than conventional diagnostic ultrasound. One example is the recently developed use of ultrasonic radiation force to move kidney stones and residual fragments out of the urinary collecting system. A commercial diagnostic 2.3 MHz C5-2 array probe has been used to deliver the acoustic pushing pulses. The probe is a curvilinear array comprising 128 elements equally spaced along a convex cylindrical surface. The effectiveness of the treatment can be increased by using higher transducer output to provide a stronger pushing force; however nonlinear acoustic saturation can be a limiting factor. In this work nonlinear propagation effects were analyzed for the C5-2 transducer using a combined measurement and modeling approach. Simulations were based on the three-dimensional Westervelt equation with the boundary condition set to match low power measurements of the acoustic pressure field. Nonlinear focal waveforms simulated for different numbers of operating elements of the array at several output power levels were compared to fiber-optic hydrophone measurements and were found to be in good agreement. It was shown that saturation effects do limit the acoustic pressure in the focal region of a diagnostic imaging probe.
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http://dx.doi.org/10.1121/1.4979261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910004PMC
April 2017

Design of HIFU Transducers for Generating Specified Nonlinear Ultrasound Fields.

IEEE Trans Ultrason Ferroelectr Freq Control 2017 02 20;64(2):374-390. Epub 2016 Oct 20.

Various clinical applications of high-intensity focused ultrasound have different requirements for the pressure levels and degree of nonlinear waveform distortion at the focus. The goal of this paper is to determine transducer design parameters that produce either a specified shock amplitude in the focal waveform or specified peak pressures while still maintaining quasi-linear conditions at the focus. Multiparametric nonlinear modeling based on the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation with an equivalent source boundary condition was employed. Peak pressures, shock amplitudes at the focus, and corresponding source outputs were determined for different transducer geometries and levels of nonlinear distortion. The results are presented in terms of the parameters of an equivalent single-element spherically shaped transducer. The accuracy of the method and its applicability to cases of strongly focused transducers were validated by comparing the KZK modeling data with measurements and nonlinear full diffraction simulations for a single-element source and arrays with 7 and 256 elements. The results provide look-up data for evaluating nonlinear distortions at the focus of existing therapeutic systems as well as for guiding the design of new transducers that generate specified nonlinear fields.
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http://dx.doi.org/10.1109/TUFFC.2016.2619913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300962PMC
February 2017

Experimental Study of Acoustic Radiation Force of an Ultrasound Beam on Absorbing and Scattering Objects.

AIP Conf Proc 2015 Jun;1685

Department of Acoustics, Physics Faculty, Moscow State University, Leninskie Gory, Moscow 119991, Russia; Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40th St. Seattle WA 98105.

Acoustic radiation force is a nonlinear acoustic effect caused by the transfer of wave momentum to absorbing or scattering objects. This phenomenon is exploited in modern ultrasound metrology for measurement of the acoustic power radiated by a source and is used for both therapeutic and diagnostic sources in medical applications. To calculate radiation force an acoustic hologram can be used in conjunction with analytical expressions based on the angular spectrum of the measured field. The results of an experimental investigation of radiation forces in two different cases are presented in this paper. In one case, the radiation force of an obliquely incident ultrasound beam on a large absorber (which completely absorbs the beam) is considered. The second case concerns measurement of the radiation force on a spherical target that is small compared to the beam diameter.
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http://dx.doi.org/10.1063/1.4934404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852870PMC
June 2015

An ultrasonic caliper device for measuring acoustic nonlinearity.

Phys Procedia 2016 ;87:93-98

CIMU, Applied Physics Laboratory, University of Washington, 1013 NE 40 Street, Seattle, WA 98105, USA.

In medical and industrial ultrasound, it is often necessary to measure the acoustic properties of a material. A specific medical application requires measurements of sound speed, attenuation, and nonlinearity to characterize livers being evaluated for transplantation. For this application, a transmission-mode caliper device is proposed in which both transmit and receive transducers are directly coupled to a test sample, the propagation distance is measured with an indicator gage, and receive waveforms are recorded for analysis. In this configuration, accurate measurements of nonlinearity present particular challenges: diffraction effects can be considerable while nonlinear distortions over short distances typically remain small. To enable simple estimates of the nonlinearity coefficient from a quasi-linear approximation to the lossless Burgers' equation, the calipers utilize a large transmitter and plane waves are measured at distances of 15-50 mm. Waves at 667 kHz and pressures between 0.1 and 1 MPa were generated and measured in water at different distances; the nonlinearity coefficient of water was estimated from these measurements with a variability of approximately 10%. Ongoing efforts seek to test caliper performance in other media and improve accuracy via additional transducer calibrations.
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http://dx.doi.org/10.1016/j.phpro.2016.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467533PMC
January 2016

Design of HIFU transducers to generate specific nonlinear ultrasound fields.

