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Yak-Nam Wang

Research Scientist Engineer - Principal

Email

ynwang@apl.washington.edu

Phone

206-616-6673

Education

B.S. Biomedical Materials Science & Engineering, Queen Mary & Westfield College, University of London, UK, 1996

Ph.D. Biomedical Materials, Queen Mary & Westfield College, University of London, UK, 2000

Videos

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.

Non-invasive Treatment of Abscesses with Ultrasound

Abscesses are walled-off collections of fluid and bacteria within the body. They are common complications of surgery, trauma, and systemic infections. Typical treatment is the surgical placement of a drainage catheter to drain the abscess fluid over several days. Dr. Keith Chan and researchers at APL-UW's Center for Industrial + Medical Ultrasound are exploring how to treat abscesses non-invasively, that is, from outside the body, with high-intensity focused ultrasound (HIFU). This experimental therapy could reduce pain, radiation exposure, antibiotic use, and costs for patients with abscesses. Therapeutic ultrasound could also treat abscesses too small or inaccessible for conventional drainage.

20 Jun 2016

Publications

2000-present and while at APL-UW

Advancing boiling histotripsy dose in ex vivo and in vivo renal tissues via quantitative histological analysis and shear wave elastography

Ponomarchuk, E., G. Thomas, M. Song, Y.-N. Wang, S. Totten, G. Schade, J. Thiel, M. Bruce, V. Khokhlova, and T. Khokhlova, "Advancing boiling histotripsy dose in ex vivo and in vivo renal tissues via quantitative histological analysis and shear wave elastography," Ultrasound Med. Biol., 50, 1936-1944, doi:10.1016/j.ultrasmedbio.2024.08.022, 2024.

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1 Dec 2024

Objective
In the context of developing boiling histotripsy (BH) as a potential clinical approach for non-invasive mechanical ablation of kidney tumors, the concept of BH dose (BHD) was quantitatively investigated in porcine and canine kidney models in vivo and ex vivo.

Methods
Volumetric lesions were produced in renal tissue using a 1.5-MHz 256-element HIFU-array with various pulsing protocols: pulse duration tp = 1–10 ms, number of pulses per point ppp = 1–15. Two BHD metrics were evaluated: BHD1 = ppp, BHD2 = tp × ppp. Quantitative assessment of lesion completeness was performed by their histological analysis and assignment of damage score to different renal compartments (i.e., cortex, medulla, and sinus). Shear wave elastography (SWE) was used to measure the Young's modulus of renal compartments in vivo vs ex vivo, and before vs after BH treatments.

Results
In vivo tissue required lower BH doses to achieve identical degree of fractionation as compared to ex vivo. Renal cortex (homogeneous, low in collagen) was equal or higher in stiffness than medulla (anisotropic, collagenous), 5.8–12.2 kPa vs 4.7–9.6 kPa, but required lower BH doses to be fully fractionated. Renal sinus (fatty, irregular, with abundant collagenous structures) was significantly softer ex vivo vs in vivo, 4.9–5.1 kPa vs 9.7–15.2 kPa, but was barely damaged in either case with any tested BH protocols. BHD1 was shown to be relevant for planning the treatment of renal cortex (sufficient BHD1 = 5 pulses in vivo and 10 pulses ex vivo), while none of the tested doses resulted in complete fractionation of medulla or sinus. Post-treatment SWE imaging revealed reduction of tissue stiffness ex vivo by 27–58%, increasing with the applied dose, and complete absence of shear waves within in vivo lesions, both indicative of tissue liquefaction.

Conclusion
The results imply that tissue resistance to mechanical fractionation, and hence required BH dose, are not solely determined by tissue stiffness but also depend on its composition and structural arrangement, as well as presence of perfusion. The SWE-derived reduction of tissue stiffness with increasing BH doses correlated with tissue damage score, indicating potential of SWE for post-treatment confirmation of BH lesion completeness.

Histotripsy-induced bactericidal activity correlates to size of cavitation cloud in vitro

Ambekar, P.A., Y.-N. Wang, T.D. Khokhlova, G.P.L. Thomas, P.B. Rosnitskiy, K. Contreras, D.F. Leotta, A.D. Maxwell, M. Bruce, S. Pierson, S. Totten, Y.N. Kumar, J. Thiel, K.T. Chan, W.C. Liles, E.P. Dellinger, A. Adedipe, W.L. Monsky, and T.J. Matula, "Histotripsy-induced bactericidal activity correlates to size of cavitation cloud in vitro," IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 71, 1868-1878, doi:10.1109/TUFFC.2024.3476438, 2024.

