Glycogen Quantification using MRI

Principal Investigator: Peter Van Zijl

The goal of this research is to develop and validate a novel MRI method for imaging glycogen contents of tissue. Glycogen is the main energy storage molecule of the body. Its non-invasive detection in situ in the human would have tremendous utility in the study of sports medicine (muscle glycogen depletion and repletion) as well as of many disorders, including but not limited to: Diabetes, malnutrition, weight disorders, exercise medicine, metabolism disorders, GSDs (Glycogen storage diseases, presently eight known), phosphofructokinase deficiencies, cardiac disease, ischemia, monitoring of diets, myocardial viability, muscular dystrophies, congenital myopathies, Cancer, alcoholism, hepatitis, liver disease, etc.

Presently, to our best knowledge, the only non-invasive approach to study glycogen levels and/or glycogen metabolism in vivo is Nuclear Magnetic Resonance Spectroscopy (NMR or MRS). Assessment of glycogen is done using non-invasive spectroscopy of natural abundance 13C-labeled isomers of glycogen in situ. A more invasive approach of providing infusions or supplements of 13C-labeled glucose that are metabolized to glycogen is also possible, but very cumbersome. 13C MRS is very insensitive compared to standard proton MRI, even when detected through the glycogen proton signal. Thus, even though it is presently possible to detect and monitor glycogen using nuclear magnetic resonance studies of 13C-labeled compounds, this is an insensitive approach that can only be done at course spatial resolution and requires specialized hardware not available at most MRI scanners.

We propose to develop a water-signal-based imaging approach that can image glycogen levels and changes therein using standard clinical MRI scanners and typical MRI resolutions. We have performed initial studies in water phantoms that show that the asymmetry in the magnetization transfer effect of water is proportional to glygogen concentration. We propose to use such magnetization transfer (MT) imaging, an approved MRI approach available on clinical MRI scanners, but now as a function of radiofrequency irradiation frequency offset combined with post-acquisition asymmetry analysis as a function of frequency offset with respect to water to demonstrate that this approach can also be accomplished in humans.

We will use two procedures to test and validate this: 1) measure changes in glycogen concentrations before and after eating a meal of known sugar content using our new MRI approach and compare this to simultaneous 13C in situ spectroscopy measurements (no infusions) for validation, and 2) measure changes in glycogen concentrations in a muscle pre and post excercise using our new MRI approach and compare this to simultaneous 13C in situ spectroscopy measurements (no infusions) for validation.