Kang Kim

UPMC, Pittsburgh, Pennsylvania, United States

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Publications (69)208.33 Total impact

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    ABSTRACT: In efforts to improve detection sensitivity of shear wave elasticity imaging of target tissue lesions with relatively small mechanical contrast to the background tissues, shear wave propagation characteristics in tissues under compression loading have been studied. A finite element hyperelastic tissue model was constructed to characterize the changes of propagating shear wave subject to different mechanical loading and to guide in vitro experiments. The shear wave speed sharply increased in an inclusion from 2.4 m/s to 6.3 m/s while it increased from 2.0 m/s to 4.0 m/s in the background tissue with overall compression loading from 0% to 30%. Increased shear wave reflection at the boundary of the inclusion due to increased mechanical contrast was lowered using a directional filter. In vitro experiments were performed using a soft phantom block (0.5% agar with 5% gelatin) that contains a hard inclusion (1.5% agar with 5% gelatin) of a long cylinder (D: 8 mm). The reconstructed shear modulus of the inclusion exhibited noticeable nonlinearity, in contrast to linear increase of shear modulus in the surrounding phantom. As a result, the elastic modulus contrast of the inclusion to the surrounding phantom was increased from 0.47 to 1.41 at compression from 0% to 30%.
    The Journal of the Acoustical Society of America 04/2015; 137(4):2364-2364. DOI:10.1121/1.4920591 · 1.56 Impact Factor
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    ABSTRACT: In this study, micro-droplets developed for photoacoustic imaging and drug delivery have been evaluated in vitro. Induced by a short laser pulse, perfluoropentane mixed with optical dye was vaporized and expanded up to about 20 times of initial diameter of 3–10 micron, generating strong broadband photoacoustic signals. It was found these vaporized droplets became less stable and prone to rupture to ultrasound pulses. The broadband inertial cavitation signals by a very short ultrasound pulse can provide high spatial resolution in passive cavitation imaging. For feasibility test, passive cavitation imaging algorithms were implemented in a commercial ultrasound open platform with a linear array transducer, centered at 5 MHz. The system was synchronized with a 1 MHz unfocused single element transducer. 700kPa single-cycle excitation ultrasound pulse was induced to a 580 μm inner diameter polyethylene tube containing micro-droplets. The cavitation imaging was performed before and after vaporizing droplets by laser. Broadband emissions of 3–7MHz were observed only with vaporized droplets. These preliminary results show the feasibility of cavitation imaging of vaporized droplets with a short ultrasound excitation pulse for improved spatial resolution and could lead to further in-vivo experiments.
    The Journal of the Acoustical Society of America 04/2015; 137(4):2398-2398. DOI:10.1121/1.4920728 · 1.56 Impact Factor
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    ABSTRACT: An approach for computationally efficient inverse material characterization from partial-field response measurements that combines the Gappy proper orthogonal decomposition (POD) machine learning technique with a physics-based direct inversion strategy is presented and evaluated. Gappy POD is used to derive a data reconstruction tool from a set of potential system response fields that are generated from available a priori information regarding the potential distribution of the unknown material properties. Then, the Gappy POD technique is applied to reconstruct the full spatial distribution of the system response from whatever portion of the response field has been measured with the chosen system testing method. Lastly, a direct inversion strategy is presented that is derived from the equations governing the system response (i.e., physics of the system), which utilizes the full-field response reconstructed by Gappy POD to produce an estimate of the spatial distribution of the unknown material properties. The direct inversion technique is a particularly computationally efficient inversion technique, requiring a cost equivalent to a single numerical analysis. Therefore, the majority of the computational expense of the presented approach is the one-time potential response generation for the Gappy POD technique, which leads to an approach that is substantially computationally efficient overall. Two numerically simulated examples are shown in which the elastic modulus distribution was characterized based on partial-field displacement response measurements, both static and dynamic. The inversion procedure was shown to have the capability to efficiently provide accurate estimates to material property distributions from partial-field response measurements. The direct inversion with Gappy POD response estimation was also shown to be substantially tolerant to noise in comparison to the direct inversion given measured full-field response. Lastly, a physical example regarding elastography of an arterial construct from ultrasound imaging response measurements is shown to validate the practical applicability of the direct inversion approach with Gappy POD response reconstruction.
    Computer Methods in Applied Mechanics and Engineering 04/2015; 286. DOI:10.1016/j.cma.2015.01.001 · 2.63 Impact Factor
