Creation of an atlas to study the role of myelin in normal brain function

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Quantitative magnetic resonance imaging (MRI) is far more reproducible and interpretable than qualitative MRI. This program is focused around a quantitative MRI technique called myelin water imaging (MWI), which produces a measurement related to myelin content (myelin water fraction, MWF). ******There are large gaps in our knowledge of myelin characteristics in the healthy human brain, largely due to the lack of a sensitive, specific, in vivo myelin measurement technique. A better understanding of the normal variation and natural factors affecting myelin content and function would be invaluable to the fields of biology and neuroscience. ******The long-term objective is to create a quantitative MWF atlas in healthy human brain across a wide range of individuals to study the role of myelin in normal brain function.******The short-term objectives are to:******1. Develop and optimise MWI for a state-of-the-art MRI scanner***We will implement and optimise a MWI sequence for a Philips 3 Tesla MRI scanner currently under installation. We will increase the number of echoes, decrease echo spacing, balance spin and gradient echoes, and employ alternate data sampling schemes.******2. Validate MWI as a function of myelin sheath thickness***We will compare MWF measurements from fixed tissue samples to electron microscopy measurements of the myelin sheath thickness as well as other quantitative MRI techniques. We will also compare in vivo MWF measurements to parameters related to myelin content and thickness derived from other advanced MRI sequences.******3. Extend MWI to work across other MRI scanners from different vendors***We will collaborate with other sites to develop MWI for other major MRI vendors, and compare measurements between machines. This will include understanding and characterising the effects of gradient strengths, radio frequency pulse shapes, and parallel imaging schemes.******4. Tackle the technical considerations of creating a healthy myelin atlas***Data from healthy participants will be leveraged from existing studies, as well as collected prospectively. We will address issues related to registration, warping, and segmentation using a combination of commercially available tools and in-house designed software. ******5. Use the myelin atlas to characterize normal variation in myelin levels between individuals***We will use the myelin atlas to determine the range of myelin content within the normal population, and dependencies on age, education, brain structure, tract size, and associated grey matter structure size.******Significance of the proposed research***The proposed research program is focused on studying the role of myelin in normal brain function. It will help to broaden our understanding of myelin biology and physiology. The methods employed here can be further applied to a wide range of other quantitative imaging techniques and parameters, providing information about additional biological aspects of the central nervous system. **