Tatiana Khokhlova tdk7@uw.edu Phone 206-543-6193 |
Publications |
2000-present and while at APL-UW |
Histotripsy: A method for mechanical tissue ablation with ultrasound Xu, Z., T.D. Khokhlova, C.S. Cho, and V.A. Khokhlova, "Histotripsy: A method for mechanical tissue ablation with ultrasound," Ann. Rev. Biomed. Eng., 26, 141-167, doi:10.1146/annurev-bioeng-073123-022334, 2024. |
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1 Jul 2024 |
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Histotripsy is a relatively new therapeutic ultrasound technology to mechanically liquefy tissue into subcellular debris using high-amplitude focused ultrasound pulses. In contrast to conventional high-intensity focused ultrasound thermal therapy, histotripsy has specific clinical advantages: the capacity for real-time monitoring using ultrasound imaging, diminished heat sink effects resulting in lesions with sharp margins, effective removal of the treated tissue, a tissue-selective feature to preserve crucial structures, and immunostimulation. The technology is being evaluated in small and large animal models for treating cancer, thrombosis, hematomas, abscesses, and biofilms; enhancing tumor-specific immune response; and neurological applications. Histotripsy has been recently approved by the US Food and Drug Administration to treat liver tumors, with clinical trials undertaken for benign prostatic hyperplasia and renal tumors. This review outlines the physical principles of various types of histotripsy; presents major parameters of the technology and corresponding hardware and software, imaging methods, and bioeffects; and discusses the most promising preclinical and clinical applications. |
Dynamic mode decomposition for transient cavitation bubbles imaging in pulsed high-intensity focused ultrasound therapy Song, M.H., O.A Sapozhnikov, V.A. Khokhlova, and T.D. Khokhlova, "Dynamic mode decomposition for transient cavitation bubbles imaging in pulsed high-intensity focused ultrasound therapy," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 71, 596-606, doi:10.1109/TUFFC.2024.3387351, 2024. |
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1 May 2024 |
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Pulsed high-intensity focused ultrasound (pHIFU) can induce sparse de novo inertial cavitation without the introduction of exogenous contrast agents, promoting mild mechanical disruption in targeted tissue. Because the bubbles are small and rapidly dissolve after each HIFU pulse, mapping transient bubbles and obtaining real-time quantitative metrics correlated with tissue damage are challenging. Prior work introduced Bubble Doppler, an ultrafast power Doppler imaging method as a sensitive means to map cavitation bubbles. The main limitation of that method was its reliance on conventional wall filters used in Doppler imaging and its optimization for imaging blood flow rather than transient scatterers. This study explores Bubble Doppler enhancement using dynamic mode decomposition (DMD) of a matrix created from a Doppler ensemble for mapping and extracting the characteristics of transient cavitation bubbles. DMD was first tested in silico with a numerical dataset mimicking the spatiotemporal characteristics of backscattered signal from tissue and bubbles. The performance of DMD filter was compared to other widely used Doppler wall filter-singular value decomposition (SVD) and infinite impulse response (IIR) high-pass filter. DMD was then applied to an ex vivo tissue dataset where each HIFU pulse was immediately followed by a plane wave Doppler ensemble. In silico DMD outperformed SVD and IIR high-pass filter and ex vivo provided physically interpretable images of the modes associated with bubbles and their corresponding temporal decay rates. These DMD modes can be trackable over the duration of pHIFU treatment using k-means clustering method, resulting in quantitative indicators of treatment progression. |
In The News
A mother-daughter team of physicists is advancing therapeutic ultrasound to break up tissue like kidney stones and tumors UW CoMotion, Charlotte Schubert In a vast basement lab at the Center for Industrial and Medical Ultrasound (CIMU), an arm of UW’s Applied Physics Lab, Vera and Tatiana Khokhlova pose beside their research poster, looking like any pair of senior and junior colleagues who are experts in their field and proud of their work. |
7 Mar 2024
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Inventions
Histotripsy Treatment of Hematoma A rapid, definitive intervention aiming at evacuation of the space-occupying hematoma would reduce pain, improve function, and avoid long term sequelae. Ultrasound is known to promote intravascular clot breakdown, as both a standalone procedure and used in conjunction with thrombolytic drugs and/or microbubbles. In-vitro and in-vivo studies have been conducted over the years, and acoustic cavitation is widely accepted as the dominant mechanism for mechanical disruption of the clot integrity and partial or complete recanalization of the vessel. Recently, a technique termed histotripsy that employs high-intensity focused ultrasound (HIFU) has been demonstrated to dissolve large in vitro and in vivo vascular clots without thrombolytic drugs within 1.5-5 minutes into debris 98% of which were smaller than 5 microns. However, this approach cannot be applied to the large extravascular hematomas due to their large volume (20-50 cc's) compared to intravascular clots, which necessitates much higher thrombolysis rates to complete the treatment within clinically relevant times (.about.15-20 minutes). Patent Number: 10,702,719 Tatiana Khokhlova, Tom Matula, Wayne Monsky, Yak-Nam Wang |
Patent
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7 Jul 2020
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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
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29 Aug 2017
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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
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11 Jul 2017
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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. |