Feasibility of noninvasive evaluation of biophysical properties of tissue-engineered cartilage by using quantitative MRI

Miyata, Shogo; Numano, Tomokazu; Homma, Kazuhiro; Tateishi, Tetsuya; Ushida, Takashi

doi:10.1016/j.jbiomech.2007.02.002

Cited by 40 publications

(40 citation statements)

References 25 publications

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“…18,31 In addition, Miyata et al showed a strong correlation for T 1 and ADC, but not for T 2 , with the equilibrium Young's modulus of engineered cartilage using articular chondrocytes seeded in an agarose gel scaffold. 32 Similarly, Neves et al found that the effects of perfusion and nutrient diffusion on cell growth and distribution and matrix production in meniscal cartilage constructs could be assessed using MRI and spectroscopy. 13,17 Other investigators have used MRI to estimate the matrix fixed charge density of engineered cartilage using gadolinium exclusion.…”

Section: Discussionmentioning

confidence: 99%

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Hong

et al. 2010

Tissue Engineering Part C: Methods

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The goal of the present investigation was to test whether quantitative magnetization transfer imaging can be used as a noninvasive evaluation method for engineered cartilage. In this work, we used magnetic resonance imaging (MRI) to monitor the chondrogenesis of stem-cell-based engineered tissue over a 3-week period by measuring on a pixel-by-pixel basis the relaxation times (T 1 and T 2 ), the apparent diffusion coefficient, and the magnetization transfer parameters: bound proton fraction and cross-relaxation rate (k). Tissue-engineered constructs for generating cartilage were created by seeding mesenchymal stem cells in a gelatin sponge. Every 7 days, tissue samples were analyzed using MRI, histological, and biochemical methods. The MRI measurements were verified by histological analysis, and the imaging data were correlated with biochemical analysis of the developing cartilage matrix for glycosaminoglycan content. The MRI analysis for bound proton fraction and k showed a statistically significant increase that was correlated with the increase of glycosaminoglycan (R ¼ 0.96 and 0.87, respectively, p < 0.05), whereas T 1 , T 2 , and apparent diffusion coefficient results did not show any significant changes over the 3-week measurement period.

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Section: Discussionmentioning

confidence: 99%

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Hong

et al. 2010

Tissue Engineering Part C: Methods

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“…40 Yin et al, 89 for example, found that the relaxation times and diffusion coefficient (T 1 , T 1rho , ADC, and T 2 ) all decreased (T 1 by 18%, T 2 by 42%, and ADC by 26%) in a 4-week study of chondrocyte pellets (a scaffold-free tissue-engineering model). However, in a 4-week study of chondrocytes grown in an agarose gel, Miyata et al, 35 found that while the longitudinal relaxation times (T 1 ) and apparent diffusion coefficient (ADC) decreased, the transverse relaxation time (T 2 ) increased. These results demonstrate that MRI analysis is able to detect unexpected changes in the tissue microenvironment through measurements, in this case, of the T 2 relaxation times.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…MRS and imaging are wellestablished techniques that have been used to probe the structure and dynamics of biochemical changes in engineered tissues. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] MR elastography, while relatively new, is rapidly being employed to assess the mechanical properties of engineered tissues. 30,43 Using MR spectroscopy, imaging, and elastography together, it is possible to create three-dimensional (3D) maps of chemical shifts, relaxation times, diffusion coefficient, spectral couplings, and tissue stiffness.…”

mentioning

confidence: 99%

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Kotecha

Klatt

Magin

2013

Tissue Engineering Part B: Reviews

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A key technical challenge in cartilage tissue engineering is the development of a noninvasive method for monitoring the composition, structure, and function of the tissue at different growth stages. Due to its noninvasive, three-dimensional imaging capabilities and the breadth of available contrast mechanisms, magnetic resonance imaging (MRI) techniques can be expected to play a leading role in assessing engineered cartilage. In this review, we describe the new MR-based tools (spectroscopy, imaging, and elastography) that can provide quantitative biomarkers for cartilage tissue development both in vitro and in vivo. Magnetic resonance spectroscopy can identify the changing molecular structure and alternations in the conformation of major macromolecules (collagen and proteoglycans) using parameters such as chemical shift, relaxation rates, and magnetic spin couplings. MRI provides high-resolution images whose contrast reflects developing tissue microstructure and porosity through changes in local relaxation times and the apparent diffusion coefficient. Magnetic resonance elastography uses low-frequency mechanical vibrations in conjunction with MRI to measure soft tissue mechanical properties (shear modulus and viscosity). When combined, these three techniques provide a noninvasive, multiscale window for characterizing cartilage tissue growth at all stages of tissue development, from the initial cell seeding of scaffolds to the development of the extracellular matrix during construct incubation, and finally, to the postimplantation assessment of tissue integration in animals and patients.

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“…The application of magnetic resonance imaging (MRI) for visualizing cartilage clinically has been well established, 1,2 while more recently, approaches have been developed to monitor cartilage matrix components in human subjects [3][4][5][6][7][8] and in engineered cartilage constructs. [9][10][11][12][13][14] These latter techniques may be particularly useful for tailoring therapeutic interventions after implantation into a defect.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Assessment of Glycosaminoglycan Production in Injectable Tissue-Engineered Cartilage Constructs Using Magnetic Resonance Imaging

Ramaswamy

Uluer²,

Leen³

et al. 2008

Tissue Engineering Part C: Methods

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The glycosaminoglycan (GAG) content of engineered cartilage is a determinant of biochemical and mechanical quality. The ability to measure the degree to which GAG content is maintained or increases in an implant is therefore of importance in cartilage repair procedures. The gadolinium exclusion magnetic resonance imaging (MRI) method for estimating matrix fixed charge density (FCD) is ideally suited to this. One promising approach to cartilage repair is use of seeded injectable hydrogels. Accordingly, we assess the reliability of measuring GAG content in such a system ex vivo using MRI. Samples of the photopolymerizable hydrogel, poly(ethylene oxide) diacrylate, were seeded with bovine chondrocytes (*2.4 million cells/sample). The FCD of the constructs was determined using MRI after 9, 16, 29, 36, 43, and 50 days of incubation. Values were correlated with the results of biochemical determination of GAG from the same samples. FCD and GAG were found to be statistically significantly correlated (R 2 = 0.91, p < 0.01). We conclude that MRI-derived FCD measurements of FCD in injectable hydrogels reflect tissue GAG content and that this methodology therefore has potential for in vivo monitoring of such constructs.

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Feasibility of noninvasive evaluation of biophysical properties of tissue-engineered cartilage by using quantitative MRI

Cited by 40 publications

References 25 publications

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Noninvasive Assessment of Glycosaminoglycan Production in Injectable Tissue-Engineered Cartilage Constructs Using Magnetic Resonance Imaging

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