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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

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

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.

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23 Mar 2017

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.

Publications

2000-present and while at APL-UW

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

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 (2–6 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, 2–6 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.

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

Rosnitskiy, P.B., P.V. Uldashev, O.A. Sapozhnikov, L.R. Gavrilov, and V.A. Khokhlova, "Simulation of nonlinear trans-skull focusing and formation of shocks in brain using a fully populated ultrasound array with aberration correction," J. Acoust. Soc. Am., 146, doi:10.1121/1.5126685 , 2019.

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1 Sep 2019

Multi-element high-intensity focused ultrasound phased arrays in the shape of hemispheres are currently used in clinics for thermal lesioning in deep brain structures. Certain side effects of overheating non-targeted tissues and skull bones have been revealed. Here, an approach is developed to mitigate these effects. A specific design of a fully populated 256-element 1-MHz array shaped as a spherical segment (F–number, F# = 1) and filled by randomly distributed equal-area polygonal elements is proposed. Capability of the array to generate high-amplitude shock fronts at the focus is tested in simulations by combining three numerical algorithms for linear and nonlinear field modeling and aberration correction. The algorithms are based on the combination of the Rayleigh integral, a linear pseudo-spectral time domain Kelvin–Voigt model, and nonlinear Westervelt model to account for the effects of inhomogeneities, aberrations, reflections, absorption, nonlinearity, and shear waves in the skull. It is shown that the proposed array can generate nonlinear waveforms with shock amplitudes >60 MPa at the focus deep inside the brain without exceeding the existing technical limitation on the intensity of 40 W/cm2 at the array elements. Such shock amplitudes are sufficient for mechanical ablation of brain tissues using the boiling histotripsy approach and implementation of other shock-based therapies.

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

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 1–10-ms long pulses with in situ shock amplitudes of 75–100 MPa at the focus and pulse repetition frequencies (PRFs) of 1–10 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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Inventions

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.

Imaging Bubbles in a Medium

Patent Number: 9,743,909

Oleg Sapozhnikov, Mike Bailey, Joo Ha Hwang, Tatiana Khokhlova, Vera Khokhlova, Tong Li, Matthew O'Donnell

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Patent

29 Aug 2017

A method for imaging a cavitation bubble includes producing a vibratory wave that induces a cavitation bubble in a medium, producing one or more detection waves directed toward the induced cavitation bubble, receiving one or more reflection waves, identifying a change in one or more characteristics of the induced cavitation bubble, and generating an image of the induced cavitation bubble using a computing device on the basis of the identified change in the one or more characteristics. The one or more received reflection waves correspond to at least one of the one or more produced detection waves reflection from the induced cavitation bubble. The identified change in one or more characteristics corresponds to the one or more received reflection waves.

Methods and Systems for Non-invasive Treatment of Tissue Using High Intensity Focused Ultrasound Therapy

Patent Number: 9,700,742

Michael Canney, Mike Bailey, Larry Crum, Joo Ha Hwang, Tatiana Khokhlova, Vera Khokhlova, Wayne Kreider, Oleg Sapozhnikov

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Patent

11 Jul 2017

Methods and systems for non-invasive treatment of tissue using high intensity focused ultrasound ("HIFU") therapy. A method of non-invasively treating tissue in accordance with an embodiment of the present technology, for example, can include positioning a focal plane of an ultrasound source at a target site in tissue. The ultrasound source can be configured to emit HIFU waves. The method can further include pulsing ultrasound energy from the ultrasound source toward the target site, and generating shock waves in the tissue to induce boiling of the tissue at the target site within milliseconds. The boiling of the tissue at least substantially emulsifies the tissue.

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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