Vahid Khalilzad-Sharghi | Emory University (original) (raw)
Papers by Vahid Khalilzad-Sharghi
Magnetic Resonance in Medicine, 2015
Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regener... more Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regeneration and mechanical properties of tissue-engineered cartilage in vivo at different growth stages using MR elastography (MRE). Methods: Three types of scaffolds, including silk, collagen, and gelatin seeded by human mesenchymal stem cells, were implanted subcutaneously in mice and imaged at 9.4T where the shear stiffness and transverse MR relaxation time (T 2 ) were measured for the regenerating constructs for 8 wk. An MRE phase contrast spin echo-based sequence was used for collecting MRE images. At the conclusion of the in vivo study, constructs were excised and transcript levels of cartilagespecific genes were quantitated using reverse-transcription polymerase chain reaction. Results: Tissue-engineered constructs showed a cartilage-like construct with progressive tissue formation characterized by increase in shear stiffness and decrease in T 2 that can be correlated with increased cartilage transcript levels including aggrecan, type II collagen, and cartilage oligomeric matrix protein after 8 wk of in vivo culture. Conclusion: Altogether, the outcome of this research demonstrates the feasibility of MRE and MRI for noninvasive monitoring of engineered cartilage construct's growth after implantation and provides noninvasive biomarkers for regeneration, which may be translated into treatment of tissue defects. Magn Reson Med 000:000-000, 2015. V C 2015 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine, 2015
Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regener... more Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regeneration and mechanical properties of tissue-engineered cartilage in vivo at different growth stages using MR elastography (MRE). Methods: Three types of scaffolds, including silk, collagen, and gelatin seeded by human mesenchymal stem cells, were implanted subcutaneously in mice and imaged at 9.4T where the shear stiffness and transverse MR relaxation time (T 2 ) were measured for the regenerating constructs for 8 wk. An MRE phase contrast spin echo-based sequence was used for collecting MRE images. At the conclusion of the in vivo study, constructs were excised and transcript levels of cartilagespecific genes were quantitated using reverse-transcription polymerase chain reaction. Results: Tissue-engineered constructs showed a cartilage-like construct with progressive tissue formation characterized by increase in shear stiffness and decrease in T 2 that can be correlated with increased cartilage transcript levels including aggrecan, type II collagen, and cartilage oligomeric matrix protein after 8 wk of in vivo culture. Conclusion: Altogether, the outcome of this research demonstrates the feasibility of MRE and MRI for noninvasive monitoring of engineered cartilage construct's growth after implantation and provides noninvasive biomarkers for regeneration, which may be translated into treatment of tissue defects. Magn Reson Med 000:000-000, 2015. V C 2015 Wiley Periodicals, Inc.
Tissue Engineering Part C Methods
The tissue engineering community has been vocal regarding the need for non-invasive instruments t... more The tissue engineering community has been vocal regarding the need for non-invasive instruments to assess the development of tissue-engineered constructs. Medical imaging has helped fulfill this role. However, specimens allocated to a test tube for imaging cannot be tested for a prolonged period or returned to the incubator. Therefore, samples are essentially wasted due to potential contamination and transfer in a less than optimal growth environment. In turn, we present a standalone, miniature, magnetic resonance imaging (MRI)-compatible incubator, termed the e-incubator. This incubator uses a microcontroller (MCU) to automatically sense and regulate physiological conditions for tissue culture, thus allowing for concurrent tissue culture and evaluation. The e-incubator also offers an innovative scheme to study underlying mechanisms related to the structural and functional evolution of tissues. Importantly, it offers a key step towards enabling real-time testing of engineered tissue...
Journal of Visualized Experiments
Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical m... more Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiratio...
