Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS

Regional changes of metabolite concentrations during human brain developmen t were assessed by quantitative localized proton magnetic resonance spectro scopy in vivo. Apart from measurements in young healthy adults, the study w as based on regional spectra from 97 children who were either healthy or su ffered from mental retardation, movement disorders, epilepsies, neoplasm, o r vascular malformation. Metabolite quantitation focused on cortical gray a nd white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood the concentration o f the neuroaxonally located N-acetylaspartate increased in gray matter, cer ebellum, and thalamus, whereas a constant level was detected in white matte r. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acet ylaspartate as a marker of functioning neuroaxonal tissue rather than of th e mere presence of nerve cells. This view is further supported by high conc entrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formatio n. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain c onstant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in th alamus and white matter, and a decrease of glutamine in white matter. Despi te regional differences and some small changes during the first year of lif e, the concentrations of creatine, phosphocreatine, choline-containing comp ounds, myoinositol, and glutamate remain constant afterward. The creatine t o phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonan ce line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.