Skip to main content Accessibility help
  • Print publication year: 2009
  • Online publication date: August 2010

4 - Normal regional variations: brain development and aging


Key points

Substantial regional variations in proton brain spectra exist; differences between gray and white matter, anterior–posterior gradients, and differences between the supra- and infra-tentorial brain are common.

Spectra change rapidly over the first few years of life; at birth, NAA is low, and choline and myo-inositol are high. By about 4 years of age, spectra from most regions have a more “adult-like” appearance.

In normal development, only subtle age-related changes are found between the ages of 4 and 20 years.

In normal aging, only subtle age-related changes are found. A recent meta-analysis indicated the most common findings are mildly increased choline and creatine in frontal brain regions of elderly subjects (> 68 years), and stable or slightly decreasing (parietal regions only) NAA.


Interpretation of spectra from patients with neuropathology requires a knowledge of the normal regional and age-related spectral variations seen in the healthy brain. This is a difficult issue, since spectra are quite dependent on the technique used to record them (particularly choice of echo time, and field strength), and also show quite large regional and age-related (at least in young children) dependencies. However, while there still remain some gaps in the literature (e.g. detailed, regional studies in very young children), for the most part regional and age-related changes in brain spectra are now well-characterized. This chapter reviews what is known about regional metabolite variations, as well as metabolic changes associated with brain development, and aging.

Hetherington, HP, Mason, GF, Pan, JW, Ponder, SL, Vaughan, JT, Twieg, DB, et al. Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1 T. Magn Reson Med 1994; 32: 565–71.
Kreis, R, Ernst, T, Ross, BD. Absolute quantitation of water and metabolites in the human brain. II. Metabolite concentrations. J Magn Reson Ser B 1993; 102: 9–19.
Michaelis, T, Merboldt, KD, Bruhn, H, Hanicke, W, Frahm, J. Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology 1993; 187: 219–27.
Soher, BJ, Zijl, PC, Duyn, JH, Barker, PB. Quantitative proton MR spectroscopic imaging of the human brain. Magn Reson Med 1996; 35: 356–63.
Degaonkar, MN, Pomper, MG, Barker, PB. Quantitative proton magnetic resonance spectroscopic imaging: regional variations in the corpus callosum and cortical gray matter. J Magn Reson Imaging 2005; 22: 175–9.
Pouwels, PJ, Frahm, J. Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med 1998; 39: 53–60.
Barker, PB, Szopinski, K, Horska, A. Metabolic heterogeneity at the level of the anterior and posterior commissures. Magn Reson Med 2000; 43: 348–54.
Jacobs, MA, Horska, A, Zijl, PC, Barker, PB. Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain stem. Magn Reson Med 2001; 46: 699–705.
Breiter, SN, Arroyo, S, Mathews, VP, Lesser, RP, Bryan, RN, Barker, PB. Proton MR spectroscopy in patients with seizure disorders. Am J Neuroradiol 1994; 15: 373–84.
Vermathen, P, Laxer, KD, Matson, GB, Weiner, MW. Hippocampal structures: anteroposterior N-acetylaspartate differences in patients with epilepsy and control subjects as shown with proton MR spectroscopic imaging. Radiology 2000; 214: 403–10.
Arslanoglu, A, Bonekamp, D, Barker, PB, Horska, A. Quantitative proton MR spectroscopic imaging of the mesial temporal lobe. J Magn Reson Imaging 2004; 20: 772–8.
Charles, HC, Lazeyras, F, Krishnan, KRR, Boyko, OB, Patterson, LJ, Doraiswamy, PM, et al. Proton spectroscopy of human brain: effects of age and sex. Prog Neuro-Psychopharmacol Biol Psychiat 1994; 18: 995.
Nagae-Poetscher, LM, Bonekamp, D, Barker, PB, Brant, LJ, Kaufmann, WE, Horska, A. Asymmetry and gender effect in functionally lateralized cortical regions: a proton MRS imaging study. J Magn Reson Imaging 2004; 19: 27–33.
Baker, EH, Basso, G, Barker, PB, Smith, MA, Bonekamp, D, Horska, A. Regional apparent metabolite concentrations in young adult brain measured by (1)H MR spectroscopy at 3 Tesla. J Magn Reson Imaging 2008; 27: 489–99.
Huppi, PS, Posse, S, Lazeyras, F, Burri, R, Bossi, E, Herschkowitz, N. Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing brain. Pediatric Res 1991; 30: 574–8.
Kimura, H, Fujii, Y, Itoh, S, Matsuda, T, Iwasaki, T, Maeda, M, et al. Metabolic alterations in the neonate and infant brain during development: evaluation with proton MR spectroscopy. Radiology 1995; 194: 483–9.
Kreis, R, Ernst, T, Ross, BD. Development of the human brain: in vivo quantification of metabolite and water content with proton magnetic resonance spectroscopy. Magn Reson Med 1993; 30: 424–37.
Knaap, MS, Grond, J, Rijen, PC, Faber, JA J, Valk, J, Willemse, K. Age-dependent changes in localized proton and phosphorus MR spectrscopy of the brain. Radiology 1990; 176: 509–15.
Pouwels, PJ, Brockmann, K, Kruse, B, Wilken, B, Wick, M, Hanefeld, F, et al. Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatr Res 1999; 46: 474–85.
Horska, A, Kaufmann, WE, Brant, LJ, Naidu, S, Harris, JC, Barker, PB. In vivo quantitative proton MRSI study of brain development from childhood to adolescence. J Magn Reson Imaging 2002; 15: 137–43.
Christiansen, P, Toft, P, Larsson, HB W, Stubgaard, M, Henriksen, O. The concentration of N-acetyl aspartate, creatine+phosphocreatine, and choline in different parts of the brain in adulthood and senium. Magn Reson Imaging 1993; 11: 799.
Lim, KO, Spielman, DM. Estimating NAA in cortical gray matter with applications for measuring changes due to aging. Magn Reson Med 1997; 37: 372–7.
Chang, L, Ernst, T, Poland, RE, Jenden, DJ. In vivo proton magnetic resonance spectroscopy of the normal aging human brain. Life Sci 1996; 58: 2049.
Lundbom, N, Barnett, A, Bonavita, S, Patronas, N, Rajapakse, J, Tedeschi, Di Chiro G. MR image segmentation and tissue metabolite contrast in 1H spectroscopic imaging of normal and aging brain. Magn Reson Med 1999; 41: 841–5.
Haga, KK, Khor, YP, Farrall, A, Wardlaw, JM. A systematic review of brain metabolite changes, measured with (1)H magnetic resonance spectroscopy, in healthy aging. Neurobiol Aging 2009; 30: 353–63.
Maudsley, AA, Darkazanli, A, Alger, JR, Hall, LO, Schuff, N, Studholme, C, et al. Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging. NMR Biomed 2006; 19: 492–503.
Kaiser, LG, Schuff, N, Cashdollar, N, Weiner, MW. Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T. Neurobiol Aging 2005; 26: 665–72.
Mascalchi, M, Brugnoli, R, Guerrini, L, Belli, G, Nistri, M, Politi, LS, et al. Single-voxel long TE 1H-MR spectroscopy of the normal brainstem and cerebellum. J Magn Reson Imaging 2002; 16: 532–7.