Taking OA Imaging to the Next Level
Osteoarthritis (OA) damages joint cartilage and the surrounding bone. Treatment for established OA is limited to easing symptoms, but scientists around the world are looking for ways to stop the disease’s progression. However, seeing the cartilage inside the joint through existing technologies has limited researchers’ ability to determine if their experimental treatments are working. Through an Arthritis Foundation-funded project, scientists at the Georgia Institute of Technology in Atlanta have developed a new imaging technique that may help other investigators analyze the results of their drug studies.
What Problem Was Studied?
Until now, measuring OA disease progression was limited primarily to X-ray analysis. In humans, radiologists can measure joint space narrowing due to cartilage loss, but when dealing with the small animals used in arthritis research, this method is limited at best. So when dealing with laboratory animals, scientists would kill the animal, remove the cartilage from the joint, and look for changes under the microscope. Marc Levenston, PhD, and his team used Arthritis Foundation, National Institutes of Health, and National Science Foundation grants to develop a method of visualizing small variations in cartilage of animals without having to destroy the cartilage in the process.
What Was Done in the Study?
Proteoglycans comprise 5% to 10% of articular cartilage and regulate its mechanical properties. Dr. Levenston and team developed an imaging tool called EPIC-µCT to monitor proteoglycan content in cartilage, thereby allowing the generation of a three-dimensional image of the cartilage. By detecting proteoglycan content and distribution, the technique reveals information about the thickness and composition of cartilage – both of which are important for monitoring the progression and treatment of OA.
To determine whether this imaging tool is able to detect changes in cartilage, tissue removed from cows was treated with interleukin-1, a naturally occurring cytokine known to induce cartilage damage. The EPIC-µCT was used to measure the proteoglycan content in the cartilage before and after exposure to interleukin-1. In a second experiment, rabbit joints were visualized using the new technique to determine if the tool could indeed image cartilage of an intact joint from a small animal.
What Were the Study Results?
The research team was successful in identifying very small changes in the cartilage from cows using the EPIC-µCT. Furthermore, they were able to obtain three-dimensional images of intact rabbit joints.
What Does This Mean to People With Arthritis?
Noninvasive techniques to detect tissue changes could, according to Levenston, “dramatically improve upon existing evaluation options for monitoring the efficacy of OA treatments and cartilage repair strategies.” He now continues his work at Stanford University in California and will use the technique to examine the thickness and composition of cartilage in rat joints, which are substantially smaller than rabbit joints. Because rats are commonly used in biomedical research, this will be of huge benefit in evaluating the efficacy of new pharmaceutical treatments. Although the team has not yet been able to image the joints of living animals, they hope to eventually be able to study the effects of treatment over time in live laboratory animals.
“Although it is not clear yet whether this approach will be valuable clinically, it is a powerful research tool for scientists studying potential therapies,” Levenston says.
Palmer AW, Guldberg RE, Levenston ME. Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. PNAS 2006;103:19255-60.
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