Gd-DTPA2− as a measure of cartilage degradation

Authors

  • Adil Bashir,

    1. Continuum Electromechanics Group, Laboratory for Electromagnetic and Electronic Systems, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
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  • Martha L. Gray,

    1. Continuum Electromechanics Group, Laboratory for Electromagnetic and Electronic Systems, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
    2. Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts
    3. Arthritis Unit, Massachusetts General Hospital Boston, Massachusetts
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  • Deborah Burstein

    Corresponding author
    1. Continuum Electromechanics Group, Laboratory for Electromagnetic and Electronic Systems, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
    2. Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts
    3. Department of Radiology, Charles A. Dana Research Institute, Beth Israel Hospital and Harvard Medical School Boston, Massachusetts
    • Radiology Research, DA-705, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215
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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.

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