Quantifying metabolite ratios and concentrations by Non-1H MRS

Practical noninvasive methods for the measurement of absolute concentrations are critical for assessing depletion of metabolite pools in healthy and diseased heart, brain, and other organs. Magnetic resonance spectroscopy (MRS) offers unique noninvasive access to many metabolites, but the reproducibility of metabolite measurements is often confounded by nuclear magnetic resonance (NMR) relaxation, nonuniform excitation and sensitivity, and partial volume effects in the typically large and often poorly defined voxels that are commonly used for localized MRS with nonhydrogen (¹H) nuclei. Here, practical acquisition and analysis protocols are presented for the quantification of endogenous metabolite ratios and concentrations using non-¹H MRS. Starting with the theoretical basis that links NMR signal and concentration, methods of measuring relative metabolite ratios with corrections for T ₁ and T ₂ relaxation, nonuniform excitation, and partial volume effects are examined. This is extended to absolute concentration measurements using an internal concentration reference or metabolite 'candle'; using a homonuclear concentration reference located either within the field-of-view of the MRS exam or measured in a separate calibration study; and heteronuclear concentration referencing based on the ¹H MRS tissue water signal as the reference. MRS-based methods of partial volume correction that employ spectral markers, and those based on MRI tissue segmentation with intravoxel sensitivity weighting, are also presented. Finally, five protocols for measuring metabolite ratios and concentrations in the human heart and the brain at 1.5 and 3 T with ³¹P MRS are exemplified.