Annals of biomedical engineering, Jan 7, 2015
Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation s... more Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation system that, with minimum operator handling, can provide real-time visualization and quantification of cells, tissue constructs, and organs. This type of screening system, capable of operating noninvasively to validate tissue, can overcome current limitations like temperature shock, unsustainable cellular environments, sample contamination, and handling/stress. However, this type of system has been a major challenge, until now. Here, we describe the design, fabrication, and characterization of an innovative, autonomous incubation system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner. Termed the e-incubator (patent pending; application number: 13/953,984), this microcontroller-based system is integrated into an MRI scanner and noninvasively screens cells and tissue cultures in an environment where temperature, pH, and media/gas handling are regulated. The 4-week s...
Journal of Visualized Experiments, 2014
Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical m... more Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.
2008 10th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing, 2008
2008 International Symposium on Telecommunications, 2008
In this paper we will introduce a novel method to design tapered transmission line microstrip fil... more In this paper we will introduce a novel method to design tapered transmission line microstrip filters. The proposed approach is based on the theory of partial reflections. Presuming a desired frequency response characteristic, we obtain the tapered line width variation. In order to validate this method a wide-band band stop tapered microstrip filter was designed, simulated, and fabricated.
Journal of Visualized Experiments, 2012
. Actuator characterization procedure. The gelatin scaffold is enclosed by a 0.5% agarose gel. To... more . Actuator characterization procedure. The gelatin scaffold is enclosed by a 0.5% agarose gel. To characterize the motion being transferred into the sample a white noise is first sent into the system (1a) and the resulting motion is detected using a Laser Doppler Vibrometer (1b). Once the resonance frequency is determined, a continuous sinusoid signal at resonance (2a) is sent to determine the displacement (2b) transferred to the gelatin environment.
Tissue engineering. Part C, Methods, Jan 9, 2014
The tissue engineering community has been vocal regarding the need for noninvasive instruments to... more The tissue engineering community has been vocal regarding the need for noninvasive instruments to assess the development of tissue-engineered constructs. Medical imaging has helped fulfill this role. However, specimens allocated to a test tube for imaging cannot be tested for a prolonged period or returned to the incubator. Therefore, samples are essentially wasted due to potential contamination and transfer in a less than optimal growth environment. In turn, we present a standalone, miniature, magnetic resonance imaging-compatible incubator, termed the e-incubator. This incubator uses a microcontroller unit to automatically sense and regulate physiological conditions for tissue culture, thus allowing for concurrent tissue culture and evaluation. The e-incubator also offers an innovative scheme to study underlying mechanisms related to the structural and functional evolution of tissues. Importantly, it offers a key step toward enabling real-time testing of engineered tissues before ...
Biomaterials, 2015
Interaction of serum proteins and nanoparticles leads to a nanoparticleeprotein complex formation... more Interaction of serum proteins and nanoparticles leads to a nanoparticleeprotein complex formation that defines the rational strategy for a clinically relevant formulation for drug delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer nanomedicine. Given this perspective, we have examined the pattern of human serum protein corona formation with our recently engineered magnetic nanoparticles (MNPs). The alteration in particle size, zeta potential, hemotoxicity, cellular uptake/cancer cells targeting potential, and MRI properties of the MNPs after formation of human serum (HS) protein corona were studied. Our results indicated no significant change in particle size of our MNPs upon incubation with 0.5e50 wt/v% human serum, while zeta potential of MNPs turned negative due to human serum adsorption. When incubated with an increased serum and particle concentration, apolipoprotein E was adsorbed on the surface of MNPs apart from serum albumin and transferrin. However, there was no significant primary or secondary structural alterations observed in serum proteins through Fourier transform infrared spectroscopy, X-ray diffraction, and circular dichroism. Hemolysis assay suggests almost no hemolysis at the tested concentrations (up to 1 mg/mL) for MNPs compared to the sodium dodecyl sulfate (positive control). Additionally, improved internalization and uptake of MNPs by C4-2B and Panc-1 cancer cells were observed upon incubation with human serum (HS). After serum protein adsorption to the surface of MNPs, the close vicinity within T 1 (~1.33e1.73 s) and T 2 (~12.35e13.43 ms) relaxation times suggest our MNPs retained inherent MRI potential even after biomolecular protein adsorption. All these superior clinical parameters potentially enable clinical translation and use of this formulation for next generation nanomedicine for drug delivery, cancer-targeting, imaging and theranostic applications.
