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Adam Maxwell Research Assistant Professor, Urology maxwell@apl.washington.edu Phone 206-221-6530 |
Videos
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Ultrasonic tweezers: Technology to lift and steer solid objects in a living body In a recent paper, a CIMU team describes successful experiments to manipulate a solid object within a living body with ultrasound beams transmitted through the skin. |
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15 Jul 2020
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A collaborative, international research teams developed and tuned an ultrasound transducer to create vortex shaped beams that can trap, grab, levitate, and move in three dimensions mm-scale objects. The team is working to apply this technology to their all-in-one kidney stone treatment system that, in clinical trials, uses ultrasound to non-invasively break, erode, and move stones and stone fragments out of the kidney so that they may pass naturally from the body. |
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Mechanical Tissue Ablation with Focused Ultrasound An experimental noninvasive surgery method uses nonlinear ultrasound pulses to liquefy tissue at remote target sites within a small focal region without damaging intervening tissues. A multi-institution, international team led by CIMU researchers is applying the method to the focal treatment of prostate tumors. |
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19 Mar 2020
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Boiling histotripsy utilizes sequences of millisecond-duration HIFU pulses with high-amplitude shocks that form at the focus by nonlinear propagation effects. Due to strong attenuation of the ultrasound energy at the shocks, these nonlinear waves rapidly heat tissue and generate millimeter-sized boiling bubbles at the focus within each pulse. Then the further interaction of subsequent shocks with the vapor cavity causes tissue disintegration into subcellular debris through the acoustic atomization mechanism. |
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PIXUL: PIXelated ULtrasound Speeds Disease Biomarker Search |
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26 Apr 2018
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Accurate assessment of chromatin modifications can be used to improve detection and treatment of various diseases. Further, accurate assessment of chromatin modifications can have an important role in designing new drug therapies. This novel technology applies miniature ultrasound transducers to shear chromatin in standard 96-well microplates. PIXUL saves researchers hours of sample preparation time and reduces sample degradation. |
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Burst Wave Lithotripsy: An Experimental Method to Fragment Kidney Stones CIMU researchers are investigating a noninvasive method to fragment kidney stones using ultrasound pulses rather than shock waves. Consecutive acoustic cycles accumulate and concentrate energy within the stone. The technique can be 'tuned' to create small fragments, potentially improving the success rate of lithotripsy procedures. |
20 Nov 2014
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Publications |
2000-present and while at APL-UW |
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Treating porcine abscesses with histotripsy: A pilot study Matula, T.J., Y.-N. Wang, T. Khokhlova, D.F. Leotta, J. Kucewicz, A.A. Brayman, M. Bruce, A.D. Maxwell, B.E. MacConaghy, G. Thomas, V.P. Chernikov, S.V. Buravkov, V.A. Khokhlova, K. Richmond, K. Chan, W. Monsky, "Treating porcine abscesses with histotripsy: A pilot study," Ultrasound Med. Biol., 47, 603-619, doi:10.1016/j.ultrasmedbio.2020.10.011, 2021. |
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1 Mar 2021 ![]() |
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Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical washout when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses. |
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First in-human burst wave lithotripsy for kidney stone comminution: Initial two case studies Harper, J.D., I. Metzler, M.K. Hall, T.T. Chen, A.D. Maxwell, B.W. Cunitz, B. Dunmire, J. Thiel, J.C. Williams, M.R. Bailey, and M.D. Sorensen, "First in-human burst wave lithotripsy for kidney stone comminution: Initial two case studies," J. Endourol., EOR, doi:10.1089/end.2020.0725, 2020. |
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1 Nov 2020 ![]() |
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Purpose: To test the effectiveness (Participant A) and tolerability (Participant B) of urinary stone comminution in the first in-human trial of a new technology, burst wave lithotripsy (BWL). |
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In vitro evaluation of urinary stone comminution with a clinical burst wave lithotripsy system Ramesh, S., T.T. Chen, A.D. Maxwell, B.W. Cunitz, B. Dunmire, J. Thiel, J.C. Williams, A. Gardner, Z. Liu, I. Metzler, J.D. Harper, M.D. Sorensen, and M.R. Bailey, "In vitro evaluation of urinary stone comminution with a clinical burst wave lithotripsy system," J. Endourol., 34, 1167-1173, doi:10.1089/end.2019.0873, 2020. |
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1 Nov 2020 ![]() |
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Objective: Our goals were to validate stone comminution with an investigational burst wave lithotripsy (BWL) system in patient-relevant conditions and to evaluate the use of ultrasonic propulsion to move a stone or fragments to aid in observing the treatment endpoint. |
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A simulated model for fluid and tissue heating during pediatric laser lithotripsy Ellison, J.S., B. MacConaghy, T.L. Hall, W.W. Roberts, A.D. Maxwell, "A simulated model for fluid and tissue heating during pediatric laser lithotripsy," J. Pediatr. Urol., 16, doi:10.1016/j.jpurol.2020.07.014, 2020. |
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1 Oct 2020 ![]() |
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Laser lithotripsy (LL) is a common modality for treatment of children and adolescents with nephrolithiasis. Recent introduction of higher-powered lasers may result in more efficacious "dusting" of urinary calculi. However, in vivo animal studies and computational simulations have demonstrated rapid and sustained rise of fluid temperatures with LL, possibly resulting in irreversible tissue damage. How fluid and tissue heating during LL vary with pediatric urinary tract development, however, is unknown. We hypothesize that kidneys of younger children will be more susceptible to changes in fluid temperature and therefore tissue damage than those of older children. Smaller renal size is more susceptible to thermal changes induced by LL. However, power settings equal to or greater than 20 W can result in temperatures high enough for tissue damage at any age. Continuous pressure flow and intermittent laser activity may mitigate the potential thermal damage from high power LL. |
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Histotripsy treatment of abscesses Matula, T.J., Y.-N. Wang, T. Khokhlova, D.F. Leotta, J. Kucewicz, A.A. Brayman, M. Bruce, A.D. Maxwell, B.E. MacConaghy, G. Thomas, K. Richmond, K. Chan, and W. Monsky, "Histotripsy treatment of abscesses," in Proc., IEEE International Ultrasonics Symposium, 7-11 September, Las Vegas, NV, doi:10.1109/IUS46767.2020.9251683 (IEEE, 2020). |
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7 Sep 2020 ![]() |
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Abscesses are walled-off collections of infected fluids containing pus and bacteria. They are often treated with percutaneous drainage in which a drainage catheter may be sutured in place for up to several weeks. Complications such as clogged drains or secondary infections require rehospitalization and wound management. Bacteria are susceptible to mechanical damage, and thus we hypothesize that histotripsy may be a potential new paradigm for treating abscesses noninvasively, without the need for long term catheterization and antibiotics. We developed a porcine animal model that recapitulates some of the features of human abscesses (including size and loculations). Boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses in this porcine model. Ultrasound imaging was used to evaluate abscess maturity, for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses. |
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Ultrasound imaging of abscesses before and during histotripsy treatment Bruce, M., D.F. Leotta, Y.-N. Wang, T. Khokhlova, J. Kucewicz, A.D. Maxwell, K. Chan, W. Monsky, and T.J. Matula, "Ultrasound imaging of abscesses before and during histotripsy treatment," in Proc., IEEE International Ultrasonics Symposium, 7-11 September, Las Vegas, NV, doi:10.1109/IUS46767.2020.9251386 (IEEE, 2020). |
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7 Sep 2020 ![]() |
