Kang Kim

UPMC, Pittsburgh, Pennsylvania, United States

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Publications (77)233.17 Total impact

  • Kang Kim · William R Wagner
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    ABSTRACT: With the rapid expansion of biomaterial development and coupled efforts to translate such advances toward the clinic, non-invasive and non-destructive imaging tools to evaluate implants in situ in a timely manner are critically needed. The required multi-level information is comprehensive, including structural, mechanical, and biological changes such as scaffold degradation, mechanical strength, cell infiltration, extracellular matrix formation and vascularization to name a few. With its inherent advantages of non-invasiveness and non-destructiveness, ultrasound imaging can be an ideal tool for both preclinical and clinical uses. In this review, currently available ultrasound imaging technologies that have been applied in vitro and in vivo for tissue engineering and regenerative medicine are discussed and some new emerging ultrasound technologies and multi-modality approaches utilizing ultrasound are introduced.
    No preview · Article · Oct 2015 · Annals of Biomedical Engineering
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    ABSTRACT: Myocardial infarction (MI) causes myocardial necrosis, triggers chronic inflammatory responses, and leads to pathological remodeling. Controlled delivery of a combination of angiogenic and immunoregulatory proteins may be a promising therapeutic approach for MI. We investigated the bioactivity and therapeutic potential of an injectable, heparin-based coacervate co-delivering an angiogenic factor, fibroblast growth factor-2 (FGF2), and an anti-inflammatory cytokine, Interleukin-10 (IL-10) in a spatially and temporally controlled manner. Coacervate delivery of FGF2 and IL-10 preserved their bioactivities on cardiac stromal cell proliferation in vitro. Upon intramyocardial injection into a mouse MI model, echocardiography revealed that FGF2/IL-10 coacervate treated groups showed significantly improved long-term LV contractile function and ameliorated LV dilatation. FGF2/IL-10 coacervate substantially augmented LV myocardial elasticity. Additionally, FGF2/IL-10 coacervate notably enhanced long-term revascularization, especially at the infarct area. In addition, coacervate loaded with 500 ng FGF2 and 500 ng IL-10 significantly reduced LV fibrosis, considerably preserved infarct wall thickness, and markedly inhibited chronic inflammation at the infarct area. These results indicate that FGF2/IL-10 coacervate has notably greater therapeutic potential than coacervate containing only FGF2. Overall, our data suggest therapeutically synergistic effects of FGF-2/IL-10 coacervate, particularly coacervate with FGF2 and 500 ng IL-10, for the treatment of ischemic heart disease.
    Full-text · Article · Sep 2015 · Biomaterials
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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.
    No preview · Article · Apr 2015 · Computer Methods in Applied Mechanics and Engineering
  • Dae Woo Park · Man M. Nguyen · Kang Kim
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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%.
    No preview · Article · Apr 2015 · The Journal of the Acoustical Society of America
  • Jaesok Yu · Man M. Nguyen · Kang Kim
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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.
    No preview · Article · Apr 2015 · The Journal of the Acoustical Society of America
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    ABSTRACT: Multi-modality imaging is beneficial for both preclinical and clinical applications as it enables complementary information from each modality to be obtained in a single procedure. In this paper, we report the design, fabrication, and testing of a novel tri-modal in vivo imaging system to exploit molecular/functional information from fluorescence (FL) and photoacoustic (PA) imaging as well as anatomical information from ultrasound (US) imaging. The same ultrasound transducer was used for both US and PA imaging, bringing the pulsed laser light into a compact probe by fiberoptic bundles. The FL subsystem is independent of the acoustic components but the front end that delivers and collects the light is physically integrated into the same probe. The tri-modal imaging system was implemented to provide each modality image in real time as well as co-registration of the images. The performance of the system was evaluated through phantom and in vivo animal experiments. The results demonstrate that combining the modalities does not significantly compromise the performance of each of the separate US, PA, and FL imaging techniques, while enabling multi-modality registration. The potential applications of this novel approach to multi-modality imaging range from preclinical research to clinical diagnosis, especially in detection/localization and surgical guidance of accessible solid tumors.
    Full-text · Article · Mar 2015 · Review of Scientific Instruments
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    Full-text · Dataset · Feb 2015
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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.
    No preview · Article · Jan 2015 · Ultrasound in Medicine & Biology
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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.
    Full-text · Article · Jan 2015 · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control
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    ABSTRACT: Most pathological processes due to disease, transplantation, or implantation of engineered tissue constructs result in complex changes to tissue. These changes can lead to morphological, compositional, mechanical, and functional differences which can be used for diagnosis, treatment strategies, and progress monitoring. Technological advances in ultrasound imaging including photoacoustic imaging, shear wave elasticity imaging, and ultrasound thermal strain imaging allow the assessment of these changes. In a manner similar to co-registration of positron emission tomography and computed tomography images, co-registration of these disparate images might help to more accurately localize and identify pathological changes to tissue structure and function. This study presents and evaluates the first non-invasive hybrid ultrasound imaging system that incorporates photoacoustic imaging, shear wave elasticity imaging, and ultrasound thermal strain imaging. In co-registered images using a single probe, the tri-modality system successfully detected an indocyanine green dyed gelatin inclusion, a stiff gelatin inclusion, and a rubber inclusion (mimicking lipid-based tissue).
