Author(s): Bashir A, Gray ML, Burstein D
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Abstract Glycosaminoglycans (GAGs) are the main source of tissue fixed charge density (FCD) in cartilage, and are lost early in arthritic diseases. We tested the hypothesis that, like Na+, the charged contrast agent Gd-DTPA2- (and hence proton T1) could be used to measure tissue FCD and hence GAG concentration. NMR spectroscopy studies of cartilage explants demonstrated that there was a strong correlation (r > 0.96) between proton T1 in the presence of Gd-DTPA2- and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equilibrium model was examined as a means of quantifying FCD from Gd-DTPA2- concentration, yielding a value 50\% less but linearly correlated with the validated method of quantifying FCD from Na+. These data could be used as the basis of an empirical model with which to quantify FCD from Gd-DTPA2- concentration, or a more sophisticated physical model could be developed. Spatial distributions of FCD were easily observed in T1-weighted MRI studies of trypsin and interleukin-1 induced cartilage degradation, with good histological correlation. Therefore, equilibration of the tissue in Gd-DTPA2- gives us the opportunity to directly image (through T1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical studies demonstrated Gd-DTPA2- penetration into cartilage, suggesting that this technique is clinically feasible.
This article was published in Magn Reson Med
and referenced in Journal of Arthritis