Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain

S. F. Keevil, B. Barbiroli, J. C W Brooks, E. B. Cady, R. Canese, P. Carlier, D. J. Collins, P. Gilligan, G. Gobbi, J. Hennig, H. Kügel, M. O. Leach, D. Metzler, V. Mlynárik, E. Moser, M. C. Newbold, G. S. Payne, P. Ring, J. N. Roberts, I. J. RowlandT. Thiel, I. Tkác, S. Topp, H. J. Wittsack, M. Wylezinska, P. Zaniol, O. Henriksen, F. Podo

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We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean ± SD): [NAA] = 10.0 ± 3.4 mM (n = 53), [tCho] = 1.9 ± 1.0 mM (n = 51), [Cr + PCr] = 6.5 ± 3.7 mM (n = 51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

Original languageEnglish (US)
Pages (from-to)1093-1106
Number of pages14
JournalMagnetic Resonance Imaging
Issue number9
StatePublished - Nov 1998

Bibliographical note

Funding Information:
The authors gratefully acknowledge the financial support of the Commission of the European Communities (BIOMED 1 contract PL920432). D. Metzler was supported by the Austrian Ministry of Science (grant GZ 140.019/2-Pr/4/95), and M.C. Newbold by the Special Trustees of Guy’s Hospital (MB PhD award).


  • Absolute quantification in MRS
  • Human brain
  • Instrumental calibration
  • Test objects


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