Magnetization transfer imaging provides a quantitative measure of chondrogenic differentiation and tissue development.

Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, USA.
Tissue Engineering Part C Methods (Impact Factor: 4.64). 04/2010; 16(6):1407-15. DOI: 10.1089/ten.TEC.2009.0777
Source: PubMed

ABSTRACT 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 (T₁ and T₂), 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 = 0.96 and 0.87, respectively, p < 0.05), whereas T₁, T₂, and apparent diffusion coefficient results did not show any significant changes over the 3-week measurement period.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Magnetization transfer magnetic resonance imaging measurements were performed in three pancreatic ductal adenocarcinoma mouse xenograft models. For each of 28 pancreatic ductal adenocarcinoma xenografts, MT ratios (MTRs) were calculated and compared to histologic fibrosis levels from reference standard trichrome staining. MTR was found to be significantly higher in tumors grown using BxPC-3 cell line (39.4 ± 5.1, mean ± SD) compared to the MTR for the tumors grown from Panc-1 (32.4 ± 2.8) and Capan-1 (27.3 ± 2.9) cell lines (P < 0.05 for each comparison). Histologic measurements showed a similar trend with BxPC-3 tumors demonstrating significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.48 ± 2.59) when compared to Panc-1 (3.54 ± 2.18) and Capan-1 (2.07 ± 1.60) tumors. MTR measurements were well correlated to quantitative fibrosis levels (r = 0.69, P = 0.01). Results indicated that MTR measurements offer the potential to serve as a valuable in vivo biomarker of desmoplasia in pancreatic ductal adenocarcinoma. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 12/2011; 68(4):1291-7. · 3.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A key technical challenge in cartilage tissue engineering is the development of a non-invasive 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 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 (MRS) can identify changing molecular structure and alternations in the conformation of major macromolecules (collagen and proteoglycans) using parameters such as chemical shift, relaxation rates, magnetic spin couplings. Magnetic resonance imaging 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 (MRE) 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, multi-scale 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 post-implantation assessment of tissue integration in animals and patients.
    Tissue Engineering Part B Reviews 04/2013; · 4.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We studied the tissue growth dynamics of tissue-engineered cartilage at an early growth stage after cell seeding for four weeks using sodium triple-quantum coherence NMR spectroscopy. The following tissue-engineering constructs were studied: 1) bovine chondrocytes cultured in alginate beads; 2) bovine chondrocytes cultured as pellets (scaffold-free chondrocyte pellets); and 3) human marrow stromal cells (HMSCs) seeded in collagen/chitosan based biomimetic scaffolds. We found that the sodium triple-quantum coherence spectroscopy could differentiate between different tissue-engineered constructs and native tissues based on the fast and slow components of relaxation rate as well as on the average quadrupolar coupling. Both fast (T(f) ) and slow (T(s) ) relaxation times were found to be longer in chondrocyte pellets and biomimetic scaffolds compared to chondrocytes suspended in alginate beads and human articular cartilage tissues. In all cases, it was found that relaxation rates and motion of sodium ions measured from correlation times were dependent on the amount of macromolecules, high cell density and anisotropy of the cartilage tissue-engineered constructs. Average quadrupolar couplings were found to be lower in the engineered tissue compared to native tissue, presumably due to the lack of order in collagen accumulated in the engineered tissue. These results support the use of sodium triple-quantum coherence spectroscopy as a tool to investigate anisotropy and growth dynamics of cartilage tissue-engineered constructs in a simple and reliable way. Copyright © 2013 John Wiley & Sons, Ltd.
    NMR in Biomedicine 02/2013; · 3.45 Impact Factor