These authors contributed equally to this work.
Special Issue Research Article
Improved MR-based characterization of engineered cartilage using multiexponential T2 relaxation and multivariate analysis
Version of Record online: 29 JAN 2012
Copyright © 2012 John Wiley & Sons, Ltd.
NMR in Biomedicine
Special Issue: MRI in Tissue Engineering
Volume 25, Issue 3, pages 476–488, March 2012
How to Cite
Reiter, D. A., Irrechukwu, O., Lin, P.-C., Moghadam, S., Thaer, S. V., Pleshko, N. and Spencer, R. G. (2012), Improved MR-based characterization of engineered cartilage using multiexponential T2 relaxation and multivariate analysis. NMR Biomed., 25: 476–488. doi: 10.1002/nbm.1804
- Issue online: 20 FEB 2012
- Version of Record online: 29 JAN 2012
- Manuscript Accepted: 23 SEP 2011
- Manuscript Revised: 30 AUG 2011
- Manuscript Received: 4 APR 2011
- cartilage MRI;
- multiexponential T2;
- support vector machine;
- tissue engineering
Noninvasive monitoring of tissue quality would be of substantial use in the development of cartilage tissue engineering strategies. Conventional MR parameters provide noninvasive measures of biophysical tissue properties and are sensitive to changes in matrix development, but do not clearly distinguish between groups with different levels of matrix development. Furthermore, MR outcomes are nonspecific, with particular changes in matrix components resulting in changes in multiple MR parameters. To address these limitations, we present two new approaches for the evaluation of tissue engineered constructs using MR, and apply them to immature and mature engineered cartilage after 1 and 5 weeks of development, respectively. First, we applied multiexponential T2 analysis for the quantification of matrix macromolecule-associated water compartments. Second, we applied multivariate support vector machine analysis using multiple MR parameters to improve detection of degree of matrix development. Monoexponential T2 values decreased with maturation, but without further specificity. Much more specific information was provided by multiexponential analysis. The T2 distribution in both immature and mature constructs was qualitatively comparable to that of native cartilage. The analysis showed that proteoglycan-bound water increased significantly during maturation, from a fraction of 0.05 ± 0.01 to 0.07 ± 0.01. Classification of samples based on individual MR parameters, T1, T2, km or apparent diffusion coefficient, showed that the best classifiers were T1 and km, with classification accuracies of 85% and 84%, respectively. Support vector machine analysis improved the accuracy to 98% using the combination (km, apparent diffusion coefficient). These approaches were validated using biochemical and Fourier transform infrared imaging spectroscopic analyses, which showed increased proteoglycan and collagen with maturation. In summary, multiexponential T2 and multivariate support vector machine analyses provide improved sensitivity to changes in matrix development and specificity to matrix composition in tissue engineered cartilage. These approaches show substantial potential for the evaluation of engineered cartilage tissue and for extension to other tissue engineering constructs. Copyright © 2012 John Wiley & Sons, Ltd.