Thursday, July 28, 2011

Love is stronger than hate: a story of two contrast agents

The ability to image cartilage is important for diagnosis and analysis of a joint during arthritis. Normal X-rays cannot “see” cartilage because it can’t refract the X-rays like bone tissue can. In other words, it’s invisible. Until recently.

Scientists decided to take advantage of the fact that cartilage tissue is negatively charged (anionic, in science terms), due to the abundance of glycosaminoglycans (read: carbohydrate and sugar molecules) that help keep the tissue hydrated and bouncy to protect your bones. The dyes they invented, however, function based on repulsion. They work on the principle that anionic dyes will not go into highly anionic tissue, so a lack of dye equals healthier cartilage tissue.

This research decided to examine whether positively-charged dyes worked better, worse, or about the same as their anionic counterparts. Their hypothesis was that the attraction forces between negative and positive charges would create better dye interactions, and therefore better imaging, in cartilage tissue. To do this experiment, they took explants – round “plugs” – of bovine cartilage tissue and soaked them in both anionic (2 types) and cationic (1 type) dyes. They were able to evaluate all three dyes on each explant because the dye will naturally diffuse out of the tissue over time. Between each dye, the explants were allowed 24 hours of “wash-out” time to remove the dye, and were imaged to confirm that the dye was undetectable compared to the baseline measurements for each sample.

They imaged these cartilage tissues using a microCT machine – a kind of glorified X-ray device - that can detect these dyes, and analyzed the resulting images.

As predicted, they found that the positively-charged dye gave them better contrast between cartilage and non-cartilage tissue. Even better, though, the cationic dye accurately reflected the natural tissue distribution of GAGs within each cartilage plug, while neither anionic dye was able to recapitulate that structure.

This finding is good news for studying and tracking cartilage health in people with osteoarthritis. Claims by the authors that this discovery could also lead to new therapies might be a far stretch, but if they come up with a good therapeutic idea, I’ll take it.

Article Cited:
Bansal, PN et al. “Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage”. OA & C. Vol. 19, Issue 8, pp. 970-976.

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