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Stuart Mitchell

Affiliate Senior Engineer






2000-present and while at APL-UW

Characterizing an agar/gelatin phantom for image guided dosing and feeback control of high-intensity focused ultrasound

Dunmire, B., J.C. Kucewicz, S.B. Mitchell, L.A. Crum, and K.M Sekins, "Characterizing an agar/gelatin phantom for image guided dosing and feeback control of high-intensity focused ultrasound," Ultrasound Med. Biol., 39, 300-311, 2013.

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1 Feb 2013

The temperature dependence of an agar/gelatin phantom was evaluated. The purpose was to predict the material property response to high-intensity focused ultrasound (HIFU) for developing ultrasound guided dosing and targeting feedback. Changes in attenuation, sound speed, shear modulus and thermal properties with temperature were examined from 20°C to 70°C for 3 weeks post-manufacture. The attenuation decreased with temperature by a power factor of 0.15. Thermal conductivity, diffusivity and specific heat all increased linearly with temperature for a total change of approximately 16%, 10% and 6%, respectively. Sound speed had a parabolic dependence on temperature similar to that of water. Initially, the shear modulus irreversibly declined with even a slight increase in temperature. Over time, the gel maintained its room temperature shear modulus with moderate heating. A stable phantom was achieved within 2 weeks post-manufacture that possessed quasi-reversible material properties up to nearly 55°C.

Novel high-intensity focused ultrasound clamp — potential adjunct for laparoscopic partial nephrectomy

Harper, J.D., A. Shah, S.B. Mitchell, Y.N. Wang, F. Starr, M.R. Bailey, and L.A. Crum, "Novel high-intensity focused ultrasound clamp — potential adjunct for laparoscopic partial nephrectomy," J. Endourol., 26, 1494-1499, doi:10.1098/end.2012.0107, 2012.

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1 Nov 2012

Partial nephrectomy (PN) can be technically challenging, especially if performed in a minimally invasive manner. Although ultrasound technology has been shown to have therapeutic capabilities, including tissue ablation and hemostasis, it has not gained clinical use in the PN setting. The purpose of this study is to evaluate the ability of a high-intensity ultrasound clamp to create an ablation plane in the kidney providing hemostasis that could potentially aid in laparoscopic PN.
A new instrument was created using a laparoscopic Padron endoscopic exposing retractor. Ultrasound elements were engineered on both sides of the retractor to administer high-intensity ultrasound energy between the two sides of the clamp. This high-intensity focused ultrasound (HIFU) clamp was placed 2 to 2.5 cm from the upper and lower poles of 10 porcine kidneys to evaluate its effectiveness at different levels and duration of energy delivery. PN transection was performed through the distal portion of the clamped margin. Kidneys postintervention and after PN were evaluated and blood loss estimated by weighing gauze placed at the defect. Histologic analysis was performed with hematoxylin and eosin and nicotinamide adenine dinucleotide staining to evaluate for tissue viability and thermal spread.
Gross parenchymal changes were seen with obvious demarcation between treated and untreated tissue. Increased ultrasound exposure time (10 vs 5 and 2 min), even at lower power settings, was more effective in causing destruction and necrosis of tissue. Transmural ablation was achieved in three of four renal units after 10 minutes of exposure with significantly less blood loss (<2 g vs 30-100 g). Nonviable tissue was confirmed histologically. There was minimal thermal spread outside the clamped margin (1.2-3.2 mm).
In this preliminary porcine evaluation, a novel HIFU clamp induced hemostasis and created an ablation plane in the kidney. This technology could serve as a useful adjunct to laparoscopic PN in the future and potentially obviate the need for renal hilar clamping.

Effect of low intensity pulsed ultrasound on mesenchymal stem cells

Ruan, J.L., Y.N. Wang, L.A. Crum, and S.B. Mitchell, "Effect of low intensity pulsed ultrasound on mesenchymal stem cells," J. Acoust. Soc. Am., 129, 2576, doi:10.1121/1.3588505, 2011.

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1 Apr 2011

Low intensity pulsed ultrasound (LIPUS) has been used to accelerate tissue regeneration; however, the biological mechanisms of LIPUS induced regeneration is not completely understood. The aim for this study is to elucidate the mechanical effect generated by US for the stimulation of mesenchymal stem cells (MSCs). MSCs were cultured on flexible cell culture membranes and stimulated by US for 10 min daily with acoustic intensities of 0, 6, 13.5, and 22.5 W/cm2. Cell proliferation and viability were evaluated by direct cell count and Alamar Blue assay. Morphological evaluation was performed and cell-matrix interactions were evaluated. Cell-matrix interaction was analyzed by immunochemical staining of focal adhesion proteins. LIPUS enhanced cell proliferation at higher intensities and there was an increase in cell viability after 4 consecutive days of US treatment. No morphological changes were observed in all treatments. Expression of focal adhesion protein, vinculin, was enhanced after 3 consecutive days of ultrasound treatment. Studies of media agitation did not show any enhancement effect in cell proliferation or focal adhesion protein expression. The results validates that US is able to influence the cell matrix interaction. Application of higher acoustic pressure on cell growth environment can stimulate MSC proliferation and focal adhesion.

