Project Summary The liver is responsible for maintaining blood glucose homeostasis. It is able to deposit large amounts of glucose in the form of glycogen and release glucose rapidly from its glycogen storage when needed. The hepatic glycogen metabolism maybe altered in diseases such as glycogen storage disorders, diabetes mellitus, and liver cirrhosis. Liver biopsy allows direct quantification of glycogen concentration, but it is highly invasive and cannot easily be repeated. 13C nuclear magnetic resonance (NMR) spectroscopy provides a non-invasive way to detect glycogen in the liver, but it is not clinically feasible due to the requirement of specialized imaging hardware. Recently, we have discovered a new contrast mechanism that allows the detection of glycogen based on its nuclear Overhauser enhancement (GlycoNOE). This method enables us to detect glycogen in vivo using standard MRI hardware. In our initial mice study, we found a linear relationship between glycoNOE signal and glycogen concentration and demonstrated that the change in liver glycogen could be measured dynamically. In this project, we aim to develop a new imaging technique to utilize this contrast mechanism in the human liver. To achieve this we will (1) develop and optimize a fast, 3D free-breathing, fat-water separated imaging approach that is suitable for glycoNOE detection in the human liver; (2) compare the NOE signal measured at fed and fasting state to validate that the change in signal reflects the change in glycogen content; and (3) dynamically measure the change of glycogen upon glucagon injection, which further validates the glycoNOE signal and also measures the rate of glycogen degradation. The new imaging technology will be applicable to brain and body imaging based on the nuclear Overhauser enhancement / chemical exchange processes. By providing a non-invasive, real time measure of the change in glycogen level in the liver, it will be possible to study glycogen metabolism in health and in diseases such as diabetes mellitus, glycogen storage diseases, and other liver conditions.