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Yak-Nam Wang

Senior Engineer

Email

ynwang@apl.washington.edu

Phone

206-616-6673

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.

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23 Mar 2017

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

Evaluation of pancreatic tumor development in KPC mice using multi-parametric MRI

Vohra, R., J. Park, Y.-N. Wang, K. Gravelle, S. Whang, J.-H. Hwang, and D. Lee, "Evaluation of pancreatic tumor development in KPC mice using multi-parametric MRI," Cancer Imaging, 18, doi:10.1186/s40644-018-0172-6, 2018.

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8 Nov 2018


Background
Pancreatic ductal adenocarcinoma (PDA) is a fatal disease with very poor prognosis. Development of sensitive and noninvasive methods to monitor tumor progression in PDA is a critical and unmet need. Magnetic resonance imaging (MRI) can noninvasively provide information regarding underlying pathophysiological processes such as necrosis, inflammatory changes and fibrotic tissue deposition.

Methods
A genetically engineered KPC mouse model that recapitulates human PDA was used to characterize disease progression. MR measures of T1 and T2 relaxation times, magnetization transfer ratio (MTR), diffusion and chemical exchange saturation transfer were compared in two separate phases i.e. slow and rapid growth phase of tumor. Fibrotic tissue accumulation was assessed histologically using Masson’s trichrome staining. Pearson correlation coefficient (r) was computed to assess the relationship between the fibrotic tissue accumulation and different MR parameters.

Results
There was a negative correlation between amide proton transfer signal intensity and tumor volume (r = – 0.63, p = 0.003) in the slow growth phase of the tumor development. In the terminal stage of rapid growth phase of the tumor development MTR was strongly correlated with tumor volume (r = 0.62, p = 0.008). Finally, MTR was significantly correlated with % fibrosis (r = 0.87; p < 0.01), followed by moderate correlation between tumor volume (r = 0.42); T1 (r = − 0.61), T2 (r = − 0.61) and accumulation of fibrotic tissue.

Conclusions
Here we demonstrated, using multi-parametric MRI (mp-MRI), that MRI parameters changed with tumor progression in a mouse model of PDA. Use of mp-MRI may have the potential to monitor the dynamic changes of tumor microenvironment with increase in tumor size in the transgenic KPC mouse model of pancreatic tumor.

Inactivation of planktonic Escherichia coli by focused 1-MHz ultrasound pulses with shocks: Efficacy and kinetics upon volume scale-up

Brayman, A.A., B.E. MacConaghy, Y.-N. Wang, K.T. Chan, W.L. Monsky, V.P. Chernikov, S.V. Buravkov, V.A. Khokhlova, and T.J. Matula, "Inactivation of planktonic Escherichia coli by focused 1-MHz ultrasound pulses with shocks: Efficacy and kinetics upon volume scale-up," Ultrasound Med. Biol., 44, 1996-2008, doi:10.1016/j.ultrasmedbio.2018.05.010, 2018.

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1 Sep 2018

This study addresses inactivation of E. coli in either 5- or 10-mL volumes, which were 50- to 100-fold greater than used in an earlier study (Brayman et al. 2017). Cells were treated with 1-MHz pulsed high-intensity focused ultrasound (10 cycles, 2-kHz repetition frequency, +65/–12.8 MPa focal pressures). The surviving fraction was assessed by coliform assay, and inactivation demonstrated curvilinear kinetics. The reduction of surviving fraction to 50% required 2.5 or 6 min in 5- or 10-mL samples, respectively. Exposure of 5 mL for 20 min reduced the surviving fraction to ~1%; a similar exposure of 10-mL samples reduced the surviving fraction to ~10%. Surviving cells from 5-min exposures appeared normal under light microscopy, with minimal debris; after 20 min, debris dominated. Transmission electron microscopy images of insonated samples showed some undamaged cells, a few damaged but largely intact cells and comminuted debris. Cellular damage associated with substantive but incomplete levels of inactivation can be variable, ranging from membrane holes tens of nanometers in diameter to nearly complete comminution.

Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: A pre-clinical study in a genetic model of pancreatic cancer

Farr, N., and 12 others inlcuding Y.-N. Wang and F. Starr, "Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: A pre-clinical study in a genetic model of pancreatic cancer," Int. J. Hypertherm., 34, 284-291, doi:10.1080/02656736.2017.1336675, 2018.

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1 Mar 2018

The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer.

Localized hyperthermia was successfully applied and monitored with a clinical MR-HIFU system. The mild hyperthermia heating algorithm administered by the MR-HIFU system resulted in homogenous heating within the region of interest. MR-HIFU, in combination with LTSL-Dox, resulted in a 23-fold increase in the localised drug concentration and nuclear uptake of doxorubicin within the tumour tissue of KPC mice compared to LTSL-Dox alone. Hyperthermia, in combination with free Dox, resulted in a 2-fold increase compared to Dox alone.

This study demonstrates that HIFU-induced hyperthermia in combination with LTSL-Dox can be a non-invasive and effective method in enhancing the localised delivery and penetration of doxorubicin into pancreatic tumours.

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Inventions

MRI-Guided Lithotripsy of Urinary Tract Stones

Record of Invention Number: 47984

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

Disclosure

23 Feb 2017

Methods of Soft Tissue Emulsification using a Mechanism of Ultrasonic Atomization Inside Gas or Vapor Cavities and Associated Systems and Devices

Patent Number: 9,498,651

Oleg Sapozhnikov, Mike Bailey, Larry Crum, Vera Khokhlova, Yak-Nam Wang

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Patent

22 Nov 2016

The present technology is directed to methods of soft tissue emulsification using a mechanism of ultrasonic atomization inside gas or vapor cavities, and associated systems and devices. In several embodiments, for example, a method of non-invasively treating tissue includes pulsing ultrasound energy from the ultrasound source toward the target site in tissue. The ultrasound source is configured to emit high intensity focused ultrasound (HIFU) waves. The target site comprises a pressure-release interface of a gas or vapor cavity located within the tissue. The method continues by generating shock waves in the tissue to induce a lesion in the tissue at the target site. The method additionally includes characterizing the lesion based on a degree of at least one of a mechanical or thermal ablation of the tissue.

Noninvasive Disintegration of Peyronie's Plaque with Focused Ultrasound

Record of Invention Number: 47233

Hunter Wessells, Mike Bailey, Mahri Haider, Tatiana Khokhlova, Frank Lee, Adam Maxwell, George Schade, Yak-Nam Wang

Disclosure

23 Feb 2015

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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