A new computational tissue model from Dr. Alex Rauscher and his team has enabled the researchers to quantify brain myelin and iron from MRI scans, offering new clues as to the role of myelin and iron in tissue damage and disease progression in multiple sclerosis (MS). Published recently in the journal NMR Biomedicine, their paper reveals a difference in brain iron between people with MS, their healthy siblings, and unrelated controls.
MS is an autoimmune disease that occurs when the body’s immune system attacks myelin, the fatty material that insulates neurons and enables rapid transmission of electrical signals. When myelin is damaged, communication between the brain and other parts of the body is disrupted, leading to vision problems, muscle weakness, difficulty with balance and coordination, and cognitive changes.
“Iron is necessary for the production of myelin,” Dr. Rauscher explains. “Myelin-producing cells—known as oligodendrocytes—contain the highest concentration of iron in the brain.”
When these cells die, both myelin and iron in the brain are lost, making these two substances potential imaging markers for MS progression. However, in MRI, myelin and iron produce a very similar effect on the imaging signal, making it very difficult to quantify the two substances.
Knowing that the effects of myelin on the MRI signal depend on the angle between the tissue and the MRI scanner’s magnetic field—a phenomenon known as “orientation effect”—Dr. Rauscher and his team, including graduate students Jon Doucette and Daniel Kor, developed a computational model of the signal that takes iron, myelin and tissue orientation into account. As a result, they are now able to quantify myelin and iron with MRI. Applying the technique to patients with MS, healthy siblings of patients, and unrelated controls, they found loss in myelin and iron in the MS group (as expected). In the healthy siblings, who have an increased risk of MS, they found that iron is increased compared to the unrelated healthy controls.
“The orientation effect is essential for determining iron and myelin content,” explained Dr. Rauscher. “Without the orientation effect, we wouldn’t be able to separate the influence of the two substances on the MRI signal. Our ability to measure both could be an avenue to a new marker for disease progression in MS. Such marker would be extremely valuable for treatment trials in progressive MS.”
Dr. Rauscher’s work has wider implications: myelination occurs rapidly during early brain development, and quantifying early myelination may allow the prediction of developmental milestones in babies born preterm.
“We hope that in understanding how myelin changes across the lifespan, we can understand how it changes in the context of diseases such as MS,” said Dr. Rauscher. “The more we can predict changes in the brain based on imaging data, the more we can simplify and reduce the cost of clinical trials and intervene sooner in the disease course.”
This research is part of a larger project to understand the effects of various tissue properties on the images produced by different MRI applications. This research is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the American National MS Society.