title: Cross-sectional and longitudinal reproducibility of rhesus macaque brain metabolites: a proton MR spectroscopy study at 3 T.
abstract: 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.
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Wu
authors.forename: Ivan I
authors.initials: II
authors.lastname: Kirov
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.forename: Chan-Gyu
authors.initials: CG
authors.lastname: Joo
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ratai
authors.forename: R Gilberto
authors.initials: RG
authors.lastname: González
authors.forename: Oded
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007294:Inositol / Q000378:metabolism; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D023421:Models, Animal; D015203:Reproducibility of Results
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline