Assess the feasibility of proton MR spectroscopic imaging (H-1-MRSI) of the striatum (putamen and caudate nucleus) in patients with Parkinson's disease and evaluate striatal neuronal density. Proton MRSI of the striatum and thalamus with 2 cc spatial resolution was performed in 10 patients with Parkinson's disease, I patient with atypical parkinsonism, and 13 control subjects. Single voxel proton MR spectra with signals from choline metabolites (Cho), creatine metabolites (Cr), and the putative neuronal marker, N-acetyl-aspartate (NAA), were obtained from the putamen and thalamus, but not the caudate nucleus, of patients with parkinsonism and control subjects. Metabolite ratios in controls and patients were: in putamen NAA/ Cho 1.70 +/- 0.25 vrs 1.74 +/- 0.32, NAA/Cr 2.80 +/- 0.79 vrs 2.36 +/- 0.42, Cho/Cr 1.63 +/- 0.25 vrs 1.39 +/- 0.3; in thalamus, NAA/Cho 1.78 +/- 0.15 vrs 1.62 +/- 0.22, NAA/Cr 2.78 +/- 0.34 vrs 2.64 +/- 0.41, Cho/Cr 1.57 +/- 0.25 vrs 1.65 +/- 0.28. There were no statistically significant differences between patients and controls. The putaminal NAA/Cho ratio of the single subject with atypical parkinsonism was lower than that of 9 of the 10 patients with classic Parkinson's disease and 11 of the 13 control subjects. Likewise, the putaminal NAA/ Cr ratio in the single subject with atypical parkinsonism was lower than that of 7 of the patients with Parkinson's disease and 10 of the 13 control subjects. Proton MRSI, which allows retrospective image-guided selection of spectra from very small brain volumes, is a technique that can be used to evaluate neuronal density in individual subcortical gray nuclei in the brains of patients with parkinsonism. Using this technique, we have shown that Parkinson's disease produces no change in relative levels of the neuronal marker, NAA, in the putamen. (C) 1997 Elsevier Science Inc.