The influence of myelin ultrastructure in determining magnetic resonance contrast

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Magnetic resonance imaging (MRI) is a powerful technique for studying the brain and spinal cord which is also called the central nervous system (CNS). The signal that MRI measures comes mainly from water - the location and behaviour of the water gives information about tissue structure. Despite the fact that MRI has been used to image the CNS for over three decades, the specific factors that contribute to the MRI signal are still poorly understood. For example, the cause of MRI contrast changes that happen during brain development needs more research. Also, variation in MRI contrast is seen in different brain and spinal cord regions, but the source of this signal variation is unknown. A major component of CNS tissue that varies structurally around the brain and spinal cord is myelin. Myelin is an insulating sheath that surrounds nerve cells - it makes signals travel quickly and is crucial to CNS function. The influence of myelin on MRI signal has not been studied in detail, but is likely very important. Myelin is made up of many layers of proteins and lipids. Because of the limitations of the MRI scanner, we cannot get signal from the myelin lipids and proteins. However, myelin also contains ~40% water which is found between the lipid/protein layers. This `myelin water' can be measured with a special advanced MRI method we have developed that has been proven to be related to the myelin lipid/protein layers. Given the widespread use of MRI, determining how myelin influences MRI contrast in the CNS is important. For example, regional variations in myelin lipid and protein content and differences in myelin thickness would influence MRI measurements. The long term goal of our research is to understand how tissue microstructure influences MRI contrast in the CNS. In the short term, our research will focus on determining how myelin structure drives MRI signal differences in normal tissue. Brains and spinal cords from healthy animals of various ages will get standard and advanced MRI scans. The characteristics of different cells inside the CNS will then be examined with a microscope and compared to the MRI scans. We also will study how changes to myelin structure impacts changes we can see with MRI. Brains and spinal cords that have structurally abnormal myelin will be studied with MRI and a microscope. Comparing what we see with the microscope to the MRI will help us understand variations of MRI signal linked to structurally abnormal myelin. This work is important because MRI is a commonly used imaging technique for studying the CNS and it is crucial to understand what determines contrast and causes signal variations. We will produce the first comprehensive atlas describing the relationship between MRI contrast and myelin structure in healthy CNS tissue. By assessing myelin that has been altered, we will identify what MR characteristics can differentiate structurally normal from structurally abnormal myelin.