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Characterization of Engineered Cartilage constructs using Multiexponential T2 Relaxation Analysis and Support Vector Regression.
MedLine Citation:
PMID:  22166112     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increased sensitivity in the characterization of cartilage matrix status by magnetic resonance (MR) imaging, through the identification of surrogate markers for tissue quality, would be of great use in the noninvasive evaluation of engineered cartilage. Recent advances in MR evaluation of cartilage include multiexponential and multiparameteric analysis, which we now extend to engineered cartilage. We studied constructs developing from chondrocytes seeded in collagen hydrogels. MR measurements of transverse relaxation times were performed on samples after 1, 2, 3 and 4 weeks of development. Corresponding biochemical measurements of sulfated glycosaminoglycan (sGAG) were also performed. sGAG per wet weight increased from 7.74±1.34 µg/mg in week 1 to 21.06 ±4.14 µg/mg in week 4. Using multiexponential T<sub>2</sub> analysis, we detected at least three distinct water compartments, with T<sub>2</sub> values and weight fractions of (45 ms, 3%), (200 ms, 4%), and (500 ms, 97%), respectively. These values are consistent with known properties of engineered cartilage and previous studies of native cartilage. Correlations between sGAG and MR measurements were examined using conventional univariate analysis with monoexponential T<sub>2</sub> data, with individual multiexponential compartment fractions and sums of these fractions, through multiple linear regression based on linear combinations of fractions, and, finally, with multivariate analysis using the support vector regression (SVR) formalism. The phenomenological relationship between monoexponential T<sub>2</sub> and sGAG exhibited a correlation coefficient of r<sup>2</sup> = 0.56, comparable to the more physically-motivated correlations between individual fractions or sums of fractions and sGAG; the correlation based on the sum of the two proteoglycan-associated fractions was r<sup>2</sup>=0.58. Correlations between measured sGAG and those calculated using standard linear regression were more modest, with r<sup>2</sup> in the range 0.43 - 0.54. However, correlations using SVR exhibited r<sup>2</sup> values in the range 0.68 - 0.93. These results indicate that the SVR-based multivariate approach was able to determine tissue sGAG with substantially higher accuracy than conventional monoexponential T<sub>2</sub> measurements or conventional regression modeling based on water fractions. This combined technique, in which the results of multiexponential analysis are examined with multivariate statistical techniques, holds the potential to greatly improve the accuracy of cartilage matrix characterization in engineered constructs using noninvasive MR data.
Authors:
Onyi Nonye Irrechukwu; Ping-Chang Lin; David A Reiter; Remigio A Roque; Kenneth W Fishbein; Richard G Spencer
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-14
Journal Detail:
Title:  Tissue engineering. Part C, Methods     Volume:  -     ISSN:  1937-3392     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101466663     Medline TA:  Tissue Eng Part C Methods     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
National Institute on Aging, National Institutes of Health, Magnetic Resonance Imaging and Spectroscopy Section, Gerontology Research Center, Baltimore, Maryland, United States; irrechukwuon@mail.nih.gov.
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