GD-DTPA(2-) AS A MEASURE OF CARTILAGE DEGRADATION

Glycosaminoglycans (GAGs) are the main source of tissue fixed charge d ensity (FCD) in cartilage, and are lost early in arthritic diseases. W e tested the hypothesis that, like Na+, the charged contrast agent Gd- DTPA(2-) (and hence proton T-1) could be used to measure tissue FCD an d hence GAG concentration, NMR spectroscopy studies of cartilage expla nts demonstrated that there was a strong correlation (r > 0.96) betwee n proton T-1 in the presence of Gd-DTPA(2-) and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equi librium model was examined as a means of quantifying FCD from Gd-DTPA( 2-) concentration, yielding a value 50% less but linearly correlated w ith 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-DTPA(2-) concentration, or a more sophisticated physical mode l could be developed. Spatial distributions of FCD were easily observe d in T-1-weighted MRI studies of trypsin and interleukin-1 induced car tilage degradation, with good histological correlation. Therefore, equ ilibration of the tissue in Gd-DTPA(2-) gives us the opportunity to di rectly image (through T-1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical s tudies demonstrated Gd-DTPA(2-) penetration into cartilage, suggesting that this technique is clinically feasible.