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Abscesses are walled-off collections of infected fluids most often treated with percutaneous drains placed under CT guidance. Complications such as clogged drains or secondary infections require rehospitalization and wound management. Histotripsy treatment has the potential to eliminate the need for long term catheterization and antibiotics. The progression of abscess development has yet to be fully described. The objective of this study was to use the latest advances in non-contrast ultrasound technologies to characterize abscess development in a porcine animal model. Intramuscular or subcutaneous injections of bacteria plus dextran particles as an irritant led to identifiable abscesses over a 2- to 3-week period. Ultrasound imaging was performed at least weekly, in some cases with a 3D tracking device that provided quantifiable size and shape measurements. Abscess progression was also measured with a plane-wave Doppler mode providing increased sensitivity to low-velocity flows, while abscess stiffness was quantified using shear wave elastography. Most of the mature abscesses were characterized by a rounded core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. A treatable abscess was defined by its hypervascular rim and avascular core. Stiffness varied within the abscess but generally decreased over time. Abscess echogenicity, shape, stiffness and vascularity potentially provide features to identify lesions suitable for treatment. |
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Noninvasive acoustic manipulation of objects in a living body Ghanem, M.A., A.D. Maxwell, Y.-N. Wang, B.W. Cunitz, V.A. Khokhlova, O.A. Sopozhnikov, and M.R. Bailey, "Noninvasive acoustic manipulation of objects in a living body," Proc. Nat. Acad. Sci. USA, 117, 16,848-16,855, doi:10.1073/pnas.2001779117, 2020. |
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21 Jul 2020 ![]() |
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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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Design, fabrication, and characterization of broad beam transducers for fragmenting large renal calculi with burst wave lithotripsy Randad, A., M.A. Ghanem, M.R. Bailey, A.D. Maxwell, "Design, fabrication, and characterization of broad beam transducers for fragmenting large renal calculi with burst wave lithotripsy, " J. Acoust. Soc. Am., 148, 44-50, doi:10.1121/10.0001512, 2020. |
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1 Jul 2020 ![]() |
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Burst wave lithotripsy (BWL) is a technology for comminuting urinary stones. A BWL transducer's requirements of high-pressure output, limited acoustic window, specific focal depth, and frequency to produce fragments of passable size constrain focal beamwidth. However, BWL is most effective with a beam wider than the stone. To produce a broad-beam, an iterative angular spectrum approach was used to calculate a phase screen that was realized with a rapid prototyped lens. The technique did not accurately replicate a target beam profile when an axisymmetric profile was chosen. Adding asymmetric weighting functions to the target profile achieved appropriate beamwidth. Lenses were designed to create a spherically focused narrow-beam (6 mm) and a broad-beam (11 mm) with a 350-kHz transducer and 84-mm focal depth. Both lenses were used to fragment artificial stones (11 mm long) in a water bath, and fragmentation rates were compared. The linearly simulated and measured broad beamwidths that were 12 mm and 11 mm, respectively, with a 2-mm-wide null at center. The broad-beam and the narrow-beam lenses fragmented 44 ± 9% and 16 ± 4% (p = 0.007, N = 3) of a stone by weight, respectively, in the same duration at the same peak negative pressure. The method broadened the focus and improved the BWL rate of fragmentation of large stones. |
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Modeling of photoelastic imaging of mechanical stresses in transparent solids mimicking kidney stones Sapozhnikov, O.A., A.D. Maxwell, and M.R. Bailey, "Modeling of photoelastic imaging of mechanical stresses in transparent solids mimicking kidney stones," J. Acoust. Soc. Am., 147, 3819-3829, doi:10.1121/10.0001386, 2020. |
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1 Jun 2020 ![]() |
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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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An investigation of elastic waves producing stone fracture in burst wave lithotripsy Maxwell, A.D., B. MacConaghy, M.R. Bailey, and O.A. Sapozhnikov, "An investigation of elastic waves producing stone fracture in burst wave lithotripsy," J. Acoust. Soc. Am., 147, 1607-1622, doi:10.1121/10.0000847, 2020. |
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1 Mar 2020 ![]() |
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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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Defining thermally safe laser lithotripsy power and irrigation parameters: In vitro model Aldoukhi, A.H., K.M. Black, T.L. Hall, K.R. Ghani, A.D. Maxwell, B. MacConaghy, and W.W. Roberts, "Defining thermally safe laser lithotripsy power and irrigation parameters: In vitro model," J. Endourol., 34, 76-81, doi:10.1089/end.2019.0499, 2020. |
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16 Jan 2020 ![]() |
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High-power laser settings are commonly employed for stone dusting techniques. Previous in vitro and in vivo studies have demonstrated that a toxic thermal dose can result from treatment within a renal calix without adequate irrigation. Hence, both laser power and irrigation rate must be considered together to determine safe laser lithotripsy parameters. The objective of this in vitro study was to map parameter safety boundaries and create guidelines for selection of safe laser and irrigation settings. |
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Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney Khokhlova, T.D., G.R. Schade, Y.-N. Wang, S.V. Buravkov, V.P. Chernikov, J.C. Simon, F. Starr, A.D. Maxwell, M.R. Bailey, W. Kreider, and V.A. Khokhlova, "Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney," Sci. Rep., 9, 20176, doi:10.1038/s41598-019-56658-7, 2019. |
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27 Dec 2019 ![]() |
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Boiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 530 pulses of 110 ms duration per focus, 1% duty cycle, peak acoustic powers 0.93.8 kW, sonication foci spaced 11.5 mm apart in a rectangular grid with 515 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver. |
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Evaluation of renal stone comminution and injury by burst wave lithotripsy in a pig model Maxwell, A.D., Y.-N. Wang, W. Kreider, B.W. Cunitz, F. Starr, D. Lee, Y. Nazari, J.C. Williams Jr., M.R. Bailey, and M.D. Sorensen, "Evaluation of renal stone comminution and injury by burst wave lithotripsy in a pig model," J. Endourol., 33, doi:10.1089/end.2018.0886, 2019. |
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15 Oct 2019 ![]() |
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Burst wave lithotripsy is an experimental technology to noninvasively fragment kidney stones with focused bursts of ultrasound (US). This study evaluated the safety and effectiveness of specific lithotripsy parameters in a porcine model of nephrolithiasis. |
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Quantification of acoustic radiation forces on solid objects in fluid Ghanem, M.A., A.D. Maxwell, O.A. Sapozhnikov, V.A. Khokhlova, and M.R. Bailey, "Quantification of acoustic radiation forces on solid objects in fluid," Phys. Rev. Appl., 12, doi:10.1103/PhysRevApplied.12.044076, 2019. |
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1 Oct 2019 ![]() |
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Theoretical models allow design of acoustic traps to manipulate objects with radiation force. A model of the acoustic radiation force by an arbitrary beam on a solid object is validated against measurement. The lateral force in water of different acoustic beams is measured and calculated for spheres of different diameters (26 wavelengths λ in water) and compositions. 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 are synthesized in water by a 1.5-MHz, 256-element focused array. Spherical targets (glass, brass, ceramic, 26 mm dia.) are placed on an acoustically transparent plastic plate that is normal to the acoustic beam axis and rigidly attached to the array. Each sphere is trapped in the beam as the array with the attached plate is rotated until the sphere falls from the acoustic trap because of gravity. Calculated and measured maximum obtained angles agree on average to within 22%. The maximum lateral force occurs when the target diameter equals the beam width; however, objects up to 40% larger than the beam width are trapped. The lateral force is 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 are used to trap and electronically steer the spheres along a two-dimensional path. |
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The impact of dust and confinement on fragmentation of kidney stones by shockwave lithotripsy in tissue phantoms Randad, A., J. Ahn, W. Kreider, M.R. Bailey, J.D. Harper, M.D. Sorensen, and A.D. Maxwell, "The impact of dust and confinement on fragmentation of kidney stones by shockwave lithotripsy in tissue phantoms," J. Endourol., 33, doi:10.1089/end.2018.0516, 2019. |
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1 May 2019 ![]() |
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Objective: The goal was to test whether stone composition and kidney phantom configuration affected comminution in extracorporeal shockwave lithotripsy (SWL) laboratory tests. Confinement may enhance the accumulation of dust and associated cavitation bubbles in the fluid surrounding the stone. It is known that high shockwave delivery rates in SWL are less effective because bubbles generated by one shockwave do not have sufficient time to dissolve, thereby shielding the next shockwave. |
