Molality as a unit of measure for expressing 1H MRS brain metabolite concentrations in vivo

Absolute concentrations of cerebral metabolite in in vivo 1H magnetic resonance spectroscopy studies (1H-MRS) are widely reported in molar units as moles per liter of tissue, or in molal units as moles per kilogram of tissue. Such measurements require external referencing or assumptions as to local water content. To reduce the scan time, avoid assumptions that may be invalid under specific pathologies, and provide a universally accessible referencing procedure, we suggest that metabolite concentrations from 1H-MRS measurements in vivo be reported in molal units as moles per kilogram of tissue water. Using internal water referencing, a two-compartment water model, a simulated brain spectrum for peak identification, and a spectroscopic bi-exponential spin-spin relaxation segmentation technique, we measured the absolute concentrations for the four common 1H brain metabolites: choline (Cho), myo-inositol (mIno), phosphocreatine + creatine (Cr), and N-acetyl-aspartate (NAA), in the hippocampal region (n = 26) and along the Sylvian fissure (n = 61) of 35 healthy adults. A stimulated echo localization method (20 ms echo time, 10 ms mixing time, 4 s repetition time) yielded metabolite concentrations, uncorrected for metabolite relaxation or contributions from macromolecule resonances, that were expectantly higher than with molar literature values. Along the Sylvian fissure the average concentrations (coefficient of variation (CV)) in mmoles/kg of tissue water were 17.6 (12%) for NAA, 14.2 (9%) for Cr, 3.6 (13%) for Cho, and 13.2 (15%) for mIno. Respective values for the hippocampal region were 15.7 (20%), 14.7 (16%), 4.6 (19%), and 17.7 (26%). The concentrations of the two regions were significantly different (p