Regional Metabolite Concentrations in Aging Human Brain: Comparison of Short-TE Whole Brain MR Spectroscopic Imaging and Single Voxel Spectroscopy at 3T

  • Helen Maghsudi
  • Birte Schmitz
  • Andrew A. Maudsley
  • Sulaiman Sheriff
  • Paul Bronzlik
  • Martin Schütze
  • Heinrich Lanfermann
  • Xiaoqi DingEmail author
Original Article



The aim of this study was to compare a recently established whole brain MR spectroscopic imaging (wbMRSI) technique using spin-echo planar spectroscopic imaging (EPSI) acquisition and the Metabolic Imaging and Data Analysis System (MIDAS) software package with single voxel spectroscopy (SVS) technique and LCModel analysis for determination of relative metabolite concentrations in aging human brain.


A total of 59 healthy subjects aged 20–70 years (n ≥ 5 per age decade for each gender) underwent a wbEPSI scan and 3 SVS scans of a 4 ml voxel volume located in the right basal ganglia, occipital grey matter and parietal white matter. Concentration ratios to total creatine (tCr) for N‑acetylaspartate (NAA/tCr), total choline (tCho/tCr), glutamine (Gln/tCr), glutamate (Glu/tCr) and myoinositol (mI/tCr) were obtained both from EPSI and SVS acquisitions with either LCModel or MIDAS. In addition, an aqueous phantom containing known metabolite concentrations was also measured.


Metabolite concentrations obtained with wbMRSI and SVS were comparable and consistent with those reported previously. Decreases of NAA/tCr and increases of line width with age were found with both techniques, while the results obtained from EPSI acquisition revealed generally narrower line widths and smaller Cramer-Rao lower bounds than those from SVS data.


The wbMRSI could be used to estimate metabolites in vivo and in vitro with the same reliability as using SVS, with the main advantage being the ability to determine metabolite concentrations in multiple brain structure simultaneously in vivo. It is expected to be widely used in clinical diagnostics and neuroscience.


Spin-echo planar spectroscopic imaging Metabolic Imaging and Data Analysis System Aging 



We would like to thank the research volunteers.


This work was partially supported by the Deutsche Forschungsgemeinschaft. Additional support was provided under NIH grant R01 EB016064 (AAM).

Conflict of interest

H. Maghsudi, B. Schmitz, A.A. Maudsley, S. Sheriff, P. Bronzlik, M. Schütze, H. Lanfermann and X. Ding declare that they have no competing interests.


