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By mapping the concentration of glycosaminoglycans (GAG) in vivo, a novel, noninvasive MRI technique provides a non-invasive way to diagnose and monitor degenerative joint disease. by Karla Gale

By mapping the concentration of glycosaminoglycans (GAG) in vivo, a novel, noninvasive MRI technique provides a non-invasive way to diagnose and monitor degenerative joint disease. The technique may also be useful for diagnosing disorders in tissues as disparate as 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," Dr. Alexej Jerschow, 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."

The current 'gold-standard' for mapping GAG, delayed gadolinium-enhanced MRI contrast, is hampered by the need for exogenous contrast material, poor reproducibility, and delayed diffusion into cartilage, Dr. Jerschow explained. Other imaging technologies are limited by long imaging time, lack of specificity, and the need for special hardware.

"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," the researcher added. "It is also relatively easy to implement on clinical scanners, and we therefore expect it to find widespread application."

The scientists chose cartilage to demonstrate that gagCEST MRI is sensitive to GAG concentration variations, "based on the labile protons residing on the GAGs."

In one experiment, they immersed one side of a fresh bovine patella in a trypsin bath for two periods of 60 minutes, to release GAG from proteoglycan molecules. MRI images demonstrated sequential decreases in signal correlated with depletion of GAG after each treatment, the investigators report in the Proceedings of the National Academy of Sciences for February 12th.

The researchers also conducted gagCEST MRI on a patellofemoral knee joint of a 30-year-old man with knee pain, which "displayed a clear demarcation of a cartilage lesion on the medial facet."

Dr. Jerschow predicts that gagCEST MRI will be particularly useful for detecting intervertebral disc disease, because "contrast agents do not diffuse into the nucleus of a disc."

He and his colleagues are also in the planning stages of adapting the technique for the assessment of heart valves and corneas. "GAGs in heart valves regulate water content, biomechanical function, and flexibility," he commented, so "monitoring the concentration of GAG can give early warning signs of failure."

"Similarly, GAG in corneas controls water content and flexibility, thereby providing favorable optical properties."


Source: Reuters