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9 Oct 2024

Large abscesses are walled-off collections of pus and bacteria that often do not respond to antibiotic therapy. Standard of care involves percutaneous placement of indwelling catheter(s) for drainage, a long and uncomfortable process with high rehospitalization rates. The long-term goal of this work is to develop therapeutic ultrasound approaches to eradicate bacteria within abscesses as a noninvasive therapeutic alternative. Inertial cavitation induced by short pulses of focused ultrasound (histotripsy) is known to generate lethal mechanical damage in bacteria. Prior studies with Escherichia coli (E. coli) in suspension demonstrated that bactericidal effects increase with increasing peak negative amplitude, treatment time, and duty cycle. The current study investigated correlates of bactericidal activity with histotripsy cavitation cloud size. Histotripsy was applied to E. coli suspensions in 10-mL sample vials at 810 kHz, 1.2 MHz, or 3.25 MHz for 40 min. The cavitation activity in the sample vials was separately observed with high-speed photography. The cavitation cloud area was quantified from those images. A linear relationship was observed between bacterial inactivation and cavitation cloud size ( R2 = 0.98 ), regardless of the acoustic parameters (specifically frequency, pulse duration, and power) used to produce the cloud.

Dynamic mode decomposition based Doppler monitoring of de novo cavitation induced by pulsed HIFU: An in vivo feasibility study

Song, M., O.A. Sapozhnikov, V.A. Khokhlova, H. Son, S. Totten, Y.-N. Wang, and T.D. Khokhlova, "Dynamic mode decomposition based Doppler monitoring of de novo cavitation induced by pulsed HIFU: An in vivo feasibility study," Sci. Rep., 14, doi:10.1038/s41598-024-73787-w, 2024.

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27 Sep 2024

Pulsed high-intensity focused ultrasound (pHIFU) has the capability to induce de novo cavitation bubbles, offering potential applications for enhancing drug delivery and modulating tissue microenvironments. However, imaging and monitoring these cavitation bubbles during the treatment presents a challenge due to their transient nature immediately following pHIFU pulses. A planewave bubble Doppler technique demonstrated its potential, yet this Doppler technique used conventional clutter filter that was originally designed for blood flow imaging. Our recent study introduced a new approach employing dynamic mode decomposition (DMD) to address this in an ex vivo setting. This study demonstrates the feasibility of the application of DMD for in vivo Doppler monitoring of the cavitation bubbles in porcine liver and identifies the candidate monitoring metrics for pHIFU treatment. We propose a fully automated bubble mode identification method using k-means clustering and an image contrast-based algorithm, leading to the generation of DMD-filtered bubble images and corresponding Doppler power maps after each HIFU pulse. These power Doppler maps are then correlated with the extent of tissue damage determined by histological analysis. The results indicate that DMD-enhanced power Doppler map can effectively visualize the bubble distribution with high contrast, and the Doppler power level correlates with the severity of tissue damage by cavitation. Further, the temporal characteristics of the bubble modes, specifically the decay rates derived from DMD, provide information of the bubble dissolution rate, which are correlated with tissue damage level—slower rates imply more severe tissue damage.

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Inventions

Boiling histotripsy methods and systems for uniform volumetric ablation of an object by high-intensity focused ultrasound waves with shocks

Patent #12,157,018

Patent Number: 12,157,018

Vera Khokhlova, Mike Bailey, Wayne Kreider, Oleg Sapozhnikov, Yak-Nam Wang

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Patent

3 Dec 2024

An example method includes generating an acoustic ultrasound wave that is focused at a focal point. The method further includes sequentially directing the focal point upon distinct portions of an object to form respective shock waves at the distinct portions of the object. The method further includes, via the respective shock waves, causing the distinct portions of the object to boil and form respective vapor cavities. The method further includes causing substantially uniform ablation of a region of the object that comprises the distinct portions. The substantially uniform ablation is caused via interaction of the respective shock waves with the respective vapor cavities. An example ablation system and an example non-transitory computer-readable medium, both related to the example method, are also disclosed.

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

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

7 Jul 2020

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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