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    ABSTRACT: Being multilayered and anisotropic, biological tissues such as cardiac and arterial walls are structurally complex, making the full assessment and understanding of their mechanical behavior challenging. Current standard mechanical testing uses surface markers to track tissue deformations and does not provide deformation data below the surface. In the study described here, we found that combining mechanical testing with 3-D ultrasound speckle tracking could overcome this limitation. Rat myocardium was tested with a biaxial tester and was concurrently scanned with high-frequency ultrasound in three dimensions. The strain energy function was computed from stresses and strains using an iterative non-linear curve-fitting algorithm. Because the strain energy function consists of terms for the base matrix and for embedded fibers, spatially varying fiber orientation was also computed by curve fitting. Using finite-element simulations, we first validated the accuracy of the non-linear curve-fitting algorithm. Next, we compared experimentally measured rat myocardium strain energy function values with those in the literature and found a matching order of magnitude. Finally, we retained samples after the experiments for fiber orientation quantification using histology and found that the results satisfactorily matched those computed in the experiments. We conclude that 3-D ultrasound speckle tracking can be a useful addition to traditional mechanical testing of biological tissues and may provide the benefit of enabling fiber orientation computation. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
    Ultrasound in Medicine & Biology 01/2015; 41(4). DOI:10.1016/j.ultrasmedbio.2014.10.021 · 2.10 Impact Factor
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    ABSTRACT: Thermal strain imaging (TSI) can be used to differentiate between lipid and water-based tissues in atherosclerotic arteries. However, detecting small lipid pools in vivo requires accurate and robust displacement estimation over a wide range of displacement magnitudes. Phase-shift estimators such as Loupas' estimator and time-shift estimators such as normalized cross-correlation (NXcorr) are commonly used to track tissue displacements. However, Loupas' estimator is limited by phase-wrapping and NXcorr performs poorly when the SNR is low. In this paper, we present an adaptive displacement estimation algorithm that combines both Loupas' estimator and NXcorr. We evaluated this algorithm using computer simulations and an ex vivo human tissue sample. Using 1-D simulation studies, we showed that when the displacement magnitude induced by thermal strain was >λ/8 and the electronic system SNR was >25.5 dB, the NXcorr displacement estimate was less biased than the estimate found using Loupas' estimator. On the other hand, when the displacement magnitude was ≤λ/4 and the electronic system SNR was ≤25.5 dB, Loupas' estimator had less variance than NXcorr. We used these findings to design an adaptive displacement estimation algorithm. Computer simulations of TSI showed that the adaptive displacement estimator was less biased than either Loupas' estimator or NXcorr. Strain reconstructed from the adaptive displacement estimates improved the strain SNR by 43.7 to 350% and the spatial accuracy by 1.2 to 23.0% (P < 0.001). An ex vivo human tissue study provided results that were comparable to computer simulations. The results of this study showed that a novel displacement estimation algorithm, which combines two different displacement estimators, yielded improved displacement estimation and resulted in improved strain reconstruction.
    IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 01/2015; 62(1):138-51. DOI:10.1109/TUFFC.2014.006516 · 1.50 Impact Factor
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    ABSTRACT: Degradable tissue scaffolds are implanted to serve a mechanical role while healing processes occur and putatively assume the physiological load as the scaffold degrades. Mechanical failure during this period can be unpredictable as monitoring of structural degradation and mechanical strength changes at the implant site is not readily achieved in vivo, and non-invasively. To address this need, a multi-modality approach using ultrasound shear wave imaging (USWI) and photoacoustic imaging (PAI) for both mechanical and structural assessment in vivo was demonstrated with degradable poly(ester urethane)urea (PEUU) and polydioxanone (PDO) scaffolds. The fibrous scaffolds were fabricated with wet electrospinning, dyed with indocyanine green (ICG) for optical contrast in PAI, and implanted in the abdominal wall of 36 rats. The scaffolds were monitored monthly using USWI and PAI and were extracted at 0, 4, 8 and 12 wk for mechanical and histological assessment. The change in shear modulus of the constructs in vivo obtained by USWI correlated with the change in average Young's modulus of the constructs ex vivo obtained by compression measurements. The PEUU and PDO scaffolds exhibited distinctly different degradation rates and average PAI signal intensity. The distribution of PAI signal intensity also corresponded well to the remaining scaffolds as seen in explant histology. This evidence using a small animal abdominal wall repair model demonstrates that multi-modality imaging of USWI and PAI may allow tissue engineers to noninvasively evaluate concurrent mechanical stiffness and structural changes of tissue constructs in vivo for a variety of applications.
    Biomaterials 06/2014; DOI:10.1016/j.biomaterials.2014.05.088 · 8.31 Impact Factor