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PIXUL-ChIP: Integrated high-throughput sample preparation and analytical platform for epigenetic studies Bomsztyk, K., D. Mar, Y. Wang, O. Denisenko, C. Ware, C.D. Frazar, A. Blattler, A.D. Maxwell, B.E. MacConaghy, and T.J. Matula, "PIXUL-ChIP: Integrated high-throughput sample preparation and analytical platform for epigenetic studies," Nucleic Acids Res., 47, doi:10.1093/nar/gkz222, 2019. |
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30 Mar 2019 ![]() |
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Chromatin immunoprecipitation (ChIP) is the most widely used approach for identification of genome-associated proteins and their modifications. We have previously introduced a microplate-based ChIP platform, Matrix ChIP, where the entire ChIP procedure is done on the same plate without sample transfers. Compared to conventional ChIP protocols, the Matrix ChIP assay is faster and has increased throughput. However, even with microplate ChIP assays, sample preparation and chromatin fragmentation (which is required to map genomic locations) remains a major bottleneck. We have developed a novel technology (termed 'PIXUL') utilizing an array of ultrasound transducers for simultaneous shearing of samples in standard 96-well microplates. We integrated PIXUL with Matrix ChIP ('PIXUL-ChIP'), that allows for fast, reproducible, low-cost and high-throughput sample preparation and ChIP analysis of 96 samples (cell culture or tissues) in one day. Further, we demonstrated that chromatin prepared using PIXUL can be used in an existing ChIP-seq workflow. Thus, the high-throughput capacity of PIXUL-ChIP provides the means to carry out ChIP-qPCR or ChIP-seq experiments involving dozens of samples. Given the complexity of epigenetic processes, the use of PIXUL-ChIP will advance our understanding of these processes in health and disease, as well as facilitate screening of epigenetic drugs. |
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Simulation of laser lithotripsy-induced heating in the urinary tract Maxwell, A.D., B. MacConaghy, J.D. Harper, A.H. Aldoukhi, T.L. Hall, and W.W. Roberts, "Simulation of laser lithotripsy-induced heating in the urinary tract," J. Endourol., 33, doi:10.1089/end.2018.0485, 2019. |
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15 Feb 2019 ![]() |
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Purpose: Holmium laser lithotripsy is a common modality used to fragment urinary stones during ureteroscopy. Laser energy deposited during activation produces heat and potentially causes thermal bioeffects. We aimed to characterize laser-induced heating through a computational simulation. |
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Impact of stone type on caviation in burst wave lithotripsy Hunter, C., A.D. Maxwell, B. Cunitz, B. Dunmire, M.D. Sorensen, J.C. Williams Jr., A. Randad, M. Bailey, and W. Kreider, "Impact of stone type on caviation in burst wave lithotripsy," Proc. Mtgs. Acoust., 35, 020005, doi:10.1121/2.0000950, 2018. |
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26 Dec 2018 ![]() |
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Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada. |
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Modeling and numerical simulation of the bubble cloud dynamics in an ultrasound field for burst wave lithotripsy Maeda, K., T. Colonius, A. Maxwell, W. Kreider, and M. Bailey, "Modeling and numerical simulation of the bubble cloud dynamics in an ultrasound field for burst wave lithotripsy," Proc. Mtgs. Acoust., 35, 020006, doi:10.1121/2.0000946, 2018. |
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26 Dec 2018 ![]() |
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176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada. |
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Update on clinical trials of kidney stone repositioning and preclinical results of stone breaking with one system Bailey, M.R., Y.-N. Wang, W. Kreider, J.C. Dai, B.W. Cunitz, J.D. Harper, H. Chang, M.D. Sorensen, Z. Liu, O. Levy, B. Dunmire, and A.D. Maxwell, "Update on clinical trials of kidney stone repositioning and preclinical results of stone breaking with one system," Proc. Mtgs. Acoust, 35, 020004, doi:10.1121/2.0000949, 2018. |
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21 Dec 2018 ![]() |
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176th Meeting of the Acoustical Society of America 5-9 November 2018, Victoria, BC, Canada. |
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Mechanical decellularization of tissue volumes using boiling histotripsy Wang, Y.-N., T.D. Khokhlova, S. Buravkov, V. Chernikov, W. Greider, A. Partanen, N. Farr, A. Maxwell, G.R. Schade, and V.A. Khokhlova, "Mechanical decellularization of tissue volumes using boiling histotripsy," Phys. Med. Biol., 6, 235023, doi: |
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4 Dec 2018 ![]() |
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High intensity focused ultrasound (HIFU) is rapidly advancing as an alternative therapy for non-invasively treating specific cancers and other pathological tissues through thermal ablation. A new type of HIFU therapy boiling histotripsy (BH) aims at mechanical fractionation of into subcellular fragments, with a range of accompanying thermal effects that can be tuned from none to substantial depending on the requirements of the application. The degree of mechanical tissue damage induced by BH has been shown to depend on the tissue type, with collagenous structures being most resistant, and cellular structures being most sensitive. This has been reported for single BH lesions, but has not been replicated in large volumes. Such tissue selectivity effect has potential uses involving tissue decellularization for biofabrication technologies as well as mechanical ablation by BH while sparing critical structures. The goal of this study was to investigate tissue decellularization effect in larger, clinically relevant liquefied volumes of tissue, and to evaluate the accumulated thermal effect in the volumetric lesions under different exposure parameters. All BH exposures were performed with a 256-element 1.2-MHz array of a magnetic resonance imaging guided HIFU (MR-HIFU) clinical system (Sonalleve V1, Profound Medical Inc, Mississauga, Canada). The volumetric BH lesions were produced in degassed ex vivo bovine liver using 110-ms long pulses with in situ shock amplitudes of 75100 MPa at the focus and pulse repetition frequencies (PRFs) of 110 Hz covering a range of effects from pure mechanical homogenization to thermal ablation. Multimodal analysis of the lesions was then performed, including microstructure (histological), ultrastructure (electron microscopy), and molecular (biochemistry) methods. Results show a range of tissue effects in terms of the degree of tissue selectivity and the amount of heat generated in large BH lesions, thereby demonstrating potential for treatments tailored to different clinical applications. |
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An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model Wang, Y.-N., W. Kreider, C. Hunter, B.W. Cunitz, J. Thiel, F. Starr, J.C. Dai, Y. Nazari, D. Lee, J.C. Williams, M.R. Bailey, and A.D. Maxwell, "An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model," Proc. Mtgs. Acoust., 35, 02009, doi:10.1121/2.0000975, 2018. |
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5 Nov 2018 ![]() |
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Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada. |
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Design of a transducer for fragmenting large kidney stones using burst wave lithotripsy Randad, A.P., M.A. Ghanem, M.R. Bailey, and A.D. Maxwell, "Design of a transducer for fragmenting large kidney stones using burst wave lithotripsy," Proc. Mtgs. Acoust., 35, 020007, doi:10.1121/2.0000954, 2018. |
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5 Nov 2018 ![]() |
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Proceedings, 176th Meeting of the Acoustical Society of America, 5-9 November 2018, Victoria, BC, Canada. |
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Energy shielding by cavitation bubble clouds in burst wave lithotripsy Maeda, K., A.D. Maxwell, T. Colonius, W. Kreider, and M.R. Bailey, "Energy shielding by cavitation bubble clouds in burst wave lithotripsy," J. Acoust. Soc. Am., 144, 2952-2961, doi:10.1121/1.5079641, 2018 |
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1 Nov 2018 ![]() |
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Combined laboratory experiment and numerical simulation are conducted on bubble clouds nucleated on the surface of a model kidney stone to quantify the energy shielding of the stone caused by cavitation during burst wave lithotripsy (BWL). In the experiment, the bubble clouds are visualized and bubble-scattered acoustics are measured. In the simulation, a compressible, multi-component flow solver is used to capture complex interactions among cavitation bubbles, the stone, and the burst wave. Quantitative agreement is confirmed between results of the experiment and the simulation. In the simulation, a significant shielding of incident wave energy by the bubble clouds is quantified. The magnitude of shielding can reach up to 90% of the energy of the incoming burst wave that otherwise would be transmitted into the stone, suggesting a potential loss of efficacy of stone comminution. There is a strong correlation between the magnitude of the energy shielding and the amplitude of the bubble-scattered acoustics, independent of the initial size and the void fraction of the bubble cloud within a range addressed in the simulation. This correlation could provide for real-time monitoring of cavitation activity in BWL. |
