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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

'HIFU Beam' A simulator for predicting axially symmetric nonlinear acoustic fields generated by focused transducers in a layered medium

Yuldashev, P.V., M.M. Karzova, W. Kreider, P.B. Rosnitskiy, O.A. Sapozhnikov, and V.A. Khokhlova, "'HIFU Beam' A simulator for predicting axially symmetric nonlinear acoustic fields generated by focused transducers in a layered medium," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 68, 2837-2852, doi:10.1109/TUFFC.2021.3074611, 2021.

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1 Sep 2021

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

Inertial cavitation behaviors induced by nonlinear focused ultrasound pulses

Bawiec, C.R., P.B. Rosnitskiy, A.T. Peek, A.D. Maxwell, W. Kreider, G.R. Ter Haar, O.A. Sapozhnikov, V.A. Khokhlova, and T.D. Khokhlova, "Inertial cavitation behaviors induced by nonlinear focused ultrasound pulses," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 68, 2884-2895, doi:10.1109/TUFFC.2021.3073347, 2021.

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1 Sep 2021

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

Introduction to the special issue on histotripsy: Approaches, mechanisms, hardware, and applications

Zhen, X., V.A. Khokhlova, K.A. Wear, J.-F. Aubry, and T.A. Bigelow, "Introduction to the special issue on histotripsy: Approaches, mechanisms, hardware, and applications," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 68, 2834-2836, doi:10.1109/TUFFC.2021.3102092, 2021.

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1 Sep 2021

Histotripsy is a therapeutic ultrasound technology to liquefy tissue into acellular debris using sequences of high-power focused ultrasound pulses. Research on histotripsy has been rapidly growing in the past decade; newer applications are being proposed and evaluated for clinical use. In contrast to conventional high-intensity focused ultrasound (HIFU) thermal therapy, the major mechanism of histotripsy is mechanical, which enables localized tissue disintegration at the target sites without thermal damage to overlying and surrounding tissues. Two major approaches, cavitational histotripsy and boiling histotripsy, with two different mechanisms, have been extensively explored lately. Histotripsy therapy is being evaluated for treating cancer, thrombosis, hematomas, abscess, neurological diseases, for inducing an enhanced immune response and performing noninvasive biopsy in preclinical studies with small and large animal models. The first clinical trials using histotripsy for benign prostatic hyperplasia, liver cancer, and calcified aortic stenosis have been undertaken.

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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.

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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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