Enhanced contrast medium helps diagnose multiple sclerosis
Researchers have found a new contrast agent that, when applied to animal models, enhances MRI visualization of tissue inflammation caused by multiple sclerosis. The agent could help diagnose the disease sooner, when treatment would have a greater effect.
Multiple sclerosis occurs when the immune system attacks the central nervous system, destroying the myelin sheath — a fatty layer that helps transfer the electrical signals responsible for nerve cell processing.
The new contrast agent, Gadofluorine M, is an amphiphilic macrocyclic gadolinium complex with a molecular weight of 1530 g/mol. It is better than the previously used contrast agent at detecting lesions because of its sensitivity to, and greater attraction of, extracellular matrix proteins. The substance has a higher local concentration, which allows it to attach to inflamed tissue, making lesions distinguishable on MRI scans.
Researchers at the Universities of Heidelberg and Würzburg in Germany examined tissue inflammation of the brain, spinal cord and optic nerves for lesions while comparing the new medium with the standard one, gadolinium-DTPA (Gd).
Sixty-three dark agouti rats were injected with myelin oligodendrocyte glycoprotein, an imitation of multiple sclerosis, which initiated tissue inflammation.
MRI images show an individual animal model injected with the new contrast agent, Gadofluorine M. Fourteen days after injection, a lesion is visible on a T1-weighted image of the coronal brain (a), whereas no lesion is visible on the T2-weighted image (b). An additional MRI is conducted 18 days after injection, revealing continuous lesion visibility with T1-weighted imaging (c) and still no visibility on T2-weighted imaging (d). Reprinted with permission of Brain.
The rats were grouped into those injected with Gd and those injected with the new contrast agent. They were viewed at different stages of disease progression using a Siemens Magnetom 1.5-T magnetic resonance unit, and the procedure included T1- and T2-weighted coronal sequencing.
The study showed that, compared with the rats injected with the new contrast agent, the rats injected with Gd showed considerably fewer lesions when viewed with T1- and T2-weighted sequencing. In addition, for those animals injected with the new contrast agent, T1-weighted images had significantly more lesion exposure compared with T2-weighted images.
The researchers found that T2-weighted images with Gd revealed a large number of lesions only when the disease had become more severe over time. Thus, Gd and T2-weighted sequencing, the standard clinical visualization techniques, have been drastically underestimating the quantity of lesions in the earlier stages of multiple sclerosis. Therefore, the new agent coupled with T1-weighted imaging provides a substantial means of detecting tissue inflammation.
Other methods to enhance lesion visibility included increasing Gd dosage, using a higher magnetic field strength or using a higher resolution of magnetic resonance sequencing. However, all of the methods failed to show the lesions with the same vividness in the early stages of the disease compared with the new agent with T1-weighted sequencing.
Although multiple sclerosis is incurable, diagnosing it earlier would allow for immediate treatment, which could slow disease progression. Additional tests on animal models are needed, but this early study could lead to clinical practice that prevents the symptoms of multiple sclerosis and other central nervous system diseases from intensifying.
Brain, September 2008, pp. 2341-2352.
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