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Dependence of inertial cavitation induced by high intensity focused ultrasound on transducer F-number and nonlinear waveform distortion Khokhlova, T., P. Rosnitskiy, C. Hunter, A. Maxwell, W. Kreider, G. Ter Haar, M. Costa, O. Sapozhnikov, and V. Khokhlova, "Dependence of inertial cavitation induced by high intensity focused ultrasound on transducer F-number and nonlinear waveform distortion," J. Acoust. Soc. Am., 144, 1160, doi:10.1121/1.5052260, 2018. |
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1 Sep 2018 ![]() |
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Pulsed high intensity focused ultrasound was shown to enhance chemotherapeutic drug uptake in tumor tissue through inertial cavitation, which is commonly assumed to require peak rarefactional pressures to exceed a certain threshold. However, recent studies have indicated that inertial cavitation activity also correlates with the presence of shocks at the focus. The shock front amplitude and corresponding peak negative pressure (p) in the focal waveform are primarily determined by the transducer F-number: less focused transducers produce shocks at lower p. Here, the dependence of inertial cavitation activity on the transducer F-number was investigated in agarose gel by monitoring broadband noise emissions with a coaxial passive cavitation detector (PCD) during pulsed exposures (pulse duration 1 ms, pulse repetition frequency 1 Hz) with p varying within 115 MPa. Three 1.5 MHz transducers with the same aperture, but different focal distances (F-numbers 0.77, 1.02, 1.52) were used. PCD signals were processed to extract cavitation probability, persistence, and mean noise level. At the same p, all metrics indicated enhanced cavitation activity at higher F-numbers; specifically, cavitation probability reached 100% when shocks formed at the focus. These results provide further evidence supporting the excitation of inertial cavitation at reduced p by waveforms with nonlinear distortion and shocks. |
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Field characterization and compensation of vibrational nonuniformity for a 256-element focused ultrasound phased array Ghanem, M.A., A.D. Maxwell, W. Kreider, B.W. Cunitz, V.A. Khokhlova, O.A. Sapozhnikov, and M.R. Bailey, "Field characterization and compensation of vibrational nonuniformity for a 256-element focused ultrasound phased array," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 65, 1618-1630, doi:10.1109/TUFFC.2018.2851188, 2018. |
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1 Sep 2018 ![]() |
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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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Caliceal fluid temperature during high-power holmium laser lithotripsy in an in vivo porcine model Aldoukhi, A.H., T.L. Hall, K.R. Ghani, A.D. Maxwell, B. MacConaghy, and W.W. Roberts, "Caliceal fluid temperature during high-power holmium laser lithotripsy in an in vivo porcine model," J. Endourol., 32, 724-729, doi:10.1089/end.2018.0395, 2018. |
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1 Aug 2018 ![]() |
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With increasing use of high-power laser settings for lithotripsy, the potential exists to induce thermal tissue damage. In vitro studies have demonstrated that temperature elevation sufficient to cause thermal tissue damage can occur with certain laser and irrigation settings. The objective of this pilot study was to measure caliceal fluid temperature during high-power laser lithotripsy in an in vivo porcine model. |
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Combined burst wave lithotripsy and ultrasonic propulsion fo improved urinary stone fragmentation Zwaschka, T.A., J.S. Ahn, B.W. Cunitz, M.R. Bailey, B. Dunmire, M.D. Sorensen, J.D. Harper, and A.D. Maxwell, "Combined burst wave lithotripsy and ultrasonic propulsion fo improved urinary stone fragmentation," J. Endourol., 32, 344-349, doi:10.1089/end.2017.0675, 2018. |
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1 Apr 2018 ![]() |
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Design and characterization of a 2-dimensional focused 1.5-MHz ultrasound array with a compact spiral arrangement of 256 circular elements Sapozhnikov, O., M. Ghanem, A. Maxwell, P. Rosnitskiy, P. Yuldashev, W. Kreider, B. Cunitz, M. Bailey, and V. Khokhlova, "Design and characterization of a 2-dimensional focused 1.5-MHz ultrasound array with a compact spiral arrangement of 256 circular elements," Proc., IEEE International Ultrasonics Symposium, 6-9 September, Washington, D.C., doi:10.1109/ULTSYM.2017.8092165 (IEEE, 2017). |
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2 Nov 2017 ![]() |
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Multi-element ultrasound arrays are increasingly used in clinical practice for both imaging and therapy. In therapy, they allow electronic steering, aberration correction, and focusing. To avoid grating lobes, an important requirement for such an array is the absence of periodicity in the arrangement of the elements. A convenient solution is the arrangement of the elements along spirals. The objective of this work was to design, fabricate, and characterize an array for boiling histotripsy applications that is capable of generating shock waves in the focus of up to 100 MPa peak pressure while having a reasonable electronic steering range. |
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Design and characterization of a research phantom for shock-wave enhanced irradiations in high intensity focused ultrasound therapy Kreider, W., B. Dunmire, J. Kucewicz, C. Hunter, T. Khokhlova, G. Schade, A. Maxwell, O. Sapozhnikov, L. Crum, and V. Khokhlova, "Design and characterization of a research phantom for shock-wave enhanced irradiations in high intensity focused ultrasound therapy," Proc., IEEE International Ultrasonics Symposium, 6-9 September, Washington, D.C., doi:10.1109/ULTSYM.2017.8092866 (IEEE, 2017). |
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2 Nov 2017 ![]() |
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The use of shock waves for enhancing thermal effects and mechanically ablating tissue is gaining increased attention in high intensity focused ultrasound (HIFU) applications such as tumor treatment, drug delivery, noninvasive biopsy, and immunotherapy. For abdominal targets, the presence of ribs and inhomogeneous adipose tissue can affect shock formation through aberration, absorption, and diffraction. The goal of this study was to design and validate a phantom for investigating the impact of different tissue structures on shock formation in situ. A transducer with driving electronics was developed to operate at 1.2 MHz with the ability to deliver either short pulses at high powers (up to 5 kW electric power) or continuous output at moderate powers (up to 700 W). Fat and muscle layers were represented by phantoms made from polyvinyl alcohol. Ribs were 3D-printed from a photopolymer material based on 3D CT scan images. Representative targeted tissue was comprised of optically transparent alginate or polyacrylamide gels. The system was characterized by hydrophone measurements free-field in water and in the presence of a body wall or rib phantoms. Shocked waveforms with peak positive/negative pressures of +100 / 20 MPa were measured at the focus in a free field at 1 kW electric source power. When ribs were present, shocks formed at about 50% amplitude at the same power, and higher pressures were measured with ribs positioned closer to the transducer. A uniform body wall structure attenuated shock amplitudes by a smaller amount than non-uniform, and the measurements were insensitive to the axial position of the phantom. Signal magnitude loss at the focus for both the rib phantoms and abdominal wall tissue were consistent with results from real tissues. In addition, boiling histotripsy lesions were generated and visualized in the target gels. The results demonstrate that the presence of ribs and absorptive tissue-mimicking layers do not prevent shock formation at the focus. With real-time lesion visualization, the phantom is suitable for adaptation as a training tool. |
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Stress waves in model kidney stones exposed to burst wave lithotripsy Maxwell, A., B. MacConaghy, M. Bailey, and O. Sapozhnikov, "Stress waves in model kidney stones exposed to burst wave lithotripsy," Proc., IEEE International Ultrasonics Symposium, 6-9 September, Washington, D.C., doi:10.1109/ULTSYM.2017.8092870 (IEEE, 2017). |
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2 Nov 2017 ![]() |
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Burst wave lithotripsy (BWL) is an experimental method to noninvasively fragment urinary calculi using low-frequency focused bursts of ultrasound. To optimize many of the acoustic parameters for this technology, it is necessary to understand the physical interactions between ultrasound bursts and stones. In this study, the interaction of elastic waves with model stones was simulated and experimentally visualized by photoelastography, a technique using polarized light to spatially and temporally visualize stress patterns. |
