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Tom Matula

Senior Principal Physicist

Affiliate Assistant Professor, Bioengineering and Affiliate Associate Professor, Electrical Engineering

Email

matula@apl.washington.edu

Phone

206-685-7654

Education

B.S. Physics, California State University at Fresno, 1988

M.S. Physics, Washington State University, 1990

Ph.D. Physics, Washington State University, 1993

Projects

Sclerosing Foams Optimized with Ultrasound Preparation

Sclerotherapy is a procedure to treat varicose veins. uWAMIT researchers have discovered that ultrasound applied to therapeutic liquid solutions creates foams with smaller bubbles and a more uniform size distribution than traditional mechanical agitation methods. This technique may yield safer and more effective foam sclerosis treatments.

8 Jul 2016

Ultrasound Contrast Agents (Microbubbles) in the Microvasculature

High-speed images of oscillating micro-bubbles in small blood vessels are imaged to observe how the bubble oscillations might help induce permeation in the endothelium, allowing drugs to be transported across that barrier.

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23 Jan 2013

High-speed images of oscillating micro-bubbles in small blood vessels are imaged to observe how the bubble oscillations might help induce permeation in the endothelium, allowing drugs to be transported across that barrier.

We excise the mesentery, immerse it in a Krebs solution and place it on a microscope. A flash lamp is used to deliver enough light to obtain good images with 50 nsec exposure times. Microbubbles are perfused along with a saline solution. When a vessel is found containing microbubbles, the experiment is triggered, sending a very short ultrasound pulse (1 MHz) towards the tissue sample. 14 images are collected at pre-determined times (usually every 150 or 300 nsec). Quantification of the images gives us information about vessel deformations, bubble oscillations, and registration of the specific locations that are later used to correlate vessel motion with histological observations of vessel damage.

Videos

PIXUL: PIXelated ULtrasound Speeds Disease Biomarker Search

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26 Apr 2018

Accurate assessment of chromatin modifications can be used to improve detection and treatment of various diseases. Further, accurate assessment of chromatin modifications can have an important role in designing new drug therapies. This novel technology applies miniature ultrasound transducers to shear chromatin in standard 96-well microplates. PIXUL saves researchers hours of sample preparation time and reduces sample degradation.

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

Flow Cytometry Techniques Advance Microbubble Science

Researchers at the Center for Industrial and Medical Ultrasound (CIMU) are measuring the physical properties of ultrasound contrast agents — tiny gas bubbles several microns in diameter used to increase sonogram imaging efficiency in the body. When injected to the general circulation they can act as probes and beacons within the body, and can carry and deploy chemotherapeutic payloads.

CIMU researchers have developed a hybrid instrument that combines an off-the-shelf flow cytometer with an acoustic transducer. The cytometer's laser interrogation counts and measures the bubbles while the acoustic interrogation reveals the bubbles' viscosity and elasticity at megahertz frequencies.

5 Dec 2013

More Videos

Publications

2000-present and while at APL-UW

Treating porcine abscesses with histotripsy: A pilot study

Matula, T.J., Y.-N. Wang, T. Khokhlova, D.F. Leotta, J. Kucewicz, A.A. Brayman, M. Bruce, A.D. Maxwell, B.E. MacConaghy, G. Thomas, V.P. Chernikov, S.V. Buravkov, V.A. Khokhlova, K. Richmond, K. Chan, W. Monsky, "Treating porcine abscesses with histotripsy: A pilot study," Ultrasound Med. Biol., 47, 603-619, doi:10.1016/j.ultrasmedbio.2020.10.011, 2021.

