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In JoVE (1)
- Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth
Other Publications (9)
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Physics in Medicine and Biology
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- Acta Orthopaedica
- Magnetic Resonance Imaging
- Journal of Bioscience and Bioengineering
- Biomaterials
- NMR in Biomedicine
- Journal of Neuroscience Methods
Articles by Shadi F. Othman in JoVE
JoVE Bioengineering
Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth
1Department of Biological Systems Engineering, University of Nebraska-Lincoln, 2Department of Engineering Mechanics, University of Nebraska-Lincoln
The procedure demonstrates the methodology of magnetic resonance elastography for monitoring the engineered outcome of adipose and osteogenic tissue engineered constructs through noninvasive local assessment of the mechanical properties using microscopic magnetic resonance elastography (μMRE).
Other articles by Shadi F. Othman on PubMed
Microscopic Magnetic Resonance Elastography (microMRE)
Magnetic resonance elastography (MRE) was extended to the microscopic scale to image low-frequency acoustic shear waves (typically less than 1 kHz) in soft gels and soft biological tissues with high spatial resolution (34 micromx34 micromx500 microm). Microscopic MRE (microMRE) was applied to agarose gel phantoms, frog oocytes, and tissue-engineered adipogenic and osteogenic constructs. Analysis of the low-amplitude shear wave pattern in the samples allowed the material stiffness and viscous loss properties (complex shear stiffness) to be identified with high spatial resolution. microMRE experiments were conducted at 11.74 T in a 56-mm vertical bore magnet with a 10 mm diameterx75 mm length cylindrical space available for the elastography imaging system. The acoustic signals were generated at 550-585 Hz using a piezoelectric transducer and high capacitive loading amplifier. Shear wave motion was applied in synchrony with the MR pulse sequence. The field of view (FOV) ranged from 4 to 14 mm for a typical slice thickness of 0.5 mm. Increasing the agarose gel concentration resulted in an increase in shear elasticity and shear viscosity. Shear wave motion propagated through the frog oocyte nucleus, enabling the measurement of its shear stiffness, and in vitro shear wave images displayed contrast between adipogenic and osteogenic tissue-engineered constructs. Further development of microMRE should enable its use in characterizing stiffer materials (e.g., polymers, composites, articular cartilage) and assessing with high resolution the mechanical properties of developing tissues.
Magnetic Resonance Microscopy for Monitoring Osteogenesis in Tissue-engineered Construct in Vitro
Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T(1) and T(2)), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.
Ultrasound Accelerated Bone Tissue Engineering Monitored with Magnetic Resonance Microscopy
Tissue engineering has the potential to treat bone loss, but current bone restoration methods, including osteogenesis from mesenchymal stem cells (MSCs), require three to four weeks for bone formation to occur. In this study, we stimulated the formation of engineered bone tissue with low-intensity ultrasound, which has been proven to accelerate bone healing in vivo. One group of engineered bone constructs received ultrasound stimulation 20 minutes per day over a 3-week growth period. We monitored the growth of all the engineered constructs quantitatively and noninvasively using magnetic resonance microscopy (MRM), where the T2 relaxation times of all the constructs were measured, on a weekly basis, using an 11.74 T Bruker spectrometer. Histological and immunocytochemical sections were obtained for all constructs and correlated with the MR results. This study shows that ultrasound can accelerate osteogenesis in vitro for tissue engineered bone, the growth and development of which can be monitored using MRM.
High-resolution/high-contrast MRI of Human Articular Cartilage Lesions
Magnetic resonance microscopy (MRM) is an important experimental tool in the identification of early cartilage lesions.
Error Propagation Model for Microscopic Magnetic Resonance Elastography Shear-wave Images
Microscopic magnetic resonance elastography is a high-resolution method for visualizing shear waves and assessing the biomechanical viscoelastic properties of small biological samples. In this work, we used error propagation to develop a simple analytical model that relates the signal-to-noise ratio of MR magnitude images to the variance in shear-wave maps collected using gradient-echo and spin-echo phase-contrast pulse sequences. Our model predicts results for shear-wave images in phantoms, which match the experimentally observed phase variance within 8%. This model can be used to optimize MR pulse sequences for elastography studies, as well as other phase-difference techniques in MRI.