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A prototype therapy system for transcutaneous application of boiling histotripsy Maxwell, A.D., P.V. Yuldashev, W. Kreider, T.D. Khokhlova, G.R. Schade, T.L. Hall, O.A. Sapozhnikov, M.R. Bailey, and V.A. Khokhlova, "A prototype therapy system for transcutaneous application of boiling histotripsy," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 64, 1542-1557, doi:10.1109/TUFFC.2017.2739649, 2017. |
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1 Oct 2017 ![]() |
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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 35 cm thickness. These results indicate that the system is capable of producing the necessary output for transcutaneous ablation with BH. |
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Ultrasound-induced bubble clusters in tissue-mimicking agar phantoms Movahed, P., W. Kreider, A.D. Maxwell, B. Dunmire, and J.B. Freund, "Ultrasound-induced bubble clusters in tissue-mimicking agar phantoms," Ultrasound Med. Biol., 43, 2318-2328, doi:10.1016/j.ultrasmedbio.2017.06.013, 2017. |
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1 Oct 2017 ![]() |
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Therapeutic ultrasound can drive bubble activity that damages soft tissues. To study the potential mechanisms of such injury, transparent agar tissue-mimicking phantoms were subjected to multiple pressure wave bursts of the kind being considered specifically for burst wave lithotripsy. A high-speed camera recorded bubble activity during each pulse. Various agar concentrations were used to alter the phantom's mechanical properties, especially its stiffness, which was varied by a factor of 3.5. However, the maximum observed bubble radius was insensitive to stiffness. During 1000 wave bursts of a candidate burst wave lithotripsy treatment, bubbles appeared continuously in a region that expanded slowly, primarily toward the transducer. Denser bubble clouds are formed at higher pulse repetition frequency. The specific observations are used to inform the incorporation of damage mechanisms into cavitation models for soft materials. |
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Design of HIFU transducers for generating specified nonlinear ultrasound fields Rosnitskiy, P.B., P.V. Yuldashev, O.A. Sapozhnikov, A.D. Maxwell, W. Greider, M.R. Bailey, and V.A. Khokhlova, "Design of HIFU transducers for generating specified nonlinear ultrasound fields," IEEE Trans. Ultrason., Ferroelect., Freq. Control, 64, 374-390, doi:10.1109/TUFFC.2016.2619913, 2017. |
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1 Feb 2017 ![]() |
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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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Cavitation-induced damage of soft materials by focused ultrasound bursts: A fracture-based bubble dynamics model Movahed, P., W. Kreider, A.D. Maxwell, S.B. Hutchens, and J.B. Freund, "Cavitation-induced damage of soft materials by focused ultrasound bursts: A fracture-based bubble dynamics model," J. Acoust. Soc. Am., 140, 1374-1386, doi:10.1121/1.4961364, 2016. |
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1 Aug 2016 ![]() |
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A generalized RayleighPlesset-type bubble dynamics model with a damage mechanism is developed for cavitation and damage of soft materials by focused ultrasound bursts. This study is linked to recent experimental observations in tissue-mimicking polyacrylamide and agar gel phantoms subjected to bursts of a kind being considered specifically for lithotripsy. These show bubble activation at multiple sites during the initial pulses. More cavities appear continuously through the course of the observations, similar to what is deduced in pig kidney tissues in shock-wave lithotripsy. Two different material models are used to represent the distinct properties of the two gel materials. The polyacrylamide gel is represented with a neo-Hookean elastic model and damaged based upon a maximum-strain criterion; the agar gel is represented with a strain-hardening Fung model and damaged according to the strain-energy-based Griffith's fracture criterion. Estimates based upon independently determined elasticity and viscosity of the two gel materials suggest that bubble confinement should be sufficient to prevent damage in the gels, and presumably injury in some tissues. Damage accumulation is therefore proposed to occur via a material fatigue, which is shown to be consistent with observed delays in widespread cavitation activity. |
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An ultrasonic caliper device for measuring acoustic nonlinearity Hunter, C., O.A Sapozhnikov, A.D. Maxwell, V.A. Khokhlova, Y.-N. Wang, B. MacConaghy, and W. Kreider, "An ultrasonic caliper device for measuring acoustic nonlinearity," Phys. Procedia, 87, 93-98, doi:10.1016/j.phpro.2016.12.015, 2016. |
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1 May 2016 ![]() |
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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 coeffcient from a quasi-linear approximation to the lossless Burgers’ equation, the calipers utilize a large transmitter and plane waves are measured at distances of 1550 mm. Waves at 667 kHz and pressures between 0.1 and 1 MPa were generated and measured in water at different distances; the nonlinearity coeffcient 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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Design of HIFU transducers to generate specific nonlinear ultrasound fields Khokhlova, V.A., P.V. Yuldashev, P.B. Rosnitskiy, A.D. Maxwell, W. Kreider, M.R. Bailey, and O.A. Sapozhnikov, "Design of HIFU transducers to generate specific nonlinear ultrasound fields," Phys. Proced., 87, 132-138, doi:10.1016/j.phpro.2016.12.020, 2016. |
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1 May 2016 ![]() |
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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 KhokhlovZabolotskayaKuznetsov (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 90100 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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Bubble-induced color Doppler feedback for histotripsy tissue fractionation Miller, R.M., X. Zhang, A.D. Maxwell, C.A. Cain, and Z. Xu, "Bubble-induced color Doppler feedback for histotripsy tissue fractionation," IEEE Trans. Ultrasoun. Ferroelect. Freq. Control, 63, 408-419, doi:10.1109/TUFFC.2016.2525859, 2016. |
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1 Mar 2016 ![]() |
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Histotripsy therapy produces cavitating bubble clouds to increasingly fractionate and eventually liquefy tissue using high-intensity ultrasound pulses. Following cavitation generated by each pulse, coherent motion of the cavitation residual nuclei can be detected using metrics formed from ultrasound color Doppler acquisitions. In this paper, three experiments were performed to investigate the characteristics of this motion as real-time feedback on histotripsy tissue fractionation. In the first experiment, bubble-induced color Doppler (BCD) and particle image velocimetry (PIV) analysis monitored the residual cavitation nuclei in the treatment region in an agarose tissue phantom treated with two-cycle histotripsy pulses at >30 MPa using a 500-kHz transducer. Both BCD and PIV results showed brief chaotic motion of the residual nuclei followed by coherent motion first moving away from the transducer and then rebounding back. Velocity measurements from both PIV and BCD agreed well, showing a monotonic increase in rebound time up to a saturation point for increased therapy dose. In a second experiment, a thin layer of red blood cells (RBC) was added to the phantom to allow quantification of the fractionation of the RBC layer to compare with BCD metrics. A strong linear correlation was observed between the fractionation level and the time to BCD peak rebound velocity over histotripsy treatment. Finally, the correlation between BCD feedback and histotripsy tissue fractionation was validated in ex vivo porcine liver evaluated histologically. BCD metrics showed strong linear correlation with fractionation progression, suggesting that BCD provides useful quantitative real-time feedback on histotripsy treatment progression. |
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Histotripsy methods in mechanical disintegration of tissue: Toward clinical applications Khokhlova, V.A., J.B. Fowlkes, W.W. Roberts, G.R. Schade, Z. Xu, T.D. Khokhlova, T.L. Hall, A.D. Maxwell, Y.-N. Wang, and C.A. Cain, "Histotripsy methods in mechanical disintegration of tissue: Toward clinical applications," Int. J. Hypertherm., 31, 145-162, doi:10.3109/02656736.2015.1007538, 2015. |
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1 Mar 2015 ![]() |
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In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign prostatic hyperplasia (BPH), liver and kidney tumours, kidney stone fragmentation, enhancing anti-tumour immune response, and tissue decellularisation for regenerative medicine applications. Potential clinical advantages of the histotripsy methods are discussed. Histotripsy methods can be used to mechanically ablate a wide variety of tissues, whilst selectivity sparing structures such as large vessels. Both ultrasound and MR imaging can be used for targeting and monitoring the treatment in real time. Although the two approaches utilise different mechanisms for tissue disintegration, both have many of the same advantages and offer a promising alternative method of non-invasive surgery. |