Phys Procedia 2016 ;87:132-138

CIMU, Applied Physics Laboratory, University of Washington, Seattle, WA.

Various clinical applications of high intensity focused ultrasound (HIFU) have different requirements on the pressure level and degree of nonlinear waveform distortion at the focus. Applications that utilize nonlinear waves with developed shocks are of growing interest, for example, for mechanical disintegration as well as for accelerated thermal ablation of tissue. In this work, an inverse problem of determining transducer parameters to enable formation of shocks with desired amplitude at the focus is solved. The solution was obtained by performing multiple direct simulations of the parabolic Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation for various parameters of the source. It is shown that results obtained within the parabolic approximation can be used to describe the focal region of single element spherical sources as well as complex transducer arrays. It is also demonstrated that the focal pressure level at which fully developed shocks are formed mainly depends on the focusing angle of the source and only slightly depends on its aperture and operating frequency. Using the simulation results, a 256-element HIFU array operating at 1.5 MHz frequency was designed for a specific application of boiling-histotripsy that relies on the presence of 90-100 MPa shocks at the focus. The size of the array elements and focusing angle of the array were chosen to satisfy technical limitations on the intensity at the array elements and desired shock amplitudes in the focal waveform. Focus steering capabilities of the array were analysed using an open-source T-Array software developed at Moscow State University.
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http://dx.doi.org/10.1016/j.phpro.2016.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451200PMC
January 2016

Acoustic holography as a metrological tool for characterizing medical ultrasound sources and fields.

J Acoust Soc Am 2015 Sep;138(3):1515-32

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 Northeast 40th Street, Seattle, Washington 98105, USA.

Acoustic holography is a powerful technique for characterizing ultrasound sources and the fields they radiate, with the ability to quantify source vibrations and reduce the number of required measurements. These capabilities are increasingly appealing for meeting measurement standards in medical ultrasound; however, associated uncertainties have not been investigated systematically. Here errors associated with holographic representations of a linear, continuous-wave ultrasound field are studied. To facilitate the analysis, error metrics are defined explicitly, and a detailed description of a holography formulation based on the Rayleigh integral is provided. Errors are evaluated both for simulations of a typical therapeutic ultrasound source and for physical experiments with three different ultrasound sources. Simulated experiments explore sampling errors introduced by the use of a finite number of measurements, geometric uncertainties in the actual positions of acquired measurements, and uncertainties in the properties of the propagation medium. Results demonstrate the theoretical feasibility of keeping errors less than about 1%. Typical errors in physical experiments were somewhat larger, on the order of a few percent; comparison with simulations provides specific guidelines for improving the experimental implementation to reduce these errors. Overall, results suggest that holography can be implemented successfully as a metrological tool with small, quantifiable errors.
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http://dx.doi.org/10.1121/1.4928396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575327PMC
September 2015

Ultrasonic atomization of liquids in drop-chain acoustic fountains.

J Fluid Mech 2015 Mar;766:129-146

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, WA 98105, USA.

When focused ultrasound waves of moderate intensity in liquid encounter an air interface, a chain of drops emerges from the liquid surface to form what is known as a drop-chain fountain. Atomization, or the emission of micro-droplets, occurs when the acoustic intensity exceeds a liquid-dependent threshold. While the cavitation-wave hypothesis, which states that atomization arises from a combination of capillary-wave instabilities and cavitation bubble oscillations, is currently the most accepted theory of atomization, more data on the roles of cavitation, capillary waves, and even heat deposition or boiling would be valuable. In this paper, we experimentally test whether bubbles are a significant mechanism of atomization in drop-chain fountains. High-speed photography was used to observe the formation and atomization of drop-chain fountains composed of water and other liquids. For a range of ultrasonic frequencies and liquid sound speeds, it was found that the drop diameters approximately equalled the ultrasonic wavelengths. When water was exchanged for other liquids, it was observed that the atomization threshold increased with shear viscosity. Upon heating water, it was found that the time to commence atomization decreased with increasing temperature. Finally, water was atomized in an overpressure chamber where it was found that atomization was significantly diminished when the static pressure was increased. These results indicate that bubbles, generated by either acoustic cavitation or boiling, contribute significantly to atomization in the drop-chain fountain.
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http://dx.doi.org/10.1017/jfm.2015.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428615PMC
March 2015

Investigation into the mechanisms of tissue atomization by high-intensity focused ultrasound.

