Our approach to imaging the glycosaminoglycan (GAG) component of cartilage is based on the fact that since GAGs have abundant charged side groups that confer a negative fixed charge to the cartilage matrix, mobile ions will distribute in the tissue to reflect the local GAG concentration. In order to use proton MRI for detection of the ion, we used the MRI contrast agent Gd-DTPA 2-. The logic for the method is as follows: Gd-DTPA 2- will distribute into areas in cartilage that are depleted of GAG at a higher concentration than in areas of high GAG. Gd-DTPA 2- has concentration dependent effects on the magnetic resonance relaxation time T1; therefore T1 images in presence of Gd-DTPA2- reflect the tissue GAG concentration. We call this Gd-DTPA 2- enhanced method dGEMRIC (delayed Gd-DTPA 2- Enhanced MRI of Cartilage). For more information on the protocol issues in the application of dGEMRIC for both in vitro and in vivo applications, please refer to the protocol section of this website.

rc image 002This figure illustrates the basis of dGEMRIC: The GAG are represented by the yellow negative signs fixed to the cartilage matrix. The mobile negative ions, represented by the red negative signs (in this case Gd-DTPA 2-) will distribute in higher concentration in areas depleted of GAG.

Therefore, T1 in the tissue, which is dominated by the Gd-DTPA 2- concentration, will be reflective of the GAG distribution in the tissue.

If the tissue is in equilibrium with the Gd-DTPA 2-, the absolute GAG concentration can be determined using a modified biophysical theory of ion distribution in tissue.