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Vera Khokhlova

Senior Principal Engineer

Email

verak2@uw.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

Dual-mode 1D linear ultrasound array for image-guided drug delivery enhancement without ultrasound contrast agents

Williams, R.P., M.M. Karzova, P.V. Yuldashev, A.Z. Kaloev, F.A. Nartov, V.A. Khokhlova, B.W. Cunitz, K.P. Morrison, and T.D. Khokhlova, "Dual-mode 1D linear ultrasound array for image-guided drug delivery enhancement without ultrasound contrast agents," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, EOR, doi:10.1109/TUFFC.2023.3268603, 2023.

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19 Apr 2023

Pulsed high-intensity focused ultrasound (pHIFU) uses nonlinearly distorted millisecond-long ultrasound pulses of moderate intensity to induce inertial cavitation in tissue without administration of contrast agents. The resulting mechanical disruption permeabilizes the tissue and enhances the diffusion of systemically administered drugs. This is especially beneficial for tissues with poor perfusion such as pancreatic tumors. Here we characterize the performance of a dual-mode ultrasound array designed for image-guided pHIFU therapies in producing inertial cavitation and ultrasound imaging. The 64-element linear array (1.071 MHz, aperture of 14.8 mm x 51.2 mm, and pitch of 0.8 mm) with elevational focal length of 50 mm was driven by the Verasonics V-1 ultrasound system with extended burst option. The attainable focal pressures and electronic steering range in linear and nonlinear operating regimes (relevant to pHIFU treatments) were characterized through hydrophone measurements, acoustic holography, and numerical simulations. The steering range at ±10% from the nominal focal pressure was found to be ±±6 mm axially and ±11 mm azimuthally. Focal waveforms with shock fronts of up to 45 MPa, and peak negative pressures up to 9 MPa were achieved at focusing distances of 38–75 mm from the array. Cavitation behaviors induced by isolated 1 ms pHIFU pulses in optically transparent agarose gel phantoms were observed by high-speed photography across a range of excitation amplitudes and focal distances. For all focusing configurations the appearance of sparse, stationary cavitation bubbles occurred at the same P_ threshold of 2 MPa. As the output level increased, a qualitative change in cavitation behavior occurred, to pairs and sets of proliferating bubbles. The pressure P_ at which this transition was observed corresponded to substantial nonlinear distortion and shock formation in the focal region and was thus dependent on the focal distance of the beam ranging within 3–4 MPa for azimuthal F-numbers of 0.74 to 1.5. The array was capable of B-mode imaging at 1.5 MHz of centimeter-sized targets in phantoms and in vivo pig tissues at depths of 3 cm to 7 cm, relevant to pHIFU applications in abdominal targets.

Quantitative assessment of boiling histotripsy progression based on color Doppler measurements

Song, M.H., G.P.L. Thomas, V.A. Khokhlova, O.A. Sapozhnikov, M.R. Bailey, A.D. Maxwell, P.V. Yuldashev, and T.D. Khokhlova, "Quantitative assessment of boiling histotripsy progression based on color Doppler measurements," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 69, 3255-3269, doi:10.1109/TUFFC.2022.3212266, 2022.

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1 Dec 2022

Boiling histotripsy (BH) is a mechanical tissue liquefaction method that uses sequences of millisecond-long high intensity focused ultrasound (HIFU) pulses with shock fronts. The BH treatment generates bubbles that move within the sonicated volume due to acoustic radiation force. Since the velocity of the bubbles and tissue debris is expected to depend on the lesion size and liquefaction completeness, it could provide a quantitative metric of the treatment progression. In this study, the motion of bubble remnants and tissue debris immediately following BH pulses was investigated using high-pulse repetition frequency (PRF) plane-wave color Doppler ultrasound in ex vivo myocardium tissue. A 256-element 1.5 MHz spiral HIFU array with a coaxially integrated ultrasound imaging probe (ATL P4-2) produced 10 ms BH pulses to form volumetric lesions with electronic beam steering. Prior to performing volumetric BH treatments, the motion of intact myocardium tissue and anticoagulated bovine blood following isolated BH pulses was assessed as two limiting cases. In the liquid blood the velocity of BH-induced streaming at the focus reached over 200 cm/s, whereas the intact tissue was observed to move toward the HIFU array consistent with elastic rebound of tissue. Over the course of volumetric BH treatments tissue motion at the focus locations was dependent on the axial size of the forming lesion relative to the corresponding size of the HIFU focal area. For axially small lesions, the maximum velocity after the BH pulse was directed toward the HIFU transducer and monotonically increased over time from about 20–100 cm/s as liquefaction progressed, then saturated when tissue was fully liquefied. For larger lesions obtained by merging multiple smaller lesions in the axial direction, the high-speed streaming away from the HIFU transducer was observed at the point of full liquefaction. Based on these observations, the maximum directional velocity and its location along the HIFU propagation axis were proposed and evaluated as candidate metrics of BH treatment completeness.

In vivo aberration correction for transcutaneous HIFU therapy using a multielement array

Thomas, G.P.L., T.D. Khokhlova, O.A. Sapozhnikov, Y.-N. Wang, S.I. Totten, and V.A. Khokhlova, "In vivo aberration correction for transcutaneous HIFU therapy using a multielement array," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 69, 2955-2965, doi:10.1109/TUFFC.2022.3200309, 2022.

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1 Oct 2022

One of the challenges of transcutaneous high-intensity focused ultrasound (HIFU) therapies, especially ones relying heavily on shock formation, such as boiling histotripsy (BH), is the loss of focusing from aberration induced by the heterogeneities of the body wall. Here, a methodology to execute aberration correction in vivo is proposed. A custom BH system consisting of a 1.5-MHz phased array of 256 elements connected to a Verasonics V1 system is used in pulse/echo mode on a porcine model under general anesthesia. Estimation of the time shifts needed to correct for aberration in the liver and kidney is done by maximizing the value of the coherence factor on the acquired backscattered signals. As this process requires multiple pulse/echo sequences on a moving target to converge to a solution, tracking is also implemented to ensure that the same target is used between each iteration. The method was validated by comparing the acoustic power needed to generate a boiling bubble at one target with aberration correction and at another target within a 5-mm radius without aberration correction. Results show that the aberration correction effectively lowers the acoustic power required to reach boiling by up to 45%, confirming that it indeed restored formation of the nonlinear shock front at the focus.

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Inventions

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

Patent Number: 11,224,356

Wayne Kreider, Vera Khokhlova

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Patent

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

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.

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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