Cross-sectional and longitudinal reproducibility of rhesus macaque brain metabolites: a proton MR spectroscopy study at 3 T

Non-human primates are often used as preclinical model systems for (mostly diffuse or multi-focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non-destructive imaging modalities, MRI and proton MR spectroscopy ((1) H MRS). Cost may explain why the inter- and intra-animal reproducibility of the (1) H MRS observed brain metabolites, are not reported. To this end, we performed test-retest three-dimensional brain (1) H MRS in five healthy rhesus macaques at 3 T. Spectra were acquired from 224 isotropic (0.5 cm)(3) = 125 μL voxels, over 28 cm(3) (∼ 35%) of the brain, then individually phased, frequency aligned and summed into a spectrum representative of the entire volume of interest. This dramatically increases the metabolites' signal-to-noise ratios, while maintaining the (narrow) voxel linewidth. The results show that the average N-acetylaspartate, creatine, choline, and myo-inositol concentrations in the macaque brain are: 7.7 ± 0.5, 7.0 ± 0.5, 1.2 ± 0.1 and 4.0 ± 0.6 mM/g wet weight (mean ± standard deviation). Their inter-animal coefficients of variation (CV) are 4%, 4%, 6%, and 15%; and the longitudinal (intra-animal) CVs are lower still: 4%, 5%, 5%, and 4%, much better than the 22%, 33%, 36%, and 45% intra-voxel CVs, demonstrating the advantage of the approach and its utility for preclinical studies of diffuse neurological diseases in rhesus macaques.