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    ABSTRACT: In contrast to short-lived neutrophils, macrophages display persistent presence in the lung of animals after pulmonary exposure to carbon nanotubes. While effective in clearance of bacterial pathogens and injured host cells, the ability of macrophages to "digest" carbonaceous nanoparticles has not been documented. Here, we used chemical, biochemical, cell and animal models and demonstrated oxidative biodegradation of oxidatively functionalized single walled carbon nanotubes via superoxide/NO*-> peroxynitrite driven oxidative pathways of activated macrophages facilitating clearance of nanoparticles from the lung.
    ACS Nano 05/2014; 8(6). DOI:10.1021/nn406484b · 12.03 Impact Factor
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    ABSTRACT: Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ∼3 s and ∼9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.
    Physics in Medicine and Biology 02/2014; 59(4):881-895. DOI:10.1088/0031-9155/59/4/881 · 2.92 Impact Factor
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    ABSTRACT: Ultrasound-induced thermal strain imaging (USTSI) for carotid artery plaque detection requires both high imaging resolution (≪100 μm) and sufficient US-induced heating to elevate the tissue temperature (˜1°C to 3°C within 1 to 3 cardiac cycles) to produce a noticeable change in sound speed in the targeted tissues. Because the optimization of both imaging and heating in a monolithic array design is particularly expensive and inflexible, a new integrated approach is presented which utilizes independent ultrasound arrays to meet the requirements for this particular application. This work demonstrates a new approach in dual-array construction. A 3-D printed manifold was built to support both a high-resolution 20 MHz commercial imaging array and 6 custom heating elements operating in the 3.5 to 4 MHz range. For the application of US-TSI in carotid plaque characterization, the tissue target site is 20 to 30 mm deep, with a typical target volume of 2 mm (elevation) × 8 mm (azimuthal) × 5 mm (depth). The custom heating array performance was fully characterized for two design variants (flat and spherical apertures), and can easily deliver 30 W of total acoustic power to produce intensities greater than 15 W/cm(2) in the tissue target region.
    IEEE transactions on ultrasonics, ferroelectrics, and frequency control 12/2013; 60(12):2645-56. DOI:10.1109/TUFFC.2013.2863 · 1.50 Impact Factor
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    ABSTRACT: The objective of this study was to evaluate the long-term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into "neoarteries" (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues.
    Biomaterials 10/2013; 35(1). DOI:10.1016/j.biomaterials.2013.09.081 · 8.31 Impact Factor
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    ABSTRACT: Mechanical strength is a key design factor in tissue engineering of arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to sacrifice of a large number of animals. We propose an ultrasound-based non-invasive technique for the assessment of the mechanical strength of engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via 2-D phase-sensitive speckle tracking. Young's modulus was then calculated by solving the inverse problem from the distension and the recorded pulse pressure. The stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements indicated an increase in Young's modulus, and histology confirmed the growth of cells and collagen fibrils in the constructs. The results indicate that ultrasound elastography can be used to assess and monitor non-invasively the mechanical properties of arterial constructs.
    Ultrasound in medicine & biology 08/2013; 39(11). DOI:10.1016/j.ultrasmedbio.2013.04.023 · 2.10 Impact Factor
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    ABSTRACT: Large lipid pools in vulnerable plaques, in principle, can be detected using ultrasound-based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. Electrocardiography (ECG) gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time-series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments, using a vessel-mimicking phantom and an excised human atherosclerotic artery, for which the cardiac pulsation is simulated by a pulsatile pump.
    IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control 08/2013; 60(8):1660-1668. DOI:10.1109/TUFFC.2013.2748 · 1.50 Impact Factor
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    ABSTRACT: This study examined the feasibility of in vivo detection of lipids in atherosclerotic plaque (AP) by ultrasound (US) thermal strain imaging (TSI). Intraplaque lipid content is thought to contribute to plaque stability. Lipid exhibits a distinctive physical characteristic of temperature-dependent US speed compared to water-bearing tissues. As tissue temperature changes, US radiofrequency (RF) echoes shift in time of flight which produces an apparent strain (temporal or thermal strain: TS). US heating-imaging pulse sequences and transducers were designed and integrated into commercial US scanners for US-TSI of arterial segments. US-RF data were collected while gradually increasing tissue temperature. Phase-sensitive speckle tracking was applied to reconstruct TS maps co-registered to B-scans. Segments from injured atherosclerotic and uninjured non-atherosclerotic common femoral arteries (CFA) in cholesterol fed New Zealand rabbits, and segments from control normal diet fed rabbits (n=14 total) were scanned in vivo at different time points up to 12 weeks. Lipid-rich atherosclerotic lesions exhibited distinct positive TS (+0.19±0.08%) compared with that in non-atherosclerotic (-0.10±0.13%) and control (-0.09±0.09%) segments (p<0.001). US-TSI enabled serial monitoring of lipids during atherosclerosis development. The co-registered set of morphological and compositional information of US-TSI showed good agreement with histology. US-TSI successfully detected and longitudinally monitored lipid progression in atherosclerotic CFA. US-TSI of relatively superficial arteries may be a modality that could be integrated into a commercial US system for noninvasive lipid detection in AP.
