Noninvasive Imaging Method Can Help Predict Osteoarthritis
A new, noninvasive imaging method for early diagnosis of osteoarthri-tis and intervertebral disc degeneration capitalizes on the properties of a cartilage building block, using it as an inherent contrast agent.
 Alexej Jerschow, Ph.D. New York University |  Ravinder R. Regatte, Ph.D. New York University |
Loss of the building block glycosaminoglycan (GAG) typically marks the onset of osteoarthritis, which affects at least 20 million Americans.
Mapping the GAG concentration in vivo with chemical exchange saturation transfer—a method researchers call gagCEST—can help predict who is likely to get the disease in the next five years, said Ravinder R. Regatte, Ph.D., an assistant professor in the Department of Radiology at New York University (NYU) Langone Medical Center.
"If we can measure the early biochemical—GAG—changes before morphological changes occur, then we can provide these people with drugs to balance the biochemicals to prevent arthritis from developing," said Dr. Regatte, an author of a paper that appeared in the Feb. 19, 2008, issue of the Proceedings of the National Academy of Sciences. "Right now conventional radiographs are used to measure this disease progression and you can't see soft tissue clearly on the films," he said. "If there are any defects, you can't see them and you can't tell how much is actually lost."
Other GAG-monitoring techniques are based on MR imaging and either cannot directly map GAG concentrations or require administration of exogenous contrast agents, according to NYU chemistry professor Alexej Jerschow, Ph.D., another researcher on the study. NYU scientists worked with colleagues at Tel Aviv University in Israel.
"The current methods are not very specific about giving early warning signs—you want to have biochemical markers that tell you early that there is a chance that there will later be some dysfunction of a joint," said Dr. Jerschow. "If you can avoid administering a contrast agent, that is always better. The method we developed does not require one. It's relatively quick as well—maybe 10 minutes."
Method Uses Inherent Contrast
The new method doesn't require a contrast agent because it uses molecules and mechanisms that are already in the body. Knowing that GAG molecules have proton groups that are not tethered tightly, the researchers looked at whether proton exchange in the GAGs would allow GAG concentrations to be measured by MR imaging. The researchers investigated whether the GAG protons would become a natural contrast agent as they are separated from those of water during the process of chemical saturation.
Testing in tissue samples indicated that GAG protons indeed offered a type of contrast enhancement that allowed them to monitor GAGs through an MR scanner, said Dr. Jerschow. "We started with animal samples and since the method does not require an agent, we should be able to move quickly into practical application," he said. "The response from the musculoskeletal researchers and the imaging community has been very good and we see even more potential for this in the intervertebral disc, because conventional contrast agents are even less useful in the disc."
| MRI of the knee.  The measured glycosaminoglycan (GAG) concentration is indicative of the intactness of cartilage tissue. Image courtesy of New York University. |
At work on the study for nearly a year, the researchers maintain their method can not only diagnose and monitor disease but also help determine the efficacy of drug therapies. The next step in their study, they said, is to look at patients with different degrees of osteoarthritis and intervertebral disc degeneration. "For example, people who have undergone surgery," said Dr. Jerschow. "Samples have been histologically simplified and we will compare our indicators with other indicators of degeneration."
Ongoing multicenter trials as a part of the Osteoarthritis Initiative funded by the National Institutes of Health will acquire longitudinal MR imaging data from more than 4,000 human subjects in the next five years, said Dr. Regatte. These studies aim to specifically identify sensitive imaging biomarkers to distinguish knee osteoarthritis progression versus incidental osteoarthritis. Although the current imaging protocols are limited to conventional radiographs and morphology of cartilage, Dr. Regatte hopes gagCEST will be among the potential biochemical imaging methods used in the near future.
Dr. Regatte noted that gagCEST again offers an advantage over other biochemical imaging methods—sodium MR imaging, T1rho MR imaging and dGEMRIC (delayed gadolinium-enhanced MR imaging of cartilage)—that require use of exogenous contrast agents. He added, however, some more basic validations need to be performed before incorporating gagCEST into routine clinical scans. "We can already do it today on humans," Dr. Jerschow said. "The only issue is that at this point we are not 100 percent sure it is a more useful technique than what is already out there, but the preliminary findings are highly promising."
