CEST IMAGING OF GLYCOGEN CONTENT COMPARED TO IN VIVO GLYCOGENOLYSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recently we proposed a method for imaging glycogen by MRI through the interaction of the OH protons of glycogen with the water protons which can be measured using magnetization transfer. Briefly, the exchangeable protons (OH) in the glycogen molecule can be selectively irradiated with the correct proton NMR frequency. Because of the fast chemical exchange with water protons, this spin label can be detected through the water line, and hence through the conventional MRI experiment. Like other magnetization transfer experiments, the key is to compare the bulk water signal in the presence of irradiation of the OH protons of glycogen with the bulk water signal at the opposite frequency with respect to the water resonance. The exchange of the OH protons in glycogen can be detected as a significant difference between the normalized water signal intensities obtained by irradiating at these two frequencies. More sophisticated approaches are also feasible. For example, instead of using the minimum of two frequencies, a full Z-spectrum can be obtained. The asymmetry in the z spectrum can be attributed to exchangeable OH groups. Our group at Johns Hopkins has the capability of performing these studies independently in our 3T system. However, we would like to integrate the 2H NMR methods available in this RR so we can measure glycogenolysis in our patients in our magnet in Baltimore, ship the samples to Dallas, and compare liver glycogenolytic rates in humans by CEST to liver glycogenolytic rates by deuterium.