    Journal of the American College of Cardiology 07/2013; 62(19). DOI:10.1016/j.jacc.2013.07.013 · 15.34 Impact Factor
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    ABSTRACT: Thermal strain imaging (TSI) can be used to differentiate lipid and water-based tissues in atherosclerotic arteries. However, detecting small lipid pools in vivo requires accurate and robust estimation of displacement over a wide range of displacement magnitudes. Phase-shift estimators such as Loupas' estimator and time-shift estimators like normalized cross-correlation (NXcorr) are commonly used to track tissue displacements. However, Loupas' algorithm is limited by phase-wrapping and NXcorr performs poorly in low SNR situations. In this paper, we present an adaptive displacement estimation algorithm that showed performance that was superior to either Loupas' estimator or NXcorr alone when the displacement estimates were used to reconstruct thermal strain. We evaluated this algorithm using simulation and phantom studies.
    2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
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    ABSTRACT: An ultrasound elasticity microscope was used to map 3-D strain volume in an ex vivo porcine cornea to illustrate its ability to measure the mechanical properties of this tissue. Mechanical properties of the cornea play an important role in its function and, therefore, also in ophthalmic diseases such as kerataconus and corneal ectasia. The ultrasound elasticity microscope combines a tightly focused high-frequency transducer with confocal scanning to produce high-quality speckle over the entire volume of tissue. This system and the analysis were able to generate volume maps of compressional strain in all three directions for porcine corneal tissue, more information than any previous study has reported. Strain volume maps indicated features of the cornea and mechanical behavior as expected. These results constitute a step toward better understanding of corneal mechanics and better treatment of corneal diseases.
    Ultrasound in medicine & biology 05/2013; 39(8). DOI:10.1016/j.ultrasmedbio.2013.02.465 · 2.10 Impact Factor
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    ABSTRACT: The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice.
    Biomaterials 01/2013; 34(11). DOI:10.1016/j.biomaterials.2013.01.036 · 8.31 Impact Factor
  • Ultrasonics Symposium (IUS), 2013 IEEE International; 01/2013
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    ABSTRACT: Reporter genes may serve as endogenous contrast agents in the field of photoacoustic (PA) molecular imaging (PMI), enabling greater characterization of detailed cellular processes and disease progression. To demonstrate the feasibility of using ferritin as a reporter gene, human melanoma SK-24 (SK-MEL-24) cells were co-transfected with plasmid expressing human heavy chain ferritin (H-FT) and plasmid expressing enhanced green fluorescent protein (pEGFP-C1) using lipofectamine™ 2000. Nontransfected SK-MEL-24 cells served as a negative control. Fluorescent imaging of GFP confirmed transfection and transgene expression in co-transfected cells. To detect iron accumulation due to ferritin overexpression in SK-MEL-24 cells, a focused high-frequency ultrasonic transducer (60 MHz, f/1.5), synchronized to a pulsed laser (fluence < 5 mJ/cm(2) ) was used to scan the PA signal at a wide range NIR wavelengths (850-950 nm). PA signal intensity from H-FT transfected SK-MEL-24 cells was about 5-9 dB higher than nontransfected SK-MEL-24 cells at 850-950 nm. Immunofluorescence and RT-PCR analysis both indicate high levels of ferritin expression in H-FT transfected SK-MEL24 cells, with little ferritin expression in nontransfected SK-MEL-24 cells. In this study, the feasibility of using ferritin as a reporter gene for PMI has been demonstrated in vitro. The use of ferritin as a reporter gene represents a novel concept for PMI using an endogenous contrast agent and may provide various opportunities for molecular imaging and basic science research. © 2012 International Society for Advancement of Cytometry.
    Cytometry Part A 10/2012; 81(10):910-5. DOI:10.1002/cyto.a.22160 · 3.07 Impact Factor

Publication Stats

606 Citations
208.33 Total Impact Points

Institutions

  • 2015
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2008–2015
    • University of Pittsburgh
      • • Department of Medicine
      • • Center for Ultrasound Molecular Imaging and Therapeutics
      Pittsburgh, Pennsylvania, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2005–2013
    • University of Michigan
      • Department of Biomedical Engineering
      Ann Arbor, Michigan, United States
    • Pennsylvania State University
      • Applied Research Laboratory
      University Park, Maryland, United States
  • 2004
    • University of Texas at Austin
      • Department of Biomedical Engineering
      Austin, Texas, United States