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Wayne Kreider

Senior Engineer






Bachelor of Science Engineering Science & Mechanics, Virginia Tech, 1993

Master of Science Engineering Mechanics, Virginia Tech, 1995

Doctor of Philosophy Bioengineering, University of Washington, 2008


2000-present and while at APL-UW

Development of tough hydrogel phantoms to mimic fibrous tissue for focused ultrasound therapies

Kumar, Y.N., Z. Singh, Y.-N. Wang, G.R. Schade, W. Kreider, M. Bruce, E. Vlaisavljevich, T.D. Khokhlova, and A.D. Maxwell, "Development of tough hydrogel phantoms to mimic fibrous tissue for focused ultrasound therapies," Ultrasound Biol. Med., 48, 1762-1777, doi:10.1016/j.ultrasmedbio.2022.05.002, 2022.

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1 Sep 2022

Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffness of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate. The stiffness was established using shear wave elastography (SWE) and indentometry techniques and was found to be representative of human BPH ex vivo prostate tissue. Different phantom compositions and excised ex vivo BPH tissue samples were treated with a 700-kHz histotripsy transducer at different pulse repetition frequencies. Post-treatment, the hybrid gels and the tissue samples exhibited differential reduction in stiffness as measured by SWE. On B-mode ultrasound, partially treated areas were present as hyperechoic zones and fully liquified areas as hypoechoic zones. Phase contrast microscopy of the gel samples revealed liquefaction in regions consistent with the target lesion dimensions and correlated to findings identified in tissue samples via histology. The dose required to achieve liquefaction in the hybrid gel was similar to what has been observed in ex vivo tissue and greater than that of agarose of comparable or higher Young's modulus by a factor >10. These results indicate that the developed hydrogels closely mimic elasticities found in BPH prostate ex vivo tissue and have a similar response to histotripsy treatment, thus making them a useful cost-effective alternative for developing and evaluating different treatment protocols.

Improving burst wave lithotripsy effectiveness for small stones and fragments by increasing frequency: Theoretical modeling and ex vivo study

Bailey, M.R., A.D. Maxwell, S. Cao, S. Ramesh, Z. Liu, J.C. Williams, J. Thiel, B. Dunmire, T. Colonius, E. Kuznetsova, W. Kreider, M.D. Sorensen, J.E. Lindeman, and O.A. Sapozhnikov, "Improving burst wave lithotripsy effectiveness for small stones and fragments by increasing frequency: Theoretical modeling and ex vivo study," J. Endourol., 36, doi:10.1089/end.2021.0714, 2022.

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5 Jul 2022

Introduction and Objective: In clinical trial NCT03873259, a 2.6-mm lower pole stone was treated transcutaneously and ex vivo with 390-kHz burst wave lithotripsy (BWL) for 40 minutes and failed to break. The stone was subsequently fragmented with 650-kHz BWL after a 4-minute exposure. This study investigated how to fragment small stones and why varying the BWL frequency may more effectively fragment stones to dust.

Methods: A linear elastic theoretical model was used to calculate the stress created inside stones from shock wave lithotripsy (SWL) and different BWL frequencies mimicking the stone's size, shape, lamellar structure, and composition. To test model predictions about the impact of BWL frequency, matched pairs of stones (1–5 mm) were treated at (1) 390 kHz, (2) 830 kHz, and (3) 390 kHz followed by 830 kHz. The mass of fragments > 1 and 2 mm was measured over 10 minutes of exposure.

Results: The linear elastic model predicts that the maximum principal stress inside a stone increases to more than 5.5 times the pressure applied by the ultrasound wave as frequency is increased, regardless of the composition tested. The threshold frequency for stress amplification is proportionate to the wave speed divided by the stone diameter. Thus, smaller stones may be likely to fragment at a higher frequency, but not at a lower frequency below a limit. Unlike with SWL, this amplification in BWL occurs consistently with spherical and irregularly shaped stones. In water tank experiments, stones smaller than the threshold size broke fastest at high frequency (p = 0.0003), whereas larger stones broke equally well to submillimeter dust at high, low, or mixed frequencies.

Conclusions: For small stones and fragments, increasing frequency of BWL may produce amplified stress in the stone causing the stone to break. Using the strategies outlined here, stones of all sizes may be turned to dust efficiently with BWL.

Design and characterization of an ultrasound transducer for combined histotripsy-thrombolytic therapy

Maxwell, A.D., K.J. Haworth, C.K. Holland, S.A. Hendley, W. Kreider, and K.B. Bader, "Design and characterization of an ultrasound transducer for combined histotripsy-thrombolytic therapy," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 69, 156-165, doi:10.1109/TUFFC.2021.3113635, 2022.

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1 Jan 2022

Chronic thrombi of the deep veins of the leg are resistant to dissolution or removal by current interventions and can act as thrombogenic sources. Histotripsy, a focused ultrasound therapy, uses the mechanical activity of bubble clouds to liquefy target tissues. In vitro experiments have shown that histotripsy enhances thrombolytic agent recombinant tissue plasminogen activator in a highly retracted clot model resistant to lytic therapy alone. Although these results are promising, further refinement of the acoustic source is necessary for in vivo studies and clinical translation. The source parameters for use in vivo were defined, and a transducer was fabricated for transcutaneous exposure of porcine and human iliofemoral deep-vein thrombosis (DVT) as the target. Based on the design criteria, a 1.5-MHz elliptical source with a 6-cm focal length and a focal gain of 60 was selected. The source was characterized by fiber-optic hydrophone and holography. High-speed photography showed that the cavitation cloud could be confined to dimensions smaller than the specified vessel lumen. The source was also demonstrated in vitro to create confined lesions within clots. The results support that this design offers an appropriate clinical prototype for combined histotripsy-thrombolytic therapy.

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MRI-Feedback Control of Ultrasound Based Mechanical Fractionation of Biological Tissue

Patent Number: 11,224,356

Wayne Kreider, Vera Khokhlova

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18 Jan 2022

Disclosed herein are example embodiments of devices, systems, and methods for mechanical fractionation of biological tissue using magnetic resonance imaging (MRI) feedback control. The examples may involve displaying an image representing first MRI data corresponding to biological tissue, and receiving input identifying one or more target regions of the biological tissue to be mechanically fractionated via exposure to first ultrasound waves. The examples may further involve applying the first ultrasound waves and, contemporaneous to or after applying the first ultrasound waves, acquiring second MRI data corresponding to the biological tissue. The examples may also involve determining, based on the second MRI data, one or more second parameters for applying second ultrasound waves to the biological tissue, and applying the second ultrasound waves to the biological tissue according to the one or more second parameters.

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


30 Jun 2020

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

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.

More Inventions

Acoustics Air-Sea Interaction & Remote Sensing Center for Environmental & Information Systems Center for Industrial & Medical Ultrasound Electronic & Photonic Systems Ocean Engineering Ocean Physics Polar Science Center