Imaging technique may reduce cost, timeline of clinical trials in MS

“Think of a multiple sclerosis lesion as the tip of the iceberg,” says Dr. Alex Rauscher. “It’s not just what’s happening inside the lesion that we need to think about – what happens in the surrounding tissue affects the brain as well."

By using advanced, highly-sensitive magnetic resonance imaging (MRI) techniques, Dr. Rauscher and his team are hoping to better understand how damage occurs and how MRI can be used to monitor if new therapies are protective or have the potential to repair.

Multiple sclerosis (MS) causes breakdown of the brain's myelin, a substance that protects and insulates nerve fibres. If myelin is damaged, electrical signal transmission between neurons is impeded, leading to a range of symptoms, including numbness or weakness, vision loss, tremors, dizziness and fatigue.

Dr. Rauscher, an MRI scientist and Canada Research Chair in Developmental Neuroimaging, has focused his group's work on developing advanced MRI techniques that can visualize and measure damage in the brain due to MS, with emphasis on understanding the physics behind the MR images.

Dr. Rauscher's team uses a highly sensitive MRI technique called susceptibility mapping to investigate the magnetic properties of brain tissues. Susceptibility mapping can be used to detect changes in brain tissue composition, including damage or repair of myelin, or due to the presence of iron.

Initially, the bright appearance of MS lesions on susceptibility maps led researchers to believe that iron increases in lesions. Since iron in large amounts is toxic, researchers assumed that it contributes to the damage in MS and furthers the course of the disease.

However, research from Dr. Rauscher's lab, authored by PhD student Vanessa Wiggermann and published in 2013 in Neurology, suggested that the bright appearance of MS lesions on susceptibility maps may mainly be due to the breakdown of myelin, rather than due to an accumulation of iron.

To verify their previous findings and hypothesis, Dr. Rauscher’s team collaborated with researchers at the Center for Brain Research at the Medical University of Vienna, who are experts in understanding the biology of MS. In this collaboration, the team studied 15 post-mortem MS brain samples  using MRI, as well as chemical analysis of the tissues, to measure iron and myelin in MS lesions and surrounding tissues.

“We were able to show that only a few lesions contain diffusely distributed iron or iron-positive cells,” says Dr. Rauscher. “We determined that iron is not responsible for the bright appearance of MS lesions on susceptibility maps.”

Their research, published in the journal NMR in Biomedicine, concludes that the lesions themselves are only a part of the equation when it comes to the formation of the MRI signal.

“To use this technique in the future for measuring tissue damage and repair, it will be crucial to understand and correctly read the MRI data,” says Vanessa Wiggermann. "We demonstrated that values measured in MS lesions on susceptibility-sensitive MRI depend also on the state of the surrounding white matter due to the nature of this particular scan.”

“We believe that if we can understand how and why white matter changes in MS, and if we have techniques like susceptibility mapping to sensitively detect damage, we will also be able to measure whether new therapies protect or repair brain tissue,” Dr. Rauscher explains. “The more sensitive our techniques, the faster and at less cost we will be able to determine if a drug is effective. Imaging techniques that demonstrate the effectiveness of new treatments would be an invaluable asset in drug trials, and our recent work constitutes an important step toward such a technique.”  

The study was funded by the National MS Society and NSERC. Vanessa Wiggermann is supported by the MS Society of Canada.