Iron in brain tissue influences myelin measurements with MRI

Dr. Alex Rauscher and his team are engaged in a long-term project to understand the effects of various tissue properties on the images produced by different magnetic resonance imaging (MRI) applications. His newest work, with postdoctoral fellow Dr. Christoph Birkl and published in the journal NeuroImage, offers a new perspective on the role of iron in myelin water imaging (MWI) and challenges existing interpretations of MWI findings in research literature.

MWI is an imaging technique that was first developed at the University of British Columbia by Dr. Alex MacKay in 1994. Because conventional MRI alone cannot distinguish between inflammation, demyelination, remyelination and axonal damage in diseases like multiple sclerosis (MS), Dr. MacKay and colleagues developed new techniques, including MWI, affording researchers a higher level of specificity and the ability to better understand the underlying processes occurring in neurological disease and traumatic brain injury. Dr. Rauscher and colleagues continue to build on MWI and related approaches, further honing the ability of imaging technology to reveal the hidden complexity of brain tissue and function in health and disease.

“Iron maintains a systematic and considerable bias in MWI,” explained Dr. Birkl. “In this study, we looked at whether changes in iron levels in the brain’s white matter can lead to altered results in MWI. We found that removing the iron but not otherwise altering the myelin in postmortem brain tissue resulted in a 28 per cent reduction in myelin signal strength.”

Myelin is a fatty, protein-rich insulation that insulates neurons, enabling efficient communication of electrical signals across brain regions. Myelin-producing cells contain the highest concentration of iron in the brain, making iron a potential marker for imaging in demyelinating diseases such as MS, Huntington’s disease, or Parkinson’s disease.

“We are interested in how myelin and iron influence the MRI signal,” said Dr. Rauscher. “A better understanding of these mechanisms will eventually allow us to develop imaging biomarkers that can be used in diagnosis or in clinical drug trials.”

The researchers used two MWI techniques: the Carr-Purcell-Meiboom-Gill (CPMG) sequence, the gold-standard but much slower approach to mapping myelin, and a much faster technique developed by Dr. Rauscher in 2011, which is based on the  Gradient Echo Spin Echo (GRASE) sequence.

“This is the first study to look at the influence of iron extraction on MWI,” said Dr. Rauscher. “We had expected the GRASE sequence to show greater sensitivity in  iron changes in the brain, but to our surprise both techniques produced similar results. This leads us to believe that iron and myelin should be quantified independently in order to create a robust picture of degeneration or remyelination.”

“We hope this finding triggers more research into the role of iron in quantitative MRI,” said Dr. Birkl. “We are currently working on making MRI more specific by developing methods that can measure iron and myelin independently.”

This research is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), the MS Society of Canada, and the National MS Society. Dr. Birkl is supported by the Erwin Schrödinger Fellowship of the Austrian Science Fund.