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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

Ultrastructural analysis of volumetric histotripsy bio-effects in large human hematomas

Ponomarchuk, E.M., and 12 others including Y.-N. Wang, O.A. Sapozhnikov, and V.A. Khokhlova, "Ultrastructural analysis of volumetric histotripsy bio-effects in large human hematomas," Ultrasound Biol. Med., 47, 2608-2621, doi:10.1016/j.ultrasmedbio.2021.05.002, 2021.

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1 Sep 2021

Large-volume soft tissue hematomas are a serious clinical problem, which, if untreated, can have severe consequences. Current treatments are associated with significant pain and discomfort. It has been reported that in an in vitro bovine hematoma model, pulsed high-intensity focused ultrasound (HIFU) ablation, termed histotripsy, can be used to rapidly and non-invasively liquefy the hematoma through localized bubble activity, enabling fine-needle aspiration. The goals of this study were to evaluate the efficiency and speed of volumetric histotripsy liquefaction using a large in vitro human hematoma model. Large human hematoma phantoms (85 cc) were formed by recalcifying blood anticoagulated with citrate phosphate dextrose/saline–adenine–glucose–mannitol solution. Typical boiling histotripsy pulses (10 or 2 ms) or hybrid histotripsy pulses using higher-amplitude and shorter pulses (0.4 ms) were delivered at 1% duty cycle while continuously translating the HIFU focus location. Histotripsy exposures were performed under ultrasound guidance with a 1.5-MHz transducer (8-cm aperture, F# = 0.75). The volume of liquefied lesions was determined by ultrasound imaging and gross inspection. Untreated hematoma samples and samples of the liquefied lesions aspirated using a fine needle were analyzed cytologically and ultrastructurally with scanning electron microscopy. All exposures resulted in uniform liquid-filled voids with sharp edges; liquefaction speed was higher for exposures with shorter pulses and higher shock amplitudes at the focus (up to 0.32, 0.68 and 2.62 mL/min for 10-, 2- and 0.4-ms pulses, respectively). Cytological and ultrastructural observations revealed completely homogenized blood cells and fibrin fragments in the lysate. Most of the fibrin fragments were less than 20 μm in length, but a number of fragments were up to 150 μm. The lysate with residual debris of that size would potentially be amenable to fine-needle aspiration without risk for needle clogging in clinical implementation.

Characterization and ex vivo evaluation of an extracorporeal high-intensity focused ultrasound (HIFU) system

Zhou, Y.F., B.W. Cunitz, B. Dunmire, Y.-N. Wang, S.G. Karl, C. Warren, S. Mitchell, and J.H. Hwang, "Characterization and ex vivo evaluation of an extracorporeal high-intensity focused ultrasound (HIFU) system," J. Appl. Clin. Med. Phys., EOR, doi:10.1002/acm2.13074, 2021.

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4 Aug 2021

High-intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required.

The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo.

Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre- or post-focal peaks (≤–12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of –11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20-mm target, which suggests the well-controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750–1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling.

Our characterization and ex vivo evaluation protocol met the IDE requirement. The in-situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.

Factors affecting tissue cavitation during burst wave lithotripsy

Maxwell, A.D., C. Hunter, B.W. Cunitz, W. Kreider, S. Totten, and Y.-N. Wang, "Factors affecting tissue cavitation during burst wave lithotripsy," Ultrasound Med. Biol., 47, 2286-2295, doi:10.1016/j.ultrasmedbio.2021.04.021, 2021.

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1 Aug 2021

Burst wave lithotripsy (BWL) is a technology under clinical investigation for non-invasive fragmentation of urinary stones. Under certain ranges of ultrasound exposure parameters, this technology can cause cavitation in tissue leading to renal injury. This study sought to measure the focal pressure amplitude needed to cause cavitation in vivo and determine its consistency in native tissue, in an implanted stone model and under different exposure parameters. The kidneys of eight pigs were exposed to transcutaneous BWL ultrasound pulses. In each kidney, two locations were targeted: the renal sinus and the kidney parenchyma. Each was exposed for 5 min at a set pressure level and parameters, and cavitation was detected using an active cavitation imaging method based on power Doppler ultrasound. The threshold was determined by incrementing the pressure amplitude up or down after each 5-min interval until cavitation occurred/subsided. The pressure thresholds were remeasured postsurgery, targeting an implanted stone or collecting space (in sham). The presence of a stone or sham surgery did not significantly impact the threshold for tissue cavitation. Targeting parenchyma instead of kidney collecting space and lowering the ultrasound pulse repetition frequency both resulted in an increased pressure threshold for cavitation.

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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

7 Jul 2020

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

Audio Feedback for Improving the Accuracy of BWL Targeting

Record of Invention Number: 48254

Mike Bailey, Bryan Cunitz, Barbrina Dunmire, Christopher Hunter, Wayne Kreider, Adam Maxwell, Yak-Nam Wang

Disclosure

25 Jan 2018

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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