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Fragmentation of urinary calculi in vitro by burst wave lithotripsy Maxwell, A.D., B.W. Cunitz, W. Kreider, O.A. Sapozhnikov, R.S. Hsi, J.D. Harper, M.R. Bailey, and M.D. Sorensen, "Fragmentation of urinary calculi in vitro by burst wave lithotripsy," J. Urol., 193, 338-344, doi:10.1016/j.juro.2014.08.009, 2015. |
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1 Jan 2015 ![]() |
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Development and testing of an image-guided prototype system for the comminution of kidney stones using burst wave lithotripsy Cunitz, B., A. Maxwell, W. Kreider, O. Sapozhnikov, F. Lee, J. Harper, M. Sorenson, and M. Bailey, "Development and testing of an image-guided prototype system for the comminution of kidney stones using burst wave lithotripsy," J. Acoust. Soc. Am., 136, 2193, doi:10.1121/1.4899951, 2014. |
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1 Oct 2014 ![]() |
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Burst wave lithotripsy is a novel technology that uses focused, sinusoidal bursts of ultrasound to fragment kidney stones. Prior research laid the groundwork to design an extracorporeal, image-guided probe for in-vivo testing and potentially human clinical testing. Toward this end, a 12-element 330 kHz array transducer was designed and built. The probe frequency, geometry, and shape were designed to break stones up to 1 cm in diameter into fragments <2 mm. A custom amplifier capable of generating output bursts up to 3 kV was built to drive the array. To facilitate image guidance, the transducer array was designed with a central hole to accommodate co-axial attachment of an HDI P4-2 probe. Custom B-mode and Doppler imaging sequences were developed and synchronized on a Verasonics ultrasound engine to enable real-time stone targeting and cavitation detection, Preliminary data suggest that natural stones will exhibit Doppler %u201Ctwinkling%u201D artifact in the BWL focus and that the Doppler power increases as the stone begins to fragment. This feedback allows accurate stone targeting while both types of imaging sequences can also detect cavitation in bulk tissue that may lead to injury. |
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Noninvasive ureterocele puncture using pulsed focused ultrasound: An in vitro study Maxwell, A.D., R.S. Hsi, M.R. Bailey, P. Casale, and T.S. Lendvay, "Noninvasive ureterocele puncture using pulsed focused ultrasound: An in vitro study," J. Endourol., 28, 342-346, doi:10.1098/end.2013.0528, 2014. |
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1 Mar 2014 ![]() |
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Purpose: To evaluate the feasibility of performing noninvasive puncture of pediatric ureteroceles with cavitation-based focused ultrasound (US) (histotripsy). |
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Addressing nonlinear propagation effects in characterization of high intensity focused ultrasound fields and prediction of thermal and mechanical bioeffects in tissue Khokhlova, V.A., P.V. Yuldashev, W. Kreider, O.A. Sapozhnikov, M.R. Bailey, T.D. Khokhlova, A.D. Maxwell, and L.A. Crum, "Addressing nonlinear propagation effects in characterization of high intensity focused ultrasound fields and prediction of thermal and mechanical bioeffects in tissue," J. Acoust. Soc. Am., 134, 4153, doi:10.1121/1.4831221, 2013. |
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1 Nov 2013 ![]() |
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Nonlinear propagation effects are present in most fields generated by high intensity focused ultrasound (HIFU) sources. In some newer HIFU applications, these effects are strong enough to result in the formation of high amplitude shocks that actually determine the therapy and provide a means for imaging. However, there is no standard approach yet accepted to address these effects. Here, a set of combined measurement and modeling methods to characterize nonlinear HIFU fields in water and predict acoustic pressures in tissue is presented. A characterization method includes linear acoustic holography measurements to set a boundary condition to the model and nonlinear acoustic simulations in water for increasing pressure levels at the source. A derating method to determine nonlinear focal fields with shocks in situ is based on the scaling of the source pressure for data obtained in water to compensate for attenuation losses in tissue. The accuracy of the methods is verified by comparing the results with hydrophone and time-to-boil measurements. Major effects associated with the formation of shocks are overviewed. A set of metrics for determining thermal and mechanical bioeffects is introduced and application of the proposed tools to strongly nonlinear HIFU applications is discussed. |
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Fragmentation of kidney stones in vitro by focused ultrasound bursts without shock waves Maxwell, A.D., B.W. Cunitz, W. Kreider, O.A. Sapozhnikov, R.S. Hsi, M.D. Sorensen, J.D. Harper, and M.R. Bailey, "Fragmentation of kidney stones in vitro by focused ultrasound bursts without shock waves," J. Acoust. Soc. Am., 134, 4183, doi:10.1121/1.4831340, 2013. |
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1 Nov 2013 ![]() |
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Shock wave lithotripsy (SWL) is the most common procedure for treatment of kidney stones. SWL noninvasively delivers high-energy focused shocks to fracture stones into passable fragments. We have recently observed that lower-amplitude, sinusoidal bursts of ultrasound can generate similar fracture of stones. This work investigated the characteristics of stone fragmentation for natural (uric acid, struvite, calcium oxalate, and cystine) and artificial stones treated by ultrasound bursts. Stones were fixed in position in a degassed water tank and exposed to 10-cycle bursts from a 200-kHz transducer with a pressure amplitude of p ≤ 6.5 MPa, delivered at a rate of 40200 Hz. Exposures caused progressive fractures in the stone surface leading to fragments up to 3 mm. Treatment of artificial stones at different frequencies exhibited an inverse relationship between the resulting fragment sizes and ultrasound frequency. All artificial and natural types of stones tested could be fragmented, but the comminution rate varied significantly with stone composition over a range of 12630 mg/min. These data suggest that stones can be controllably fragmented by sinusoidal ultrasound bursts, which may offer an alternative treatment strategy to SWL. |
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Holography and numerical projection methods for characterizing the three-dimensional acoustic fields of arrays in continuous-wave and transient regimes Kreider, W., A.D. Maxwell, P.V. Yuldashev, B.W. Cunitz, B. Dunmire, O.A. Sapozhnikov, and V.A. Khokhlova, "Holography and numerical projection methods for characterizing the three-dimensional acoustic fields of arrays in continuous-wave and transient regimes," J. Acoust. Soc. Am., 134, 4153, doi:10.1121/1.4831222, 2013. |
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1 Nov 2013 ![]() |
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The use of projection methods is increasingly accepted as a standard way of characterizing the 3D fields generated by medical ultrasound sources. When combined with hydrophone measurements of pressure amplitude and phase over a surface transverse to the wave propagation, numerical projection can be used to reconstruct 3D fields that account for operational details and imperfections of the source. Here, we use holography measurements to characterize the fields generated by two array transducers with different geometries and modes of operation. First, a seven-element, high-power therapy transducer is characterized in the continuous-wave regime using holography measurements and nonlinear forward-projection calculations. Second, a C5-2 imaging probe (Philips Healthcare) with 128 elements is characterized in the transient regime using holography measurements and linear projection calculations. Results from the numerical projections for both sources are compared with independent hydrophone measurements of select waveforms, including shocked focal waveforms for the therapy transducer. Accurate 3D field representations have been confirmed, though a notable sensitivity to hydrophone calibrations is revealed. Uncertainties associated with this approach are discussed toward the development of holography measurements combined with numerical projections as a standard metrological tool. |
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Kidney stone fracture by surface waves generated with focused ultrasound tone bursts Sapozhnikov, O.A., A.D. Maxwell, W. Kreider, B.W. Cunitz, and M.R. Bailey, "Kidney stone fracture by surface waves generated with focused ultrasound tone bursts," J. Acoust. Soc. Am., 134, 4184, doi:10.1121/1.4831341, 2013. |
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1 Nov 2013 ![]() |
