MRI study shows severity of MS tied to loss of myelin in gray matter

The loss of myelin in the brain’s gray matter is closely tied to the severity of multiple sclerosis (MS) and the resulting disability, according to a study published online September 10 in Radiology.

The findings could have important applications in clinical trials and treatment of the degenerative inflammatory brain disease, the researchers said. They utilized a new MRI technique, macromolecular proton faction (MPF), and a faster method for whole-brain mapping.

"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," lead researcher Vasily L. Yarnykh, PhD, associate professor in the Department of Radiology at the University of Washington in Seattle, said in a statement. "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 new method that researchers used does not require special hardware, only some software modifications and a standard MRI scanner. "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," said Yarnykh.

MPF provides information on the content of biological macromolecules – molecules present in tissues and composed of a large number of atoms, such as proteins, lipids and carbohydrates. New improvements now allow for faster generation of whole-brain maps that reflect the macromolecular content in tissues.

Yarnykh said that although the myelin content in gray matter is small, it is still extremely important to proper function, because it enables protection of thin nerve fibers connecting neighboring areas of the brain cortex.

The loss of of myelin, the fatty protective sheath around nerve fibers, is characteristic of MS. The condition has been known to damage the myelin of the brain’s white matter, where there is more of it. However, myelin also is present in smaller quantities in gray matter, the brain’s information processing center made up mainly of nerve cell bodies.

Researchers looked at 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). They also included 14 healthy control participants. All participants underwent an MRI on a 3-Tesla scanner. Researchers reconstructed 3D whole-brain MPF maps to look at normal-appearing white matter, gray matter and MS lesions and compare the results of the participants.

The study found MPF could detect a lower amount of gray matter in RRMS and SPMS patients, compared with healthy participants. MPF detected that gray matter was reduced in both the lesions and normal-appearing brain tissues of both groups of patients, the authors said.

Yarnykh and colleagues wrote that the their findings demonstrate the use of MPF as a myelin biomarker in MS.

“Because it is a disease in which demyelination is a key pathologic substrate of neural tissue damage, MS represents a primary area for potential clinical applications of fast MPF mapping,” the authors wrote.