New contrast agents offer osteoarthritis insights

A Boston University-led research team has come up with a breed of contrast agents that might open the door to the use of CT to noninvasively diagnose osteoarthritis. These agents visualize the distribution of glycosaminoglycans, the anionic sugars that account for the strength of joint cartilage.

Assessing local variations in glycosaminoglycans (GAGs) is necessary to diagnose cartilage disease like osteoarthritis, which afflicts more than 27 million in people in the U.S.

"Compared with commercially available contrast agents under the same experimental conditions, these new cationic agents are three times more sensitive for imaging cartilage," said Mark W. Grinstaff, Ph.D., a Boston University associate professor of chemistry and biomedical engineering who led the team.

Only tests on animal tissue have yet been done, but early results have been encouraging, particularly since current image quality with both MR and CT are subpar.

In a paper published earlier this year in the Journal of the American Chemical Society, Grinstaff and colleague Dr. Brian D. Snyder, an orthopedic surgeon at Children's Hospital Boston and an associate professor of orthopedic surgery at Harvard, describe the new contrast agents, which selectively bind to the GAGs in articular cartilage. This cartilage is found at the ends of bones in load-bearing joints such as knees, hips, and shoulders.

The loss of GAGs from these joints is the hallmark of osteoarthritis, a degenerative joint disease in which wear or trauma results in damage to the cartilage surface. Contrast agents currently in use with CT and MR rely on limited diffusion of the anionic, or negative ion-charged, contrast into the target tissue, the study noted.

The Boston research team reasoned that more sensitive imaging of this joint cartilage might be possible through the use of cationic contrast agents, which are electrostatically attracted to anionic GAGs. They focused on CT because this modality, with the new agent, could image cartilage and bone simultaneously, potentially enabling 3D reconstruction of the structure. The team synthesized three cationic, or positive ion-charged, iodine-based x-ray contrast agents.

Animal tests showed that the experimental agents produced better and more speci¬fic images for the cartilage tissue than the current negative ion-charged contrast agents. Snyder noted that the ability to acquire data about localized GAG content, morphology, and cartilage thickness on tissue samples may, in the future, aid in the diagnosis and treatment of osteoarthritis. Future safety testing will focus on determining toxicity levels of the agents and radiation dosage needed to produce diagnostic images.