    No preview · Article · Oct 2014
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    ABSTRACT: Ultrasound-targeted microbubble (MB) destruction has been used to deliver nucleic acids to cancer cells for therapeutic effect. Identifying both the location and cavitation activities of the MBs is needed for efficient and effective treatment. In this study, we implemented passive cavitation imaging into a commercially available ultrasound open platform (Verasonics) for a 128-element linear array transducer, centered at 5 MHz, and applied it to an in-vivo mouse tumor model. Cationic lipid MBs were loaded with a transcription factor decoy that suppresses STAT3 signaling and inhibits tumor growth in murine squamous cell carcinomas. During systemic MB infusion, ultrasound pulses (4 or 20 cycles) were delivered with a 1-MHz single-element transducer (0.4–1.4MPa peak pressures). Channel data were offline beamformed, band-pass filtered, subtracted from reference images acquired without MBs, and co-registered with B-mode images. During MB infusion, harmonics and broadband emissions were detected in the tumor with both frequency spectra and cavitation images. For 4-cycle 0.4 MPa pulses, harmonic signals at 5 MHz and broadband signals 3–7 MHz were 23 dB and at least 5 dB greater with MBs than without MBs, respectively. These preliminary results demonstrate the feasibility of in-vivo passive cavitation imaging and could lead to further studies for optimizing US/MB-mediated delivery of nucleic acids to tumors.
    No preview · Article · Oct 2014 · The Journal of the Acoustical Society of America
  • Dae Woo Park · Kang Kim
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    ABSTRACT: Shear wave elasticity imaging (SWEI) has been widely used to assess the elasticity of tissues. However, the shear modulus estimated in SWEI is often less sensitive in some cases, especially to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. This small mechanical contrast can be enhanced if the tissues are compressed, exhibiting mechanical nonlinearity. In this study, we propose a new approach of nonlinear SWEI and evaluate its feasibility through experiments using a tissue mimicking phantom. SWEI was performed while a tissue mimicking phantom was continually deformed over a relatively large dynamic range of strains. A 1.5% agar mixed with 5% gelatin inclusion of a long cylinder (D: 8 mm, hard) embedded in 0.5% agar mixed with 5% gelatin phantom block (soft) was fabricated. The average shear modulus of the inclusion exhibited noticeable nonlinearity after >10% overall applied strain and sharply increased to 40 kPa at 30% overall applied strain. On the other hand, the average shear modulus of the surrounding phantom block increased almost linearly from 4 to 16 kPa over the same applied strain range. The elastic modulus contrast of the inclusion to the surrounding phantom block was increased from 0.40 at 0% overall applied strain to 1.52 at 30% applied strain, which displays detecting the inclusion better.
    No preview · Conference Paper · Sep 2014
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    ABSTRACT: A large portion of near infrared (NIR) laser energy is lost at the skin surfaces by reflection, for example 30% of the incident energy reflects off with incident angle of 20°. Retrieving the reflected light and redirecting it onto the skin surfaces will increase the effective excitation energy, resulting in an increased photoacoustic (PA) signal for the same light source without increasing power. Increased uniformity of light distribution on the skin is also expected due to multiple random light reflection inside a light retrieving and reflection device. In this study, we fabricated a relatively simple, but effective light illumination improvement device, called light catcher, and integrated it into a compact high frequency ultrasound transducer for small animal imaging. Using chicken breast tissues and a mouse cancer model, feasibility of the light catcher for PA imaging was demonstrated. When using the light catcher, PA signal intensity was increased by 33% (0.44 vs. 0.30) and 28% (0.57 vs. 0.41), and corresponding CNR was improved by 22% (2.66 vs. 2.18) and 23% (1.96 vs. 1.52) compared to without the light catcher for in vitro and in vivo study, respectively. This device might allow deep tissue PA imaging with improved CNR using the same laser power.
    No preview · Conference Paper · Sep 2014
  • Man M Nguyen · Xuan Ding · Francois Yu · Kang Kim
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    ABSTRACT: Ultrasound-induced thermal strain imaging (TSI) using separate heating and imaging transducers has been used to successfully identify lipids and water-based tissues in atherosclerosis plaques. However it 1) has a limited field of view due to a narrow heating beam, 2) requires physically aligning heating and imaging beams, and 3) results in a bulky setup that limits in vivo operation. This study proposes and evaluates a new design for heating beams that can be implemented on a linear array imaging transducer with improved heating area and efficiency as compared to previous implementations. The designed heating beams were implemented with a L7-4 linear array transducer connected to a commercial ultrasound platform (Verasonics). The experiment and simulation results showed that the new design resulted in an effective heating area of approximately 1 cm lateral × 1 cm axial and a heating rate of up to 0.44 °C/sec.
    No preview · Conference Paper · Sep 2014
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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.
    Full-text · Article · Jun 2014 · Biomaterials
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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.
    Full-text · Article · May 2014 · ACS Nano
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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.
    No preview · Article · Feb 2014 · Physics in Medicine and Biology
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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.
    No preview · Article · Dec 2013 · IEEE transactions on ultrasonics, ferroelectrics, and frequency control
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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.
    Full-text · Article · Oct 2013 · Biomaterials
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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.
    Full-text · Article · Aug 2013 · Ultrasound in medicine & biology

Publication Stats

859 Citations
233.17 Total Impact Points

Institutions

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