  1. 1.
    Ding XQ, Maudsley AA, Sabati M, Sheriff S, Schmitz B, Schütze M, Bronzlik P, Kahl KG, Lanfermann H. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging. Neuroimage. 2016;137:45–51.CrossRefGoogle Scholar
  2. 2.
    Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC. Brain metabolism differs in Alzheimer’s disease and Parkinson’s disease dementia. Alzheimers Dement. 2008;4:421–7.CrossRefGoogle Scholar
  3. 3.
    Hall H, Cuellar-Baena S, Dahlberg C, In’t Zandt R, Denisov V, Kirik D. Magnetic resonance spectroscopic methods for the assessment of metabolic functions in the diseased brain. Curr Top Behav Neurosci. 2012;11:169–98.CrossRefGoogle Scholar
  4. 4.
    Frahm J, Bruhn H, Gyngell ML, Merboldt KD, Hänicke W, Sauter R. Localized high-resolution proton NMR spectroscopy using stimulated echoes: initial applications to human brain in vivo. Magn Reson Med. 1989;9:79–93.CrossRefGoogle Scholar
  5. 5.
    Naressi A, Couturier C, Devos JM, Janssen M, Mangeat C, de Beer R, Graveron-Demilly D. Java-based graphical user interface for the MRUI quantitation package. MAGMA. 2001;12:141–52.CrossRefGoogle Scholar
  6. 6.
    Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30:672–9.CrossRefGoogle Scholar
  7. 7.
    Sabati M, Sheriff S, Gu M, Wei J, Zhu H, Barker PB, Spielman DM, Alger JR, Maudsley AA. Multivendor implementation and comparison of volumetric whole-brain echo-planar MR spectroscopic imaging. Magn Reson Med. 2015;74:1209–20.CrossRefGoogle Scholar
  8. 8.
    Ding XQ, Lanfermann H. Whole brain (1)H-spectroscopy: a developing technique for advanced analysis of cerebral metabolism. Clin Neuroradiol. 2015;25(Suppl 2):245–50.CrossRefGoogle Scholar
  9. 9.
    Maudsley AA, Govind V, Arheart KL. Associations of age, gender and body mass with 1H MR-observed brain metabolites and tissue distributions. NMR Biomed. 2012;25:580–93.CrossRefGoogle Scholar
  10. 10.
    Eylers VV, Maudsley AA, Bronzlik P, Dellani PR, Lanfermann H, Ding XQ. Detection of normal aging effects on human brain metabolite concentrations and microstructure with whole-brain MR spectroscopic imaging and quantitative MR imaging. AJNR Am J Neuroradiol. 2016;37:447–54.CrossRefGoogle Scholar
  11. 11.
    Ding XQ, Maudsley AA, Sabati M, Sheriff S, Dellani PR, Lanfermann H. Reproducibility and reliability of short-TE whole-brain MR spectroscopic imaging of human brain at 3T. Magn Reson Med. 2015;73:921–8.CrossRefGoogle Scholar
  12. 12.
    Zhang Y, Taub E, Salibi N, Uswatte G, Maudsley AA, Sheriff S, Womble B, Mark VW, Knight DC. Comparison of reproducibility of single voxel spectroscopy and whole-brain magnetic resonance spectroscopy imaging at 3T. NMR Biomed. 2018;31:e3898.Google Scholar
  13. 13.
    Maudsley AA, Darkazanli A, Alger JR, Hall LO, Schuff N, Studholme C, Yu Y, Ebel A, Frew A, Goldgof D, Gu Y, Pagare R, Rousseau F, Sivasankaran K, Soher BJ, Weber P, Young K, Zhu X. Comprehensive processing, display and analysis for in vivo MR spectroscopic imaging. NMR Biomed. 2006;19:492–503.CrossRefGoogle Scholar
  14. 14.
    Maudsley AA, Domenig C, Govind V, Darkazanli A, Studholme C, Arheart K, Bloomer C. Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI). Magn Reson Med. 2009;61:548–59.CrossRefGoogle Scholar
  15. 15.
    Steer RA, Clark DA, Beck AT, Ranieri WF. Common and specific dimensions of self-reported anxiety and depression: the BDI-II versus the BDI-IA. Behav Res Ther. 1999;37:183–90.CrossRefGoogle Scholar
  16. 16.
    Kalbe E, Kessler J, Calabrese P, Smith R, Passmore AP, Brand M, Bullock R. DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia. Int J Geriatr Psychiatry. 2004;19:136–43.CrossRefGoogle Scholar
  17. 17.
    Haupt CI, Schuff N, Weiner MW, Maudsley AA. Removal of lipid artifacts in 1H spectroscopic imaging by data extrapolation. Magn Reson Med. 1996;35:678–87.CrossRefGoogle Scholar
  18. 18.
    Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23(Suppl 1):S208–19.CrossRefGoogle Scholar
  19. 19.
    Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 2001;20:45–57.CrossRefGoogle Scholar
  20. 20.
    Goryawala MZ, Sheriff S, Maudsley AA. Regional distributions of brain glutamate and glutamine in normal subjects. NMR Biomed. 2016;29:1108–16.CrossRefGoogle Scholar
  21. 21.
    Ebel A, Maudsley AA. Improved spectral quality for 3D MR spectroscopic imaging using a high spatial resolution acquisition strategy. Magn Reson Imaging. 2003;21:113–20.CrossRefGoogle Scholar
  22. 22.
    Grachev ID, Apkarian AV. Chemical heterogeneity of the living human brain: a proton MR spectroscopy study on the effects of sex, age, and brain region. Neuroimage. 2000;11(5 Pt 1):554–63.CrossRefGoogle Scholar
  23. 23.
    Pouwels PJ, Brockmann K, Kruse B, Wilken B, Wick M, Hanefeld F, Frahm J. Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS. Pediatr Res. 1999;46:474–85.CrossRefGoogle Scholar
  24. 24.
    Natt O, Bezkorovaynyy V, Michaelis T, Frahm J. Use of phased array coils for a determination of absolute metabolite concentrations. Magn Reson Med. 2005;53:3–8.CrossRefGoogle Scholar
  25. 25.
    Boelmans K, Holst B, Hackius M, Finsterbusch J, Gerloff C, Fiehler J, Münchau A. Brain iron deposition fingerprints in Parkinson’s disease and progressive supranuclear palsy. Mov Disord. 2012;27:421–7.CrossRefGoogle Scholar
  26. 26.
    Kirov II, Fleysher L, Fleysher R, Patil V, Liu S, Gonen O. Age dependence of regional proton metabolites T2 relaxation times in the human brain at 3 T. Magn Reson Med. 2008;60:790–5.CrossRefGoogle Scholar
  27. 27.
    Marjanska M, Emir UE, Deelchand DK, Terpstra M. Faster metabolite (1)H transverse relaxation in the elder human brain. PLoS ONE. 2013;8:e77572.CrossRefGoogle Scholar
  28. 28.
    Mitsumori F, Watanabe H, Takaya N. Estimation of brain iron concentration in vivo using a linear relationship between regional iron and apparent transverse relaxation rate of the tissue water at 4.7T. Magn Reson Med. 2009;62:1326–30.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Diagnostic and Interventional NeuroradiologyHannover Medical SchoolHannoverGermany
  2. 2.Department of RadiologyUniversity of Miami School of MedicineMiamiUSA

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