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Interview with Dr. Susan Gauthier about her work on the MRI technique myelin-water fraction imaging for MS research - part 1

Gauthier & Vartanian MS AAN 2014 part 1

Interview by Dr. Timothy Vartanian, Director of the Judith Jaffe Multiple Sclerosis Center, with Dr. Susan Gauthier, Associate Professor in Neurology at the Weill Cornell Medical College (NY) and Director of Clinical Research at the Judith Jaffe Multiple Sclerosis Center.

The most important issue in MS currently is the question why MS patients progress into the progressive stage of the disease, Dr Gauthier says. This is the unmet need we need to go into. The two main hypotheses why people progress are i) years of demyelination leave the axons vulnerable to degeneration, and ii) chronic activation of immune cells, called microglia, within the brain, which can be toxic to the neurons. The two hypotheses could co-exist. The research tools used to address this issue includes the MRI technique myelin-water fraction imaging, which allows us to quantify myelin in white matter, allowing us to follow it over time. Also PET is used to label microglia in the brain. Both techniques are used (separately and joint) to look at earlier stages of MS, follow how these measures change over time in a relapse-remitting MS patient, and then follow these into progressive patients, to see if and how these dynamics change. There may be a more widespread activation of microglia in these latter patients and Dr Gauthier hopes to be able to measure that. Measuring myelin in vivo is important, as it can be used as a biomarker in clinical studies to determine re-myelination. There are not many options for measuring myelin in a clinical setting. Dr. Gauthier chose this method as MRI is the least invasive imaging technology, and myelin-water fraction has the most pathological specificity to myelin. It is not an easy technique, it has been around for 25 years and has limitations, which is why it took so long to develop it for clinical application. Data gathering is very long (30 min), and data analysis is very difficult. We have been working on both these bottlenecks to turn the technology into a clinically feasible technique. Now, we can acquire the data in 10 min, and soon we will be able to do this in 6.5 min. For processing data, we have developed very nice myelin maps, much less noisy than the old ones. Swelling caused by edema can influence measurements, using alternative techniques as well as our technique, but we have designed methods to deal with that, to filter this out. We just completed a cross-sectional study with around 140 early stage rrMS patients, investigating the myelin dynamics throughout the white matter. Modeling revealed two peaks: one representing lesions, another normal white matter. This allows us to study what is driving the changes in these two regions. Longer disease and disability are correlated to lower myelin-water fractions within lesions, but also in seemingly normal white matter regions. This could mean that these patients are less able to repair demyelinated neurons, or they are more actively demyelinated.