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1 Mar 2021

Infected abscesses are walled-off collections of pus and bacteria. They are a common sequela of complications in the setting of surgery, trauma, systemic infections and other disease states. Current treatment is typically limited to antibiotics with long-term catheter drainage, or surgical washout when inaccessible to percutaneous drainage or unresponsive to initial care efforts. Antibiotic resistance is also a growing concern. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. In particular, short pulses of focused ultrasound (i.e., histotripsy) generate mechanical damage through localized cavitation, representing a potential new paradigm for treating abscesses non-invasively, without the need for long-term catheterization and antibiotics. In this pilot study, boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses developed in a novel porcine model. Ultrasound imaging was used to evaluate abscess maturity for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. Cavitation histotripsy was more successful in reducing the bacterial load while having a smaller treatment volume compared with boiling histotripsy. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy

Li, F.F., and 12 others including T.J. Matula, "Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy," Biomaterials, 256, doi:10.1016/j.biomaterials.2020.120219, 2020.

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1 Oct 2020

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM-1 s-1), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.

Histotripsy treatment of abscesses

Matula, T.J., Y.-N. Wang, T. Khokhlova, D.F. Leotta, J. Kucewicz, A.A. Brayman, M. Bruce, A.D. Maxwell, B.E. MacConaghy, G. Thomas, K. Richmond, K. Chan, and W. Monsky, "Histotripsy treatment of abscesses," in Proc., IEEE International Ultrasonics Symposium, 7-11 September, Las Vegas, NV, doi:10.1109/IUS46767.2020.9251683 (IEEE, 2020).

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7 Sep 2020

Abscesses are walled-off collections of infected fluids containing pus and bacteria. They are often treated with percutaneous drainage in which a drainage catheter may be sutured in place for up to several weeks. Complications such as clogged drains or secondary infections require rehospitalization and wound management. Bacteria are susceptible to mechanical damage, and thus we hypothesize that histotripsy may be a potential new paradigm for treating abscesses noninvasively, without the need for long term catheterization and antibiotics. We developed a porcine animal model that recapitulates some of the features of human abscesses (including size and loculations). Boiling and cavitation histotripsy treatments were applied to subcutaneous and intramuscular abscesses in this porcine model. Ultrasound imaging was used to evaluate abscess maturity, for treatment monitoring and assessment of post-treatment outcomes. Disinfection was quantified by counting bacteria colonies from samples aspirated before and after treatment. Histopathological evaluation of the abscesses was performed to identify changes resulting from histotripsy treatment and potential collateral damage. The results of this pilot study suggest focused ultrasound may lead to a technology for in situ treatment of acoustically accessible abscesses.

More Publications

Inventions

Ultrasound System for Shearing Cellular Material in a Microplate

Patent Number: 10,809,166

Tom Matula, Brian MacConaghy, Adam Maxwell

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Patent

20 Oct 2020

Disclosed embodiments include illustrative piezoelectric element array assemblies, methods of fabricating a piezoelectric element array assembly, and systems and methods for shearing cellular material. Given by way of non-limiting example, an illustrative piezoelectric element array assembly includes at least one piezoelectric element configured to produce ultrasound energy responsive to amplified driving pulses. A lens layer is bonded to the at least one piezoelectric element. The lens layer has a plurality of lenses formed therein that are configured to focus ultrasound energy created by single ones of the at least one piezoelectric element into a plurality of wells of a microplate disposable in ultrasonic communication with the lens layer, wherein more than one of the plurality of lenses overlie single ones of the at least one piezoelectric element.

Methods for Separating, Concentrating, and/or Differentiating Between Cells from a Cell Sample

Patent Number: 10,794,827

Tom Matula, Oleg Sapozhnikov, Brian MacConaghy

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Patent

6 Oct 2020

Embodiments are generally related to differentiating and/or separating portions of a sample that are of interest from the remainder of the sample. Embodiments may be directed towards separating cells of interest from a cell sample. In some embodiments, acoustic impedances of the cells of interest may be modified. For example, the acoustic properties of the cells of interest may be modified by attaching bubbles to the cells of interest. The cell sample may then be subjected to an acoustic wave. The cells of interest may be differentiated and/or separated from the remainder of the sample based on relative displacements and/or volumetric changes experienced by the cells of interest in response thereto. The cells of interest may be separated using a standing wave and sorted into separate channels of a flow cell. Optionally, the cells may be interrogated by a light source and differentiated by signals generated in response thereto.

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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