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Understanding changes in tissue phantom material properties with temperature

Dunmire, B.L., J.C. Kucewicz, S.B. Mitchell, L.A. Crum, and K.M. Sekins, "Understanding changes in tissue phantom material properties with temperature," J. Acoust. Soc. Am., 129, 2405, doi:10.1121/1.3587832, 2011.

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1 Apr 2011

Phantoms used for high intensity focused ultrasound (HIFU) applications require rigorous evaluation of material properties since, locally, the material experiences extreme changes in temperature and stresses with the HIFU treatment. Here we present the testing of an agar-gelatin phantom intended for both acoustic radiation force imaging (ARFI) and HIFU applications. The phantom shear modulus, speed of sound, attenuation, and thermal properties were all evaluated over the range of room temperature to 80C. With the exception of the thermal properties, all measurements were taken during both heating and cool down. Cavitation threshold and melting point were also tested. The change in material sound speed and thermal properties with temperature were quasireversible and similar to that of water. Material attenuation showed a slight decrease with temperature, but appeared to also be reversible. Shear modulus decreased significantly with temperature, going to near zero. The response was not reversible, returning to only approximately one-third of the starting value. These results demonstrate the complex material response that can occur with HIFU treatment. The results also raise the question of how well the test procedures, and thus results, properly reflect the true HIFU conditions.

Detection of blunt force trauma liver injuries using shear wave elastography

Yu, J., P. Kaczkowski, L. Crum, and S. Mitchell, "Detection of blunt force trauma liver injuries using shear wave elastography," J. Acoust. Soc. Am., 128, 2362-2362, 2010

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1 Oct 2010

Violent impacts, such as vehicle accidents, frequently yield injuries of the liver due to its size and its location in the abdominal cavity. Frequently these injuries are fractures which may lead to life-threatening hemorrhage. Currently, a fast means of non-invasively visualizing areas of injuries in the liver due to blunt force trauma does not exist; hence there is a need to develop better imaging modalities of hepatic injuries to assist in clinical assessments. In this study, we investigate the feasibility of visualizing liver fractures using shear wave elastography.

We hypothesize that there is a shear modulus discontinuity between the two edges of a fracture, and we expect that these discontinuities can be observed from the imaging at the boundary of the split. In testing the hypothesis, we first use optical methods to track and study the displacements and motion trajectories of different regions of a hepatic injury phantom in response to shear wave excitations. Then, following Fink et al. [Proc. IEEE Ultrason. Symp. 1767 (2002)], we implement similar methods with a Verasonics ultrasound system and examine the propagation of shear waves induced by the acoustic radiation force in tissue-mimicking phantoms and ex vivo liver.

Preclinical in vivo evaluation of an extracorporeal HIFU device for ablation of pancreatic tumors

Hwang, J.H., Y.-N. Wang, C. Warren, M.P. Upton, F. Starr, Y. Zhou, and S.B. Mitchell, "Preclinical in vivo evaluation of an extracorporeal HIFU device for ablation of pancreatic tumors," Ultrasound Med. Biol., 35, 967-975, 2009.

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1 Jun 2009

Extracorporeal high-intensity focused ultrasound (HIFU) can be used to ablate tissue noninvasively by delivering focused ultrasound energy from an external source. HIFU for clinical treatment of pancreatic cancer has been reported; however, systematic evaluation of the safety and efficacy of pancreatic ablation with HIFU has not been performed. The objectives of this in vivo study are as follows: (1) assess the safety and feasibility of targeting and ablating pancreatic tissue using the FEP-BY02 HIFU system (Yuande Bio-Medical Engineering, Beijing, China); (2) evaluate a method for estimating in situ acoustic treatment energy in an in vivo setting; and (3) identify the optimal treatment parameters that result in safe and effective ablation of the pancreas.

The pancreata of 12 common swine were treated in vivo. Prior to therapy, blood was drawn for laboratory analysis. Animals were then treated with extracorporeal HIFU at three different acoustic treatment energies (750, 1000 and 1250 J). Endoscopy was performed prior to and immediately following HIFU therapy to assess for gastric injury. Blood was drawn after completion of the treatment and on days 2 and 7 following treatment to assess for biochemical evidence of pancreatitis. Animals were then euthanized 7 d following treatment and a necropsy was performed to assess for unintended injury and to obtain pancreatic tissue for histology to assess efficacy of HIFU ablation. Histologic scoring of pancreatic tissue changes was performed by a pathologist blinded to the treatment energy delivered. The degree of ablation identified on histology correlated with the treatment energy. No collateral tissue damage was seen at treatment energies of 750 and 1000 J. At 1250 J, thermal injury to the abdominal muscles and gastric ulcers were observed. There were no premature deaths, serious illnesses, skin burns or evidence of pancreatitis on biochemical analysis. HIFU treatment of the pancreas is feasible, safe and can be used to ablate tissue noninvasively. A clinical trial in humans examining the use of extracorporeal HIFU for palliation of pain related to pancreatic cancer is planned.

