NMR visibility of deuterium-labeled liver glycogen in vivo

Purpose: Deuterium metabolic imaging (DMI) combined with [6,6'-H-2(2)]-glucose has the potential to detect glycogen synthesis in the liver. However, the similar chemical shifts of [6,6'-H-2(2)]-glucose and [6,6'-H-2(2)]-glycogen in the H-2 NMR spectrum make unambiguous detection and separation difficult in vivo, in contrast to comparable approaches using C-13 MRS. Here the NMR visibility of H-2-labeled glycogen is investigated to better understand its potential contribution to the observed signal in liver following administration of [6,6'-H-2(2)]-glucose. Methods: Mice were provided drinking water containing H-2-labeled glucose. High-resolution NMR analyses was performed of isolated liver glycogen in solution, before and after the addition of the glucose-releasing enzyme amyloglucosidase. Results: H-2-labeled glycogen was barely detectable in solution using H-2 NMR because of the very short T-2 (<2 ms) of H-2-labeled glycogen, giving a spectral line width that is more than five times as broad as that of C-13-labeled glycogen (T-2 = similar to 10 ms). Conclusion: H-2-labeled glycogen is not detectable with 2H MRS(I) under in vivo conditions, leaving C-13 MRS as the preferred technique for in vivo detection of glycogen.