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Previous studies have provided insight into the physical mechanisms of stone fracture in shock wave lithotripsy. Broadly focused shocks efficiently generate shear waves in the stone leading to internal tensile stresses, which in concert with cavitation at the stone surface, cause cracks to form and propagate. Here, we propose a separate mechanism by which stones may fragment from sinusoidal ultrasound bursts without shocks. A numerical elastic wave model was used to simulate propagation of tone bursts through a cylindrical stone at a frequency between 0.15 and 2 MHz. Results suggest that bursts undergo mode conversion into surface waves on the stone that continually create significant stresses well after the exposure is terminated. Experimental exposures of artificial cylindrical stones to focused burst waves in vitro produced periodic fractures along the stone surface. The fracture spacing and resulting fragment sizes corresponded well with the spacing of stresses caused by surface waves in simulation at different frequencies. These results indicate surface waves may be an important factor in fragmentation of stones by focused tone bursts and suggest that the resulting stone fragment sizes may be controlled by ultrasound frequency. |
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Rectified growth of histotripsy bubbles Kreider, W., A.D. Maxwell, T. Khokhlova, J.C. Simon, V.A. Khokhlova, O. Sapzhnikov, and M.R. Bailey, "Rectified growth of histotripsy bubbles," Proc., Meetings on Acoustics, 19, 075035, doi:10.1121/1.4800326, 2013. |
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Histotripsy treatments use high-amplitude shock waves to fractionate tissue. Such treatments have been demonstrated using both cavitation bubbles excited with microsecond-long pulses and boiling bubbles excited for milliseconds. A common feature of both approaches is the need for bubble growth, where at 1 MHz cavitation bubbles reach maximum radii on the order of 100 microns and boiling bubbles grow to about 1 mm. To explore how histotripsy bubbles grow, a model of a single, spherical bubble that accounts for heat and mass transport was used to simulate the bubble dynamics. Results suggest that the asymmetry inherent in nonlinearly distorted waveforms can lead to rectified bubble growth, which is enhanced at elevated temperatures. Moreover, the rate of this growth is sensitive to the waveform shape, in particular the transition from the peak negative pressure to the shock front. Current efforts are focused on elucidating this behavior by obtaining an improved calibration of measured histotripsy waveforms with a fiber-optic hydrophone, using a nonlinear propagation model to assess the impact on the focal waveform of higher harmonics present at the source's surface, and photographically observing bubble growth rates. |
In The News
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Move it along: Ultrasound to rid kidney stones sans surgery UW Health Sciences NewsBeat, Samantha Sauer Every year, more than a half-million people in the United States go to the emergency room for kidney stones. The common condition leads to hundreds of thousands of surgeries each year. |
12 Jan 2016
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Inventions
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Ultrasound System for Shearing Cellular Material in a Microplate Patent Number: 10,809,166 |
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20 Oct 2020
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Disclosed embodiments include illustrative piezoelectric element array assemblies, methods of fabricating a piezoelectric element array assembly, and systems and methods for shearing cellular material. Given by way of non-limiting example, an illustrative piezoelectric element array assembly includes at least one piezoelectric element configured to produce ultrasound energy responsive to amplified driving pulses. A lens layer is bonded to the at least one piezoelectric element. The lens layer has a plurality of lenses formed therein that are configured to focus ultrasound energy created by single ones of the at least one piezoelectric element into a plurality of wells of a microplate disposable in ultrasonic communication with the lens layer, wherein more than one of the plurality of lenses overlie single ones of the at least one piezoelectric element. |
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Method and System for MRI-based Targeting, Monitoring, and Quantification of Thermal and Mechanical Bioeffects in Tissue Induced by High Intensity Focused Ultrasound Example embodiments of system and method for magnetic resonance imaging (MRI) techniques for planning, real-time monitoring, control, and post-treatment assessment of high intensity focused ultrasound (HIFU) mechanical fractionation of biological material are disclosed. An adapted form of HIFU, referred to as "boiling histotripsy" (BH), can be used to cause mechanical fractionation of biological material. In contrast to conventional HIFU, which cause pure thermal ablation, BH can generate therapeutic destruction of biological tissue with a degree of control and precision that allows the process to be accurately measured and monitored in real-time as well as the outcome of the treatment can be evaluated using a variety of MRI techniques. Real-time monitoring also allow for real-time control of BH. Patent Number: 10,694,974 Vera Khokhlova, Wayne Kreider, Adam Maxwell, Yak-Nam Wang, Mike Bailey |
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30 Jun 2020
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Broadly Focused Ultrasonic Propulsion Probes, Systems, and Methods Disclosed herein are ultrasonic probes and systems incorporating the probes. The probes are configured to produce an ultrasonic therapy exposure that, when applied to a kidney stone, will exert an acoustic radiation force sufficient to produce ultrasonic propulsion. Unlike previous probes configured to produce ultrasonic propulsion, however, the disclosed probes are engineered to produce a relatively large (both wide and long) therapy region effective to produce ultrasonic propulsion. This large therapy region allows the probe to move a plurality of kidney stones (or fragments from lithotripsy) in parallel, thereby providing the user the ability to clear several stones from an area simultaneously. This "broadly focused" probe is, in certain embodiments, combined in a single handheld unit with a typical ultrasound imaging probe to produce real-time imaging. Methods of using the probes and systems to move kidney stones are also provided. Patent Number: 10,667,831 Mike Bailey, Bryan Cunitz, Barbrina Dunmire, Adam Maxwell, Oren Levy |
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2 Jun 2020
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Systems and Methods for Measuring Pressure Distributions of Acoustic Beams from Ultrasound Sources The present technology relates generally to receiving arrays to measure a characteristic of an acoustic beam and associated systems and methods. Patent Number: 10,598,773 Oleg Sapozhnikov, Wayne Kreider, Adam Maxwell, Vera Khokhlova |
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24 Mar 2020
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The present technology relates generally to receiving arrays to measure a characteristic of an acoustic beam and associated systems and methods. The receiving arrays can include elongated elements having at least one dimension, such as a length, that is larger than a width of an emitted acoustic beam and another dimension, such as a width, that is smaller than half of a characteristic wavelength of an ultrasound wave. The elongated elements can be configured to capture waveform measurements of the beam based on a characteristic of the emitted acoustic beam as the acoustic beam crosses a plane of the array, such as a transverse plane. The methods include measuring at least one characteristic of an ultrasound source using an array-based acoustic holography system and defining a measured hologram at the array surface based, at least in part, on the waveform measurements. The measured hologram can be processed to reconstruct a characteristic of the ultrasound source. The ultrasound source can be calibrated and/or re-calibrated based on the characteristic. |
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Focused Ultrasound Apparatus and Methods of Use Patent Number: 10,350,439 |
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16 Jul 2019
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Methods for diagnosing a pathologic tissue membrane, as well as a focused ultrasound apparatus and methods of treatment are disclosed to perform ureterocele puncture noninvasively using focused ultrasound-generated cavitation or boiling bubbles to controllably erode a hole through the tissue. An example ultrasound apparatus may include (a) a therapy transducer having a treatment surface, wherein the therapy transducer comprises a plurality of electrically isolated sections, (b) at least one concave acoustic lens defining a therapy aperture in the treatment surface of the therapy transducer, (c) an imaging aperture defined by either the treatment surface of the therapy transducer or by the at least one concave acoustic lens and (d) an ultrasound imaging probe axially aligned with a central axis of the therapy aperture. |
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Device and Method to Break Urinary Stones in Pets Record of Invention Number: 48640 Mike Bailey, Dan Leotta, Elizabeth Lynch, Brian MacConaghy, Adam Maxwell |
Disclosure
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28 May 2019
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Method to Create Patterns for Tissue Growth in Tissue Engineering Record of Invention Number: 48638 |
