In the present work, our aim was the implementation of proton NMR spectroscopy methods optimized for glutamate detection and their application to Parkinson's disease, in which alterations of glutamate metabolism play a central role. For applications on the patient, a double quantum filter method and an approach related to two-dimensional (2D) spectroscopy have been implemented on a 3 Tesla whole body imager. In a following study including ten patients affected by Parkinson's disease and ten healthy controls, the latter method was applied for glutamate measurements in the lentiform nucleus (putamen and globus pallidus). No significant changes of glutamate levels could be shown comparing patients on or temporarily off levodopa (L-DOPA) treatment to healthy controls. Combined creatine/phosphocreatine showed a tendency to decreased values in patients. For application on the animal model, the method used on the patient was evaluated for measurements on the rat at 7 Tesla field strengths. A standard PRESS method with an echo time of 136 ms was used to study striatal glutamate changes in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. Spectra were acquired from the same animal before and after 6-OHDA treatment and following L-DOPA injection. No significant glutamate changes could be observed but a tendency to decreased choline values following lesion. Our results suggest that alterations in glutamatergic activity which have been shown before on this animal model using other methods are not reflected by an important change in total (intra- and extracellular) glutamate, as it is measured using in vivo proton MRS.