Tissue-engineered bone (TEB) analysis in vivo relies heavily on tissue histological and end-point... more Tissue-engineered bone (TEB) analysis in vivo relies heavily on tissue histological and end-point evaluations requiring the sacrifice of animals at specific time points. Due to differences in animal response to implanted tissues, the conventional analytical methods to evaluate TEB can introduce data inconsistencies. Additionally, the conventional methods increase the number of animals required to provide an acceptable statistical power for hypothesis testing. Alternatively, our noninvasive optical imaging allows for the longitudinal analysis of regenerating tissue, where each animal acts as its own control, thus reducing overall animal numbers. In our 6 month feasibility study, TEB, consisting of a silk protein scaffold with or without differentiated mesenchymal stem cells, was implanted in a critical-sized calvarial defect mouse model. Osteogenesis of the TEB was monitored through signal variation, using magnetic resonance imaging (MRI) and near-infrared (NIR) optical imaging with IRDye® 800CW BoneTag TM (800CW BT, a bone-specific marker used to label osteogenically differentiated mesenchymal stem cells and mineralization). Histological endpoint measurements and computed tomography (CT) were used to confirm imaging findings. Anatomical MRI revealed decreased signal intensity, indicating mineralization, in the TEB compared to the control (i.e. silk scaffold only) at various growth stages. NIR optical imaging results demonstrated a signal intensity increase of the TEB compared to control. Interpretation of the imaging results were confirmed by histological analysis. Specifically, haematoxylin and eosin staining revealing de novo bone in TEB showed that 80% of the defect was covered by TEB, while only 40% was covered for the control. Taken together, these results demonstrate the potential of multi-modal non-invasive imaging to visualize and quantify TEB for the assessment of regenerative medicine strategies.
Magnetic Resonance in Medicine, 2015
Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regener... more Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regeneration and mechanical properties of tissue-engineered cartilage in vivo at different growth stages using MR elastography (MRE). Methods: Three types of scaffolds, including silk, collagen, and gelatin seeded by human mesenchymal stem cells, were implanted subcutaneously in mice and imaged at 9.4T where the shear stiffness and transverse MR relaxation time (T 2 ) were measured for the regenerating constructs for 8 wk. An MRE phase contrast spin echo-based sequence was used for collecting MRE images. At the conclusion of the in vivo study, constructs were excised and transcript levels of cartilagespecific genes were quantitated using reverse-transcription polymerase chain reaction. Results: Tissue-engineered constructs showed a cartilage-like construct with progressive tissue formation characterized by increase in shear stiffness and decrease in T 2 that can be correlated with increased cartilage transcript levels including aggrecan, type II collagen, and cartilage oligomeric matrix protein after 8 wk of in vivo culture. Conclusion: Altogether, the outcome of this research demonstrates the feasibility of MRE and MRI for noninvasive monitoring of engineered cartilage construct's growth after implantation and provides noninvasive biomarkers for regeneration, which may be translated into treatment of tissue defects. Magn Reson Med 000:000-000, 2015. V C 2015 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine, 2015
Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regener... more Purpose: The purpose of the present study was to apply noninvasive methods for monitoring regeneration and mechanical properties of tissue-engineered cartilage in vivo at different growth stages using MR elastography (MRE). Methods: Three types of scaffolds, including silk, collagen, and gelatin seeded by human mesenchymal stem cells, were implanted subcutaneously in mice and imaged at 9.4T where the shear stiffness and transverse MR relaxation time (T 2 ) were measured for the regenerating constructs for 8 wk. An MRE phase contrast spin echo-based sequence was used for collecting MRE images. At the conclusion of the in vivo study, constructs were excised and transcript levels of cartilagespecific genes were quantitated using reverse-transcription polymerase chain reaction. Results: Tissue-engineered constructs showed a cartilage-like construct with progressive tissue formation characterized by increase in shear stiffness and decrease in T 2 that can be correlated with increased cartilage transcript levels including aggrecan, type II collagen, and cartilage oligomeric matrix protein after 8 wk of in vivo culture. Conclusion: Altogether, the outcome of this research demonstrates the feasibility of MRE and MRI for noninvasive monitoring of engineered cartilage construct's growth after implantation and provides noninvasive biomarkers for regeneration, which may be translated into treatment of tissue defects. Magn Reson Med 000:000-000, 2015. V C 2015 Wiley Periodicals, Inc.
