Getting Better Visualization of Joint Cartilage through Cationic CT Contrast Agents

In its search to find new ways to treat osteoarthritis and other diseases, a research team has reported finding a new computed tomography (CT) contrast agent for visualizing the special distributions of glycosaminoglycans (GAGs)--the anionic sugars that account for the strength of joint cartilage.

Assessing the local variations in GAGs are of significant interest for the study of cartilage biology and for the diagnosis of cartilage disease such as osteoarthritis, which afflicts more than 27 million in people in the United States.

In the study, published in September 2009 online in the Journal of the American Chemical Society (JACS), researchers from Boston University (BU; Boston, MA, USA) described new contrast agents that selectively bind to the GAGs in articular cartilage. Articular or joint cartilage is the smooth hydrated tissue in 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.

To better see the differentiation between healthy and unhealthy cartilage, contrast agents provide the visual tool to evaluate GAG content. However, the current contrast agents used with computer tomography or magnetic resonance imaging (MRI) rely on limited diffusion of the anionic or negative ion-charged contrast agents into the target tissue, the study noted. Therefore, the researchers theorized that cationic contrast agents would be electrostatically attracted to anionic GAGs to provide a more sensitive technique for imaging cartilage. Furthermore, they focused on using the more widely accessible CT equipment because it can image cartilage and bone simultaneously, enable rapid three-dimensional reconstruction of the tissue, and achieve higher spatial resolution over shorter acquisition times compared to MRI systems.

The team synthesized three cationic or positive ion-charged iodine-based X-ray contrast agents. Using the femur of a rabbit, they reported gaining better and more specific images for the cartilage tissue than with current negative ion-charged contrast agents. "Compared to commercially available contrast agents under the same experimental conditions, these new cationic agents are three times more sensitive for imaging cartilage,” said Dr. Mark W. Grinstaff, Boston University professor of chemistry and biomedical engineering who led the team with Brian D. Snyder, M.D., Ph.D., an orthopedic surgeon at Children's Hospital and Harvard Medical School, both based in Boston.

Dr. Snyder noted that the ability to acquire information about localized GAG content, morphology and cartilage thickness on tissue samples will, in the future, aid in the diagnosis and treatment of osteoarthritis. Moreover, while the data presented a convincing case for continued development of cationic CT contrast agents, the researchers cautioned that the suitability for in vivo applications remains to be determined, adding that toxicity levels and radiation dosage will be the focus of future studies.

"However, the ability to characterize ex vivo cartilage samples is clearly evident,” the study authors concluded. "Currently obtaining data about the spatial distribution of biochemical components in tissue samples is largely accomplished using histology, which is destructive and time consuming, and thus the use of contrast agents in conjunction with CT imaging will result in readily available, nondestructive alternative to histology.”

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