Gd-DTPA2- as a measure of cartilage degradation

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.