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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

Development of tough hydrogel phantoms to mimic fibrous tissue for focused ultrasound therapies

Kumar, Y.N., Z. Singh, Y.-N. Wang, G.R. Schade, W. Kreider, M. Bruce, E. Vlaisavljevich, T.D. Khokhlova, and A.D. Maxwell, "Development of tough hydrogel phantoms to mimic fibrous tissue for focused ultrasound therapies," Ultrasound Biol. Med., 48, 1762-1777, doi:10.1016/j.ultrasmedbio.2022.05.002, 2022.

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1 Sep 2022

Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffness of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate. The stiffness was established using shear wave elastography (SWE) and indentometry techniques and was found to be representative of human BPH ex vivo prostate tissue. Different phantom compositions and excised ex vivo BPH tissue samples were treated with a 700-kHz histotripsy transducer at different pulse repetition frequencies. Post-treatment, the hybrid gels and the tissue samples exhibited differential reduction in stiffness as measured by SWE. On B-mode ultrasound, partially treated areas were present as hyperechoic zones and fully liquified areas as hypoechoic zones. Phase contrast microscopy of the gel samples revealed liquefaction in regions consistent with the target lesion dimensions and correlated to findings identified in tissue samples via histology. The dose required to achieve liquefaction in the hybrid gel was similar to what has been observed in ex vivo tissue and greater than that of agarose of comparable or higher Young's modulus by a factor >10. These results indicate that the developed hydrogels closely mimic elasticities found in BPH prostate ex vivo tissue and have a similar response to histotripsy treatment, thus making them a useful cost-effective alternative for developing and evaluating different treatment protocols.

Non-Invasive monitoring of increased fibrotic tissue and hyaluronan deposition in the tumor microenvironment in the advanced stages of pancreatic ductal adenocarcinoma

Vohra, R., Y.-N. Wang, H. Son, S. Totten, A. Arora, A. Maxwell, and D. Lee, "Non-Invasive monitoring of increased fibrotic tissue and hyaluronan deposition in the tumor microenvironment in the advanced stages of pancreatic ductal adenocarcinoma," Cancers, 14, doi:10.3390/cancers14040999, 2022.

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16 Feb 2022

Pancreatic ductal adenocarcinomas are characterized by a complex and robust tumor microenvironment (TME) consisting of fibrotic tissue, excessive levels of hyaluronan (HA), and immune cells. We utilized quantitative multi-parametric magnetic resonance imaging (mp-MRI) methods at 14 Tesla in a genetically engineered KPC (KrasLSL-G12D/+, Trp53LSL-R172H/+, Cre) mouse model to assess the complex TME in advanced stages of tumor development. The whole tumor, excluding cystic areas, was selected as the region of interest for data analysis and subsequent statistical analysis. Pearson correlation was used for statistical inference. There was a significant correlation between tumor volume and T2 (r = –0.66), magnetization transfer ratio (MTR) (r = 0.60), apparent diffusion coefficient (ADC) (r = 0.48), and Glycosaminoglycan-chemical exchange saturation transfer (GagCEST) (r = 0.51). A subset of mice was randomly selected for histological analysis. There were positive correlations between tumor volume and fibrosis (0.92), and HA (r = 0.76); GagCEST and HA (r = 0.81); and MTR and CD31 (r = 0.48). We found a negative correlation between ADC low-b (perfusion) and Ki67 (r = –0.82). Strong correlations between mp-MRI and histology results suggest that mp-MRI can be used as a non-invasive tool to monitor the tumor microenvironment.

The compressive, shear, biochemical, and histological characteristics of diabetic and non-diabetic plantar skin are minimally different

Brady, L., S. Pai, J.M. Iaquinto, Y.-N. Wang, and W.R. Ledoux, "The compressive, shear, biochemical, and histological characteristics of diabetic and non-diabetic plantar skin are minimally different," J. Biomech., 129, doi:10.1016/j.jbiomech.2021.110797, 2021.

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2 Dec 2021

Diabetes is associated with lower limb co-morbidities, including ulceration and subsequent amputation. As a systemic disease, diabetes affects the microstructure of soft tissues, and material microstructural changes are known to affect the macroscale mechanics. However, the associations between diabetes-related disruptions to essential microstructural components and mechanical changes in plantar skin with diabetes has not been thoroughly characterized. Plantar skin specimens were collected from four diabetic and eight non-diabetic donors at six plantar locations (hallux; first, third, and fifth metatarsals; lateral midfoot; calcaneus) from matched pairs. Mechanical testing was performed on fresh frozen specimens from one foot, and histomorphological measurement and biochemical quantification were performed on specimens from the other foot. Mechanical (compressive and shear moduli and viscoelastic slopes) and biochemical/histological (total quantity of collagen and elastin; dermal and epidermal thickness) parameters were correlated using linear mixed effects regression. There were no significant differences by disease state. Skin thicknesses were positively correlated with initial compression modulus and all three shear moduli. The final compressive modulus was significantly lower at the third metatarsal than the fifth metatarsal, lateral midfoot, and calcaneus, while the final shear modulus was significantly higher at the calcaneus than at the hallux, first, and third metatarsals. Epidermal thickness was significantly higher at the calcaneus compared to all other locations. While differences were not significant by disease state, the strong differences by locations and significant but weak correlations between skin thickness and mechanics can inform future research to understand the mechanism of ulcer formation in the diabetic foot.

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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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