Disclosure
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28 May 2019
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Tractor Beam Array to Move Kidney Stones Record of Invention Number: 48636 |
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28 May 2019
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Noninvasive Fragmentation of Urinary Tract Stones with Focused Ultrasound Patent Number: 10,251,657 Adam Maxwell, Mike Bailey, Bryan Cunitz, Wayne Kreider, Oleg Sapozhnikov |
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9 Apr 2019
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Methods, computing devices, and a computer-readable medium are described herein related to fragmenting or comminuting an object in a subject using a burst wave lithotripsy (BWL) waveform. A computing device, such a computing device coupled to a transducer, may carry out functions for producing a BWL waveform. The computing device may determine a burst frequency for a number of bursts in the BWL waveform, where the number of bursts includes a number of cycles. Further, the computing device may determine a cycle frequency for the number of cycles. Yet further, the computing device may determine a pressure amplitude for the BWL waveform, where the pressure amplitude is less than or equal to 8 MPa. In addition, the computing device may determine a time period for producing the BWL waveform. |
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Time-reversal based ultrasound system for processing biological samples Record of Invention Number: 48375 |
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10 Jul 2018
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Targeting Methods and Devices for Non-invasive Therapy Delivery Record of Invention Number: 48305 Bryan Cunitz, Mike Bailey, Barbrina Dunmire, Michael Kennedy Hall, Adam Maxwell, Matthew Sorenson |
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11 Apr 2018
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Audio Feedback for Improving the Accuracy of BWL Targeting Record of Invention Number: 48254 Mike Bailey, Bryan Cunitz, Barbrina Dunmire, Christopher Hunter, Wayne Kreider, Adam Maxwell, Yak-Nam Wang |
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25 Jan 2018
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Pulse Amplifier for Driving Ultrasound Transducers Patent Number: 9,867,999 Adam Maxwell, Bryan Cunitz, Mike Bailey, Vera Khokhlova, Timothy Hall |
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16 Jan 2018
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Embodiments of the invention include improved radiofrequency (RF) pulse amplifier systems that incorporate an energy array comprising multiple capacitors connected in parallel. The energy array extends the maximum length of pulses and the maximum achievable peak power output of the amplifier when compared to similar systems. Embodiments also include systems comprising the amplifier configured to drive a load, wherein the load may include one or more ultrasound (e.g., piezoelectric) transducers Related methods of using the amplifier are also provided. |
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Holographic Beam Shaping for Ultrasound Therapy Transducers Record of Invention Number: 48221 |
Disclosure
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1 Dec 2017
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MRI-Guided Lithotripsy of Urinary Tract Stones Record of Invention Number: 47984 |
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23 Feb 2017
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Combination Burst Wave Lithotripsy and Ultrasonic Propulsion for Improved Stone Fragmentation Record of Invention Number: 47817 Adam Maxwell, Mike Bailey, Bryan Cunitz, Annie Zwaschka |
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9 Sep 2016
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Methods and Devices for Improved Cavitation-Induced Drug Delivery Using Pulsed Focused Ultrasound with Shocks Record of Invention Number: 47734 Vera Khokhlova, Joo Ha Hwang, Tatiana Khokhlova, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov |
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1 Jun 2016
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One-dimensional Receiving Arrays to Measure 2D Lateral Pressure Distribution of Acoustic Beams Radiated by Ultrasound Sources Record of Invention Number: 47632 Oleg Sapozhnikov, Vera Khokhlova, Wayne Kreider, Adam Maxwell |
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22 Feb 2016
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Novel Probe and Workflow for Ultrasonic Propulsion Record of Invention Number: 47322 Mike Bailey, Bryan Cunitz, Brian Dickinson, Barbrina Dunmire, Brian MacConaghy, Adam Maxwell |
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1 May 2015
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Noninvasive Disintegration of Peyronie's Plaque with Focused Ultrasound Record of Invention Number: 47233 Hunter Wessells, Mike Bailey, Mahri Haider, Tatiana Khokhlova, Frank Lee, Adam Maxwell, George Schade, Yak-Nam Wang |
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23 Feb 2015
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Method for In Vivo Diagnosis of Kidney Stone Composition Record of Invention Number: 47079 Adam Maxwell, Bryan Cunitz, Ryan Hsi |
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6 Oct 2014
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Methods to Determine Optimal Ultrasound Pulse Parameters to Fragment Urinary Calculi Using Acoustic Feedback Record of Invention Number: 47078 |
Disclosure
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6 Oct 2014
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Ultrasound Image Feedback for Lithotripsy Record of Invention Number: 47077 Adam Maxwell, Mike Bailey, Bryan Cunitz, Wayne Kreider, Oleg Sapozhnikov |
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6 Oct 2014
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Ultrasound Technique for Trapping and Displacing Solid Objects Using a Vortex Acoustic Beam Created by a Multi-element Sector Array Transducer Record of Invention Number: 47037 |
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18 Aug 2014
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Ultrasound Instrumentation for Ureteroscopic and Transcutaneous Kidney Stone Removal Record of Invention Number: 46839 Thomas Lendvay, Mike Bailey, Ryan Hsi, Brian MacConaghy, Adam Maxwell |
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4 Feb 2014
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MRI-based Methods to Target, Monitor, and Quantify Thermal and Mechanical Bioeffects in Tissue Induced by High Intensity Focused Ultrasound Record of Invention Number: 46745 Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Donghoon Lee, Adam Maxwell, George Schade |
Disclosure
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26 Nov 2013
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Methods to Selectively Fragment and Remove Tissue While Sparing Extracellular Matrix, Vessels and Similar Structures Using Microsecond-long High Intensity Focused Ultrasound Pulses with Shocks Record of Invention Number: 46742 Yak-Nam Wang, Mike Bailey, Vera Khokhlova, Tanya Khokhlova, Wayne Kreider, Adam Maxwell |
Disclosure
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18 Nov 2013
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Methods to Induce Large Volumes of Mechanically Fractionated Lesions Using Therapeutic Phased Arrays Record of Invention Number: 46733 Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov |
Disclosure
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8 Nov 2013
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Low-Frequency Enhancement of Boiling Histotripsy Record of Invention Number: 46730 Vera Khokhlova, Mike Bailey, Tanya Khokhlova, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov |
Disclosure
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7 Nov 2013
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Method to Induce Transcostal Tissue Ablation using High Intensity Focused Ultrasound with Shocks Record of Invention Number: 46728 Vera Khokhlova, Mike Bailey, Larry Crum, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov, Leonid R. Gavrilov, Petr Yuldashev |
Disclosure
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6 Nov 2013
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Device and Procedure for Noninvasive Removal of Ureteral Stents Record of Invention Number: 46501 Adam Maxwell, Mike Bailey, Ryan Hsi, Hunter Wessells |
Disclosure
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9 May 2013
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Noninvasive Fragmentation of Urinary Tract Stones with Focused Ultrasound Record of Invention Number: 46460 Adam Maxwell, Mike Bailey, Bryan Cunitz, Ryan Hsi |
Disclosure
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28 Mar 2013
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Noninvasive Treatment of Ureteroceles with Focused Ultrasound Record of Invention Number: 46404 Mike Bailey, Pasquale Casale, Ryan Hsi, Thomas Lendvay, Adam Maxwell |
Disclosure
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14 Feb 2013
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Method for Noninvasive Focused Ultrasound Surgery Record of Invention Number: 46356 |
Disclosure
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11 Jan 2013
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