Destruction Of Myelin In Gray Matter Correlated With Severity Of Multiple Sclerosis, New MRI Method Shows

MRI
Researchers have devised a new MRI technique that gives them fast 3D images to track myelin loss in the gray matter of the brain. Photo courtesy of Shutterstock

Destruction of myelin in the white matter was long known to be the cause of multiple sclerosis (MS). But new research suggests that loss of myelin in the gray matter of the brain also leads to MS, and the loss is directly proportional to the severity of the disease. The study, which appears online in the journal Radiology, used magnetic resonance imaging (MRI) to study the effect of myelin loss in the progression of MS.

MS is an autoimmune disease of the central nervous system (CNS) characterized by several physical, mental, and psychological defects such as vision loss, speech problems, difficulty eating, and depression or unstable mood.

The condition is the result of formation of MS plaques. These plaques are formed when the insulation material, called myelin, around the nerve cells of the brain and spinal cord are destroyed by components of the immune system such as macrophages, microglia, or lymphocytes. The buildup of these plaques results in faulty transmission of messages between the brain and other parts of the body, leading to MS.

Since myelin is concentrated in the white matter of the brain, MS was considered a condition primarily involving this part of the brain. But recent studies have shown that myelin is also present in smaller amounts in gray matter, the brain's information processing center that is made up primarily of nerve cell bodies. While myelin concentration in the gray matter may be small, it is still important, as it protects the thin nerve fibers connecting neighboring areas of the brain cortex and is an important part of the CNS.

"The fact that MS patients lose myelin not only in white but also in gray matter has been proven by earlier post-mortem pathological studies," said Vasily L. Yarnykh, from the Department of Radiology at University of Washington in Seattle in a statement. "However, the clinical significance of the myelin loss, or demyelination, in gray matter has not been established because of the absence of appropriate imaging methods.”

Yarnykh and his team used an advanced MRI technique called macromolecular proton fraction (MPF) mapping that allowed them to get whole-brain maps and study the association between MS and demyelination in both white and gray matter.

"The method utilizes a standard MRI scanner and doesn't require any special hardware — only some software modifications," Yarnykh said. "MPF mapping allows quantitative assessment of microscopic demyelination in brain tissues that look normal on clinical images and is the only existing method able to evaluate the myelin content in gray matter.

Brains scans were taken of 30 MS patients, including 18 with relapsing-remitting MS (RRMS), the most common type of MS initially diagnosed, and 12 with the more advanced type of disease known as secondary progressive MS (SPMS). Brain scans of 14 healthy controls were also taken. 

Each participant underwent MRI on a 3-Tesla imager. The researchers then reconstructed 3-D whole-brain MPF maps to compare normal appearing white and gray matter to those with MS lesions. The results of the imaging technique were also compared with clinical tests characterizing neurological dysfunction in MS patients.

The results showed that MPF was significantly lower in both white and gray matter in RRMS patients compared with healthy controls, and was also significantly reduced in both normal appearing brain tissues and lesions of SPMS patients compared to RRMS patients with the largest relative decrease in gray matter. MPF in brain tissues of MS patients significantly correlated with clinical disability and the strongest associations were found for gray matter.

"The major finding of the study is that the loss of myelin in gray matter caused by MS in its relative amount is comparable to or even larger than that in white matter," Yarnykh said. "Furthermore, gray matter demyelination is much more advanced in patients with secondary progressive MS, and it is very strongly related to patients' disability. As such, we believe that information about gray matter myelin damage in MS is of primary clinical relevance." 

The advantage of this method is that it is fast and can provide information on the extent of damage in both gray and white matter and help to develop specific interventions based on them. The researchers now plan to see how myelin degradation occurs over time to better understand MS.

Source: Yarnykh  VL, Gangadharan  B, Maravilla  KR, et al. Fast Whole-Brain Three-dimensional Macromolecular Proton Fraction Mapping in Multiple Sclerosis. Radiology. 2014.

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