Research interests

My research interests are focused on studying in vivo neurochemistry and biochemistry using non-invasive techniques, focuseing mainly on using NMR spectroscopy to measure energy metabolism.

1. Brain glycogen metabolism

Glycogen is the major storage form of glucose in mammals and its deranged metabolism is a major pathogenic factor in many human diseases. We are currently capable of measuring brain glycogen in rat brain at 9.4 Tesla and are extending these measurements to the human brain.

External Collaborators: Elizabeth R. Seaquist, M.D., Dept. of Medicine, DEM, U of MN; Louis Sokoloff, NIMH, NIH; Gerald A. Dienel, U of Arkansas;

2. NMR studies of glutamatergic action in the   brain

The high specificity of C-13 NMR permits to study glutamate and glutamine metabolism in great detail. We have previously shown that localized C-13 MRS of the human brain is possible at high magnetic fields with much improved sensitivity. This project is designed to elucidate glutamate metabolism and to demonstrate that glutamatergic action can be measured non-invasively using C-13 MRS, as well as astrocyte metabolism during focal activation.

Ext. Collaborators: P. Tuite, Neurology; Lester R. Drewes, Biochemistry, U of MN Duluth; Matthew Andrews, Biochemistry, U of MN Duluth; Kathryn F. LaNoue, Penn State, Hershey, PA; Susan Hutson, Wake Forest University, Wake Forest, NC;

3. NMR measurement of glucose transport in the human brain

Using  H-1 NMR spectroscopy, we have shown that glucose can be measured directly and non-invasively in the human brain. Preliminary results indicate that glucose transport models may not be sufficient in gray matter. We are currently extending these measurements to white matter and type I diabetes.

External Collaborator: Elizabeth R. Seaquist, M.D., Dept. of Medicine, DEM, U of MN;

• Diseases currently under investigation

Hepatic Encephalopathy - Glutamine is easily separated from glutamate at higher magnetic fields and thus detecting hepatic encephalopathy is a simple test in a matter of minutes

Diabetes (Hypoglycemia) - If it weren't for hypoglycemia, treatment of diabetes would be straightforward; we are investigating the role of brain glucose transport and glycogen metabolism in the brain's ability to properly detect hypoglycemia.

Adrenoleukodystrophy - The increased sensitivity at very high magnetic fields now allows a full characterization of the neurochemical profile in individual patients, suitable for potential treatment management.

Parkinson Disease - Glutamate excitotoxicity and antioxidant defenses are central to the current pathogenic theories of Parkinson's disease. We are exploring the potential and promises to specifically measure the substantia nigra in the brain.

Schizophrenia - The glutamate hypothesis in Schiziphrenia suggests there is an excitotoxic component in the pathogenesis of Schizophrenia. We are measuring the neurochemical profile in the frontal lobe.

Iron deficiency - Iron deficiency has devastating consequences for the cerebral defenses in the developing brain. We are studying normative brain development and the effect of iron deficiency thereon.

Selected publications

1. Terpstra M., Ugurbil K., Gruetter R. (2002) Direct in vivo measurement of human cerebral GABA concentration using MEGA-editing at 7 Tesla. Magn Reson Med 47, 1009-12.
2. Choi I. Y., Lee S. P., Kim S. G., Gruetter R. (2001) In vivo measurements of brain glucose transport using the reversible Michaelis-Menten model and simultaneous measurements of cerebral blood flow changes during hypoglycemia. J Cereb Blood Flow Metab 21, 653-63.
3. Seaquist E. R., Damberg G. S., Tkac I., Gruetter R. (2001) The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes 50, 2203-9.
4. Tkac I., Keene C. D., Pfeuffer J., Low W. C., Gruetter R. (2001) Metabolic changes in quinolinic acid-lesioned rat striatum detected non- invasively by in vivo (1)H NMR spectroscopy. J Neurosci Res 66, 891-8.
5. Pfeuffer J., Tkac I., Provencher S. W., Gruetter R. (1999) Toward an in Vivo Neurochemical Profile: Quantification of 18 Metabolites in Short-Echo-Time (1)H NMR Spectra of the Rat Brain. J Magn Reson 141, 104-20.

For a recent review of aspects not covered in the papers above, see also Gruetter R. (2002) In vivo 13C NMR studies of compartmentalized cerebral carbohydrate metabolism. Neurochem Int 41, 143-54.

Last updated: September 30, 2002