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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

Elastic properties of aging human hematoma model in vitro and its susceptibility to histotripsy liquefaction

Ponomarchuk, E.M., and 12 others including T.D. Khokhlova, O.A. Sapozhnikov, and V.A. Khokhlova, "Elastic properties of aging human hematoma model in vitro and its susceptibility to histotripsy liquefaction," Ultrasound Med. Biol., 50, 927-938, doi:10.1016/j.ultrasmedbio.2024.02.019, 2024.

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1 Jun 2024

Tissue susceptibility to histotripsy disintegration has been reported to depend on its elastic properties. This work was aimed at investigation of histotripsy efficiency for liquefaction of human hematomas, depending on their stiffness and degree of retraction over time (0–10 d).

It was found that clotting time decreased from 113 to 25 min with the increase in blood temperature from 10°C to 37°C. The shear modulus increased to 0.53 ± 0.17 kPa during clotting and remained constant within 8 d of incubation at 2°C. Sample volumes decreased by 57% because of retraction within 10 d. SEM revealed significant echinocytosis but unchanged ultrastructure of the fibrin meshwork. Liquefaction rate and lesion dimensions produced with the same histotripsy protocols correlated with the increase in the degree of retraction and were lower in retracted samples versus freshly clotted samples. More than 80% of residual fibrin fragments after histotripsy treatment were shorter than 150 μm; the maximum length was 208 μm, allowing for unobstructed aspiration of the lysate with most clinically used needles.

The results indicate that hematoma susceptibility to histotripsy liquefaction is not entirely determined by its stiffness, and correlates with the retraction degree.

Treatment planning and aberration correction algorithm for HIFU ablation of renal tumors

Rosnitskiy, P.B., T.D. Khokhlova, G.R. Schade, O.A. Sapozhnikov, and V.A. Khokhlova, "Treatment planning and aberration correction algorithm for HIFU ablation of renal tumors," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 71, 341-353, doi:10.1109/TUFFC.2024.3355390, 2024.

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1 Mar 2024

High-intensity focused ultrasound (HIFU) applications for thermal or mechanical ablation of renal tumors often encounter challenges due to significant beam aberration and refraction caused by oblique beam incidence, inhomogeneous tissue layers, and presence of gas and bones within the beam. These losses can be significantly mitigated through sonication geometry planning, patient positioning, and aberration correction using multielement phased arrays. Here, a sonication planning algorithm is introduced, which uses the simulations to select the optimal transducer position and evaluate the effect of aberrations and acoustic field quality at the target region after aberration correction. Optimization of transducer positioning is implemented using a graphical user interface (GUI) to visualize a segmented 3-D computed tomography (CT)-based acoustic model of the body and to select sonication geometry through a combination of manual and automated approaches. An HIFU array (1.5 MHz, 256 elements) and three renal cell carcinoma (RCC) cases with different tumor locations and patient body habitus were considered. After array positioning, the correction of aberrations was performed using a combination of backpropagation from the focus with an ordinary least squares (OLS) optimization of phases at the array elements. The forward propagation was simulated using a combination of the Rayleigh integral and k-space pseudospectral method (k-Wave toolbox). After correction, simulated HIFU fields showed tight focusing and up to threefold higher maximum pressure within the target region. The addition of OLS optimization to the aberration correction method yielded up to 30% higher maximum pressure compared to the conventional backpropagation and up to 250% higher maximum pressure compared to the ray-tracing method, particularly in strongly distorted cases.

Enhancement of boiling histotripsy by steering the focus axially during the pulse delivery

Thomas, G.P.L., T.D. Khokhlova, O.A. Sapozhnikov, and V.A. Khokhlova, "Enhancement of boiling histotripsy by steering the focus axially during the pulse delivery," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 70, 865-875, doi:10.1109/TUFFC.2023.3286759, 2023.

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1 Aug 2023

Boiling histotripsy (BH) is a pulsed high-intensity focused ultrasound (HIFU) method relying on the generation of high-amplitude shocks at the focus, localized enhanced shock-wave heating, and bubble activity driven by shocks to induce tissue liquefaction. BH uses sequences of 1–20 ms long pulses with shock fronts of over 60 MPa amplitude, initiates boiling at the focus of the HIFU transducer within each pulse, and the remainder shocks of the pulse then interact with the boiling vapor cavities. One effect of this interaction is the creation of a prefocal bubble cloud due to reflection of shocks from the initially generated mm-sized cavities: the shocks are inverted when reflected from a pressure-release cavity wall resulting in sufficient negative pressure to reach intrinsic cavitation threshold in front of the cavity. Secondary clouds then form due to shock-wave scattering from the first one. Formation of such prefocal bubble clouds has been known as one of the mechanisms of tissue liquefaction in BH. Here, a methodology is proposed to enlarge the axial dimension of this bubble cloud by steering the HIFU focus toward the transducer after the initiation of boiling until the end of each BH pulse and thus to accelerate treatment. A BH system comprising a 1.5 MHz 256-element phased array connected to a Verasonics V1 system was used. High-speed photography of BH sonications in transparent gels was performed to observe the extension of the bubble cloud resulting from shock reflections and scattering. Volumetric BH lesions were then generated in ex vivo tissue using the proposed approach. Results showed up to almost threefold increase of the tissue ablation rate with axial focus steering during the BH pulse delivery compared to standard BH.

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Inventions

Transrectal Ultrasound Probe for Boiling Histotripsy Ablation of Prostate, and Associated Systems and Methods

Inventors: V. Khokhlova, P. Rosnitskiy (Seattle), P.V. Yuldashev (Moscow), T.D. Khokhlova (Seattle), O. Sapozhnikov, and G.R. Schade (Seattle)

Patent Number: 11,896,853

Vera Khokhlova, Oleg Sapozhnikov

Patent

13 Feb 2024

High Intensity Focused Ultrasound Systems for Treating Tissue

Inventors: Y.-N. Wang, M.R. Bailey, T.D. Khokhlova (Seattle), W. Kreider, A.D. Maxwell, G.R. Schade (Seattle), and V.A. Khokhlova

Patent Number: 11,857,813

Yak-Nam Wang, Mike Bailey, Wayne Kreider, Adam Maxwell, Vera Khokhlova

Patent

2 Jan 2024

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.

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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