Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy

Magn Reson Imaging. 2003 Oct;21(8):923-8. doi: 10.1016/s0730-725x(03)00181-4.


In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are often expressed as ratios, rather than as absolute concentrations. Frequently, their denominator is the creatine [Cr], which level is explicitly assumed to be stable in normal as well as in many pathologic states. The rationale is that ratios self-correct for imager and localization method differences, gain instabilities, regional susceptibility variations and partial volume effects. The implicit assumption is that these benefits are worth their cost(w)-(w) propagation of the individual variation of each of the ratio's components. To test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho] and [Cr] were quantified in various regions of the brains of 8 volunteers, using 3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore, in approximately 33% of these voxels, the ratios' CVs exceeded even the combined constituents' CVs. Consequently, basing metabolite quantification on ratios and assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents. Therefore, its cost exceeds the benefit.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / analysis
  • Brain Chemistry*
  • Choline / analysis
  • Creatine / analysis*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Imaging, Three-Dimensional
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged


  • Aspartic Acid
  • N-acetylaspartate
  • Creatine
  • Choline