High intensity ultrasound activation of coagulation factors

Mitchell, S.B., N.C. Juaire, and Y.-N. Wang, "High intensity ultrasound activation of coagulation factors," J. Acoust. Soc. Am., 123, 3222, 2008.

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1 May 2008

Although it has been demonstrated that High Intensity Focused Ultrasound (HIFU) can induce vascular cauterization, acoustic hemostasis technology has not been successful in making the transition from proof-of-concept to clinical settings. One reason for this lack of acceptance is the limited understanding of the fundamental mechanisms involved in ultrasound–vessel and ultrasound–blood interactions. The aim of this research was to investigate the hematological and biochemical mechanisms which are influenced by HIFU induced coagulation. HIFU was used to induce coagulation in an in vitro hematological flow system and in animal models. The flow circuit and in vivo arteries were instrumented with flow probes and thermocouples in the treatment region. Physiological parameters were recorded throughout the in vivo experiments. Blood samples were drawn for analysis prior to, during, and immediately following each HIFU treatment. Clotting time, complete blood count, and biochemical analysis were performed immediately and citrated samples were immediately centrifuged and frozen for future analysis. Results indicate that HIFU can change local and systemic levels of thombin/anti-thrombin complex (TAT) and tissue plasminogen activator (tPA), as well as induce changes in activated clotting time (ACT). These results indicate that HIFU can induce coagulation via the coagulation cascades (TAT) and that normal hematological response to thrombus formation is unaffected.

A unique device for controlling electrospinning

Mitchell, S.B., and J.E. Sanders, "A unique device for controlling electrospinning," J. Biomed. Mater. Res. A, 78A, 110-120, doi:10.1002/jbm.a.30673, 2006.

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1 Jul 2006

The purpose of this research was to develop a system for controlled electrospinning of fibro-porous scaffolds for tissue engineering applications and to use this system to assess mesh architecture sensitivity to manufacturing parameters. The intent was to achieve scaffolds with well-controlled fiber diameters and inter-fiber spacing. To accomplish these objectives, a custom, closed-loop controlled, electrospinning system was built. The system was unique in that it had a collection surface that was independent of the electrodes. The system allowed independent manipulation and analysis of a number of manufacturing parameters: distance between the electrodes, distance from the nozzle to the collection surface, applied voltage, temperature of the melt, collection surface dielectric strength, and collection surface area. Morphological analysis of fabricated meshes showed that all test parameters significantly affected fiber diameter and inter-fiber spacing. Further, contrary to what is generally accepted in the electrospinning literature, voltage and temperature (inversely related to viscosity) were not the most significant parameters. Features of the collection surface, including dielectric strength and surface area, were more significant. This dominance is, in part, a reflection of the unique electrospinning system used. The collection surface, which was not connected to either of the electrodes, substantially altered the electric field between the electrodes. Using the developed controlled electrospinning system, thermoplastic polyurethane meshes with fiber diameters ranging from 5 to 18 µm with variability less than 1.8% were made; inter-fiber spacing ranged from 4 to 90 µm with variability less than 20.2%. The system has potential use in biomedical applications where meshes with controlled fiber diameter and inter-fiber spacing are of interest.


Method and apparatus for preparing organs and tissues for laparoscopic surgery

Patent Number: 9,198,635

Larry Crum, Mike Bailey, Peter Kaczkowski, Stuart Mitchell

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1 Dec 2015

High intensity ultrasound (HIU) is used to facilitate surgical procedures, such as a laparoscopic partial nephrectomy, with minimal bleeding. An apparatus is configured to emit HIU from one or more transducers that are attached to a minimally invasive surgical instrument. Such a tool preferably can provide sufficient clamping pressure to collapse blood vessels' walls, so that they will be sealed by the application of the HIU, and by the resulting thermal ablation and tissue cauterization. Such an instrument can provide feedback to the user that the lesion is completely transmural and that blood flow to the region distal of the line of thermal ablation has ceased. Similar instruments having opposed arms can be configured for use in conventional surgical applications as well. Instruments can be implemented with transducers on only one arm, and an ultrasound reflective material disposed on the other arm.

Method and Apparatus for Controlled Electrospinning

Patent Number: 9,085,830

Stuart Mitchell, Joan Sanders

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21 Jul 2015

An electrospinning apparatus and methodology is described that produces medical devices, such as scaffolds that induce the formation of a natural fibrous structure (primarily collagen and elastin) in a tissue-engineered medical device. The apparatus uses collection surfaces designed to manipulate or change the electrostatic field so that the electrospun fibers are arranged in desirable patterns that are similar to or mimic the fibrillar structure of an animal tissue. The manipulation results in fibers that are preferentially oriented in a predefined pattern. In addition, the interfiber space between the fibers and the fiber diameter are consistently within a predefined range. Using these techniques in conjunction with controlling polymer properties enables the production of a scaffold that has the structural and mechanical characteristics similar to the native tissue.

Methods and Apparatus for Blood Vessel Fusion

Record of Invention Number: 45347

Larry Crum, Stuart Mitchell, Robert Rho, Stephen Seslar


17 Aug 2010

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