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: Evaluation of mechanical characteristics of cartilage by magnetic resonance imaging would provide a noninvasive measure of tissue quality both for tissue engineering and when monitoring clinical response to therapeutic interventions for cartilage degradation. We use results from multiexponential transverse relaxation analysis to predict equilibrium and dynamic stiffness of control and degraded bovine nasal cartilage, a biochemical model for articular cartilage. Sulfated glycosaminoglycan concentration/wet weight (ww) and equilibrium and dynamic stiffness decreased with degradation from 103.6 ± 37.0 µg/mg ww, 1.71 ± 1.10 MPa and 15.3 ± 6.7 MPa in controls to 8.25 ± 2.4 µg/mg ww, 0.015 ± 0.006 MPa and 0.89 ± 0.25MPa, respectively, in severely degraded explants. Magnetic resonance measurements were performed on cartilage explants at 4 °C in a 9.4 T wide-bore NMR spectrometer using a Carr-Purcell-Meiboom-Gill sequence. Multiexponential T2 analysis revealed four water compartments with T2 values of approximately 0.14, 3, 40 and 150 ms, with corresponding weight fractions of approximately 3, 2, 4 and 91%. Correlations between weight fractions and stiffness based on conventional univariate and multiple linear regressions exhibited a maximum r(2) of 0.65, while those based on support vector regression (SVR) had a maximum r(2) value of 0.90. These results indicate that (i) compartment weight fractions derived from multiexponential analysis reflect cartilage stiffness and (ii) SVR-based multivariate regression exhibits greatly improved accuracy in predicting mechanical properties as compared with conventional regression. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
    NMR in Biomedicine 02/2014; · 3.45 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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantitative assessment of desmoplasia in pancreatic ductal adenocarcinoma (PDAC) may be critical for staging or prediction of response to therapy. We performed quantitative magnetization transfer (qMT) MRI measurements in 18 mouse xenograft tumors generated from three PDAC cell lines. The qMT parameter bound proton fraction (BPF) was found to be significantly higher in tumors grown using the BxPC-3 cell line (5.31 ± 0.87, mean ± standard deviation) compared with the BPF measured for tumors grown from Panc-1 (3.65 ± 0.60) and Capan-1 (1.50 ± 0.58) cell lines (P < 0.05 for each comparison). Histologic measurements demonstrated a similar trend; BxPC-3 tumors had significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.21 ± 2.10) compared with Panc-1 (2.88 ± 1.13) and Capan-1 (1.69 ± 1.01) tumors. BPF was well correlated with quantitative fibrosis levels (r = 0.77, P < 0.01). Our results indicate that qMT measurements offer the potential to noninvasively quantify fibrosis levels in PDAC mouse xenograft models and thus serve as a valuable in vivo biomarker of desmoplasia in PDAC. Copyright © 2013 John Wiley & Sons, Ltd.
    NMR in Biomedicine 08/2013; · 3.45 Impact Factor