MRI Looks at GAG to Evaluate Joint Disease

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A novel MRI technique has been shown to provide a noninvasive way to diagnose and monitor degenerative joint disease by mapping the concentration of glycosaminoglycans (GAG) in vivo, according to a recent report from Reuters Health. The method may also have useful applications in diagnosing disorders in a range of tissues, including cartilage, heart valves, and corneas.

"The early monitoring of the GAG concentration will allow one to provide preventive diagnostics, as well as a tool for monitoring the efficacy of potential drug therapies," Alexej Jerschow, PhD, at the New York University School of Medicine, told Reuters Health. "Measuring GAG concentrations in vivo will also allow us to better understand the mechanism of diseases."

Delayed gadolinium-enhanced MRI contrast, which represents the current approach to mapping GAG, is hampered by the need for exogenous contrast material, poor reproducibility, and delayed diffusion into cartilage, Jerschow said. Long imaging time, lack of specificity, and the need for special hardware also limit other imaging technologies.

"The gagCEST method (chemical exchange dependent saturation transfer) of measuring GAG does not require the administration of exogenous contrast agent, and its only disadvantage is a somewhat reduced sensitivity compared to normal MRI images," Jerschow said. "It is also relatively easy to implement on clinical scanners, and we therefore expect it to find widespread application."

Cartilage was selected to demonstrate that gagCEST MRI is sensitive to GAG concentration variations "based on the labile protons residing on the GAGs."

In one experiment, one side of a fresh bovine patella was submerged in a trypsin bath for two periods of 60 minutes, to release GAG from proteoglycan molecules. MRI images showed sequential decreases in signal correlated with depletion of GAG after each treatment, according to a report in the Proceedings of the National Academy of Sciences.

Additionally, the scientists conducted gagCEST MRI on a patellofemoral knee joint of a 30-year-old man who suffered from knee pain, which "displayed a clear demarcation of a cartilage lesion on the medial facet."

In the future, GagCEST MRI is expected to be particularly useful for detecting intervertebral disk disease because "contrast agents do not diffuse into the nucleus of a disk," Jerschow said. His team is planning to adapt the technique for the assessment of heart valves and corneas.

"GAGs in heart valves regulate water content, biomechanical function, and flexibility, [so] monitoring the concentration of GAG can give early warning signs of failure," Jerschow said. "Similarly, GAG in corneas controls water content and flexibility, thereby providing favorable optical properties."