Ultrasound Med Biol 2015 May 3;41(5):1372-85. Epub 2015 Feb 3.

Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, Seattle, Washington, USA.

Ultrasonic atomization, or the emission of a fog of droplets, was recently proposed to explain tissue fractionation in boiling histotripsy. However, even though liquid atomization has been studied extensively, the mechanisms underlying tissue atomization remain unclear. In the work described here, high-speed photography and overpressure were used to evaluate the role of bubbles in tissue atomization. As static pressure increased, the degree of fractionation decreased, and the ex vivo tissue became thermally denatured. The effect of surface wetness on atomization was also evaluated in vivo and in tissue-mimicking gels, where surface wetness was found to enhance atomization by forming surface instabilities that augment cavitation. In addition, experimental results indicated that wetting collagenous tissues, such as the liver capsule, allowed atomization to breach such barriers. These results highlight the importance of bubbles and surface instabilities in atomization and could be used to enhance boiling histotripsy for transition to clinical use.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2014.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398613PMC
May 2015

A new active cavitation mapping technique for pulsed HIFU applications--bubble Doppler.

IEEE Trans Ultrason Ferroelectr Freq Control 2014 Oct;61(10):1698-708

In this work, a new active cavitation mapping technique for pulsed high-intensity focused ultrasound (pHIFU) applications termed bubble Doppler is proposed and its feasibility is tested in tissue-mimicking gel phantoms. pHIFU therapy uses short pulses, delivered at low pulse repetition frequency, to cause transient bubble activity that has been shown to enhance drug and gene delivery to tissues. The current gold standard for detecting and monitoring cavitation activity during pHIFU treatments is passive cavitation detection (PCD), which provides minimal information on the spatial distribution of the bubbles. B-mode imaging can detect hyperecho formation, but has very limited sensitivity, especially to small, transient microbubbles. The bubble Doppler method proposed here is based on a fusion of the adaptations of three Doppler techniques that had been previously developed for imaging of ultrasound contrast agents-color Doppler, pulse-inversion Doppler, and decorrelation Doppler. Doppler ensemble pulses were interleaved with therapeutic pHIFU pulses using three different pulse sequences and standard Doppler processing was applied to the received echoes. The information yielded by each of the techniques on the distribution and characteristics of pHIFU-induced cavitation bubbles was evaluated separately, and found to be complementary. The unified approach-bubble Doppler-was then proposed to both spatially map the presence of transient bubbles and to estimate their sizes and the degree of nonlinearity.
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http://dx.doi.org/10.1109/TUFFC.2014.006502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454370PMC
October 2014

Fragmentation of urinary calculi in vitro by burst wave lithotripsy.

J Urol 2015 Jan 9;193(1):338-44. Epub 2014 Aug 9.

Department of Urology, School of Medicine, University of Washington, Seattle, Washington; Division of Urology, Department of Veteran Affairs Medical Center, Seattle, Washington.

Purpose: We developed a new method of lithotripsy that uses short, broadly focused bursts of ultrasound rather than shock waves to fragment stones. We investigated the characteristics of stone comminution by burst wave lithotripsy in vitro.

Materials And Methods: Artificial and natural stones (mean ± SD size 8.2 ± 3.0 mm, range 5 to 15) were treated with ultrasound bursts using a focused transducer in a water bath. Stones were exposed to bursts with focal pressure amplitude of 6.5 MPa or less at a 200 Hz burst repetition rate until completely fragmented. Ultrasound frequencies of 170, 285 and 800 kHz were applied using 3 transducers, respectively. Time to fragmentation for each stone type was recorded and fragment size distribution was measured by sieving.

Results: Stones exposed to ultrasound bursts were fragmented at focal pressure amplitudes of 2.8 MPa or greater at 170 kHz. Fractures appeared along the stone surface, resulting in fragments that separated at the surface nearest to the transducer until the stone was disintegrated. All natural and artificial stones were fragmented at the highest focal pressure of 6.5 MPa with a mean treatment duration of 36 seconds for uric acid stones to 14.7 minutes for cystine stones. At a frequency of 170 kHz the largest artificial stone fragments were less than 4 mm. Exposure at 285 and 800 kHz produced only fragments less than 2 mm and less than 1 mm, respectively.

Conclusions: Stone comminution with burst wave lithotripsy is feasible as a potential noninvasive treatment method for nephrolithiasis. Adjusting the fundamental ultrasound frequency allows for stone fragment size to be controlled.
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http://dx.doi.org/10.1016/j.juro.2014.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384893PMC
January 2015
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