The in vivo neuronal contribution to human cerebral metabolic rate of glucose (CMRglc), measured by 18FDG-PET, is unknown. Examining the effect of 1H MRSI-derived N-acetyl aspartate (NAA) concentration on positron emission tomography (PET) measures of metabolic activity might indicate the relationship of CMRglc to neuron density. In a population of 19 demented, cognitively impaired, and control subjects, the Miller-Gartner algorithm was applied to whole-brain PET data to isolate the PET signal originating in cortical gray matter alone (GMPET). An analogous procedure applied to multislice proton MRSI data yielded the N-acetyl aspartate concentration in cortical gray matter (GMNAA). In 18 of 19 subjects, a significant linear regression (P < 0.05) resulted when GMPET was plotted against GMNAA, whereby GMPET was higher for higher GMNAA. This suggests that CMRglc rises linearly with increasing neuron density in gray matter. This method may be used to investigate the relationship of CMRglc to neurons in various conditions.