Monitoring Tissue Engineering Using Magnetic Resonance Imaging
Assessment of tissue regeneration is essential to optimize the stages of tissue engineering (cell proliferation, tissue development and implantation). Optical and X-ray imaging have been used in tissue engineering to provide useful information, but each has limitations: for example, poor depth penetration and radiation damage. Magnetic resonance imaging (MRI) largely overcomes these restrictions, exhibits high resolution (approximately 100 microm) and can be applied both in vitro and in vivo. Recently, MRI has been used in tissue engineering to generate spatial maps of tissue relaxation times (T(1), T(2)), water diffusion coefficients, and the stiffness (shear moduli) of developing engineered tissues. In addition, through the use of paramagnetic and superparamagnetic contrast agents, MRI can quantify cell death, assess inflammation, and visualize cell trafficking and gene expression. After tissue implantation MRI can be used to observe the integration of a tissue implant with the surrounding tissues, and to check for early signs of immune rejection. In this review, we describe and evaluate the growing role of MRI in the assessment of tissue engineered constructs. First, we briefly describe the underlying principles of MRI and the expected changes in relaxation times (T(1), T(2)) and the water diffusion coefficient that are the basis for MR contrast in developing tissues. Next, we describe how MRI can be applied to evaluate the tissue engineering of mesenchymal tissues (bone, cartilage, and fat). Finally, we outline how MRI can be used to monitor tissue structure, composition, and function to improve the entire tissue engineering process.
Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy
We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy.
MR Elastography Monitoring of Tissue-engineered Constructs
The objective of tissue engineering (TE) is to create functional replacements for various tissues; the mechanical properties of these engineered constructs are critical to their function. Several techniques have been developed for the measurement of the mechanical properties of tissues and organs; however, current methods are destructive. The field of TE will benefit immensely if biomechanical models developed by these techniques could be combined with existing imaging modalities to enable noninvasive, dynamic assessment of mechanical properties during tissue growth. Specifically, MR elastography (MRE), which is based on the synchronization of a mechanical actuator with a phase contrast imaging pulse sequence, has the capacity to measure tissue strain generated by sonic cyclic displacement. The captured displacement is presented in shear wave images from which the complex shear moduli can be extracted or simplified by a direct measure, termed the shear stiffness. MRE has been extended to the microscopic scale, combining clinical MRE with high-field magnets, stronger magnetic field gradients and smaller, more sensitive, radiofrequency coils, enabling the interrogation of smaller samples, such as tissue-engineered constructs. The following topics are presented in this article: (i) current mechanical measurement techniques and their limitations in TE; (ii) a description of the MRE system, MRE theory and how it can be applied for the measurement of mechanical properties of tissue-engineered constructs; (iii) a summary of in vitro MRE work for the monitoring of osteogenic and adipogenic tissues originating from human adult mesenchymal stem cells (MSCs); (iv) preliminary in vivo studies of MRE of tissues originating from mouse MSCs implanted subcutaneously in immunodeficient mice with an emphasis on in vivo MRE challenges; (v) future directions to resolve current issues with in vivo MRE in the context of how to improve the future role of MRE in TE. Copyright © 2011 John Wiley & Sons, Ltd.
Microscopic Magnetic Resonance Elastography of Traumatic Brain Injury Model
Traumatic brain injury (TBI) is a major cause of death and disability for which there is no cure. One of the issues inhibiting clinical trial success is the lack of targeting specific patient populations due to inconsistencies between clinical diagnostic tools and underlying pathophysiology. The development of reliable, noninvasive markers of TBI severity and injury mechanisms may better identify these populations, thereby improving clinical trial design. Magnetic resonance elastography (MRE), by assessing tissue mechanical properties, can potentially provide such marker. MRE synchronizes mechanical excitations with a phase contrast imaging pulse sequence to noninvasively register shear wave propagation, from which local values of tissue viscoelastic properties can be deduced. The working hypothesis of this study is that TBI involves a compression of brain tissue large enough to bring the material out of its elastic range, sufficiently altering mechanical properties to generate contrast on MRE measurements. To test this hypothesis, we combined microscopic MRE with brain tissue collected from adult male rats subjected to a controlled cortical impact injury. Measurements were made in different regions of interest (somatosensory cortex, hippocampus, and thalamus), and at different time points following the injury (immediate, 24 h, 7 days, 28 days). Values of stiffness in the somatosensory cortex were found to be 23-32% lower in the injured hemisphere than in the healthy one, when no significant difference was observed in the case of sham brains. A preliminary in vivo experiment is also presented, as well as alternatives to improve the faithfulness of stiffness recovery.
