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Vera Khokhlova

Senior Principal Engineer

Email

vera@apl.washington.edu

Phone

206-221-6585

Education

M.S. Physics, Moscow State University, 1986

Ph.D. Acoustics, Moscow State University, 1991

Videos

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

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.

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

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.

The method was proposed at APL-UW in collaboration with Moscow State University (Russia) and now is being evaluated for various clinical applications. It has particular promise because of its important clinical advantages: the treatment of tissue volumes can be accelerated while sparing adjacent structures and not injuring intervening tissues; it generates precisely controlled mechanical lesions with sharp margins; the method can be implemented in existing clinical systems; and it can be used with real-time ultrasound imaging for targeting, guidance, and evaluation of outcomes. In addition, compared to thermal ablation, BH may lead to faster resorption of the liquefied lesion contents.

Characterizing Medical Ultrasound Sources and Fields

For every medical ultrasound transducer it's important to characterize the field it creates, whether for safety of imaging or efficacy of therapy. CIMU researchers measure a 2D acoustic pressure distribution in the beam emanating from the source transducer and then reconstruct mathematically the exact field on the surface of the transducer and in the entire 3D space.

11 Sep 2017

Publications

2000-present and while at APL-UW

A prototype therapy system for boiling histotripsy in abdominal targets based on a 256-element spiral array

Bawiec, C.R., T.D. Khokhlova, O.A Sapozhnikov, P.B. Rosnitskiy, B.W. Cunitz, M.A. Ghanem, C. Hunter, W. Kreider, G.R. Schade, P.V. Yuldashev, and V.A. Khokhlova, "A prototype therapy system for boiling histotripsy in abdominal targets based on a 256-element spiral array," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 68, 1496-1510, doi:10.1109/TUFFC.2020.3036580, 2021.

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1 May 2021

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

Phase-aberration correction for HIFU therapy using a multielement array and backscattering of nonlinear pulses

Thomas, G.P.L., T.D. Khokhlova, C.R. Bawiec, A.T. Peek, O.A. Sapozhnikov, M. O'Donnell, and V.A. Khokhlova, "Phase-aberration correction for HIFU therapy using a multielement array and backscattering of nonlinear pulses," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 68, 1040-1050, doi:0.1109/TUFFC.2020.3030890, 2021.

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1 Apr 2021

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

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

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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Inventions

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

Patent

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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Patent

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.

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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Patent

16 Jan 2018

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.

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
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