Tissue Engineering Part C Methods
The tissue engineering community has been vocal regarding the need for non-invasive instruments t... more The tissue engineering community has been vocal regarding the need for non-invasive instruments to assess the development of tissue-engineered constructs. Medical imaging has helped fulfill this role. However, specimens allocated to a test tube for imaging cannot be tested for a prolonged period or returned to the incubator. Therefore, samples are essentially wasted due to potential contamination and transfer in a less than optimal growth environment. In turn, we present a standalone, miniature, magnetic resonance imaging (MRI)-compatible incubator, termed the e-incubator. This incubator uses a microcontroller (MCU) to automatically sense and regulate physiological conditions for tissue culture, thus allowing for concurrent tissue culture and evaluation. The e-incubator also offers an innovative scheme to study underlying mechanisms related to the structural and functional evolution of tissues. Importantly, it offers a key step towards enabling real-time testing of engineered tissue...
Journal of Visualized Experiments
Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical m... more Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiratio...
Annals of biomedical engineering, Jan 7, 2015
Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation s... more Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation system that, with minimum operator handling, can provide real-time visualization and quantification of cells, tissue constructs, and organs. This type of screening system, capable of operating noninvasively to validate tissue, can overcome current limitations like temperature shock, unsustainable cellular environments, sample contamination, and handling/stress. However, this type of system has been a major challenge, until now. Here, we describe the design, fabrication, and characterization of an innovative, autonomous incubation system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner. Termed the e-incubator (patent pending; application number: 13/953,984), this microcontroller-based system is integrated into an MRI scanner and noninvasively screens cells and tissue cultures in an environment where temperature, pH, and media/gas handling are regulated. The 4-week s...
Journal of Visualized Experiments, 2014
Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical m... more Myocarditis is an inflammation of the myocardium, but only ~10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.
2008 10th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing, 2008
2008 International Symposium on Telecommunications, 2008
In this paper we will introduce a novel method to design tapered transmission line microstrip fil... more In this paper we will introduce a novel method to design tapered transmission line microstrip filters. The proposed approach is based on the theory of partial reflections. Presuming a desired frequency response characteristic, we obtain the tapered line width variation. In order to validate this method a wide-band band stop tapered microstrip filter was designed, simulated, and fabricated.
Journal of Visualized Experiments, 2012
. Actuator characterization procedure. The gelatin scaffold is enclosed by a 0.5% agarose gel. To... more . Actuator characterization procedure. The gelatin scaffold is enclosed by a 0.5% agarose gel. To characterize the motion being transferred into the sample a white noise is first sent into the system (1a) and the resulting motion is detected using a Laser Doppler Vibrometer (1b). Once the resonance frequency is determined, a continuous sinusoid signal at resonance (2a) is sent to determine the displacement (2b) transferred to the gelatin environment.
Tissue engineering. Part C, Methods, Jan 9, 2014
The tissue engineering community has been vocal regarding the need for noninvasive instruments to... more The tissue engineering community has been vocal regarding the need for noninvasive instruments to assess the development of tissue-engineered constructs. Medical imaging has helped fulfill this role. However, specimens allocated to a test tube for imaging cannot be tested for a prolonged period or returned to the incubator. Therefore, samples are essentially wasted due to potential contamination and transfer in a less than optimal growth environment. In turn, we present a standalone, miniature, magnetic resonance imaging-compatible incubator, termed the e-incubator. This incubator uses a microcontroller unit to automatically sense and regulate physiological conditions for tissue culture, thus allowing for concurrent tissue culture and evaluation. The e-incubator also offers an innovative scheme to study underlying mechanisms related to the structural and functional evolution of tissues. Importantly, it offers a key step toward enabling real-time testing of engineered tissues before ...
Biomaterials, 2015
Interaction of serum proteins and nanoparticles leads to a nanoparticleeprotein complex formation... more Interaction of serum proteins and nanoparticles leads to a nanoparticleeprotein complex formation that defines the rational strategy for a clinically relevant formulation for drug delivery, hyperthermia, and magnetic resonance imaging (MRI) applications in cancer nanomedicine. Given this perspective, we have examined the pattern of human serum protein corona formation with our recently engineered magnetic nanoparticles (MNPs). The alteration in particle size, zeta potential, hemotoxicity, cellular uptake/cancer cells targeting potential, and MRI properties of the MNPs after formation of human serum (HS) protein corona were studied. Our results indicated no significant change in particle size of our MNPs upon incubation with 0.5e50 wt/v% human serum, while zeta potential of MNPs turned negative due to human serum adsorption. When incubated with an increased serum and particle concentration, apolipoprotein E was adsorbed on the surface of MNPs apart from serum albumin and transferrin. However, there was no significant primary or secondary structural alterations observed in serum proteins through Fourier transform infrared spectroscopy, X-ray diffraction, and circular dichroism. Hemolysis assay suggests almost no hemolysis at the tested concentrations (up to 1 mg/mL) for MNPs compared to the sodium dodecyl sulfate (positive control). Additionally, improved internalization and uptake of MNPs by C4-2B and Panc-1 cancer cells were observed upon incubation with human serum (HS). After serum protein adsorption to the surface of MNPs, the close vicinity within T 1 (~1.33e1.73 s) and T 2 (~12.35e13.43 ms) relaxation times suggest our MNPs retained inherent MRI potential even after biomolecular protein adsorption. All these superior clinical parameters potentially enable clinical translation and use of this formulation for next generation nanomedicine for drug delivery, cancer-targeting, imaging and theranostic applications.
Tissue-engineered bone (TEB) analysis in vivo relies heavily on tissue histological and end-point... more Tissue-engineered bone (TEB) analysis in vivo relies heavily on tissue histological and end-point evaluations requiring the sacrifice of animals at specific time points. Due to differences in animal response to implanted tissues, the conventional analytical methods to evaluate TEB can introduce data inconsistencies. Additionally, the conventional methods increase the number of animals required to provide an acceptable statistical power for hypothesis testing. Alternatively, our noninvasive optical imaging allows for the longitudinal analysis of regenerating tissue, where each animal acts as its own control, thus reducing overall animal numbers. In our 6 month feasibility study, TEB, consisting of a silk protein scaffold with or without differentiated mesenchymal stem cells, was implanted in a critical-sized calvarial defect mouse model. Osteogenesis of the TEB was monitored through signal variation, using magnetic resonance imaging (MRI) and near-infrared (NIR) optical imaging with IRDye® 800CW BoneTag TM (800CW BT, a bone-specific marker used to label osteogenically differentiated mesenchymal stem cells and mineralization). Histological endpoint measurements and computed tomography (CT) were used to confirm imaging findings. Anatomical MRI revealed decreased signal intensity, indicating mineralization, in the TEB compared to the control (i.e. silk scaffold only) at various growth stages. NIR optical imaging results demonstrated a signal intensity increase of the TEB compared to control. Interpretation of the imaging results were confirmed by histological analysis. Specifically, haematoxylin and eosin staining revealing de novo bone in TEB showed that 80% of the defect was covered by TEB, while only 40% was covered for the control. Taken together, these results demonstrate the potential of multi-modal non-invasive imaging to visualize and quantify TEB for the assessment of regenerative medicine strategies.