Regional age-related effects in the monkey brain measured with 1H magnetic resonance spectroscopy

Abstract

The rhesus monkey is a useful model for examining age-related effects on the brain, because of the extensive neuroanatomical homology between the monkey and the human brain, the tight control for neurological diseases as well as the possibility of obtaining relevant behavioral data and post-mortem tissue for histological analyses. Here, proton magnetic resonance spectroscopy ((1)H-MRS) was used together with high-resolution anatomical MRI images to carefully assess regional concentrations of brain metabolites in a group of 20 rhesus monkeys. In an anterior volume of interest (VOI) that covered frontal and prefrontal areas, significant positive correlations of myo-inositol and of total creatine concentrations with age were detected, whereas N-acetyl aspartate (NAA) and choline compounds (Cho) were not significantly correlated with age. In an occipito-parietal VOI, all metabolites showed no statistically significant age-dependent trend. Strong correlations were found between NAA concentration and gray matter fraction in the VOIs as well as between choline compounds and white matter fraction.

Figure 1

Typical anterior VOI (panels a-c) and posterior VOI (panels d-f) in sagittal (a,d), coronal (b,e) and axial (c,f) views. Views are defined by the MRI coordinates and thus not parallel to the VOIs sides.

Figure 2

(a) coronal view of a skull-stripped T₁-weighted image. The contours of the anterior VOI are marked in dashed gray line; (b) segmentation results of the same slice. Dark gray: CSF, light gray: gray matter, white: white matter; (c) same slice - gray matter probability map; (d) white matter probability map; (e) CSF probability map; (f) intersection between the gray matter probability map and the VOI.

Figure 3

Tissue fractions in (a) the anterior VOI and (b) the posterior VOI against age. GM: gray matter, WM: white matter, CSF: cerebrospinal fluid.

Figure 4

Typical anterior VOI MRS spectra taken from (a) a 8.4 year old and (b) a 24.4 year old monkey. The actual concentrations in i.u. for the spectrum in (a) are: NAA=9.15 i.u., Cho=1.67 i.u., tCr=11.16 i.u., MI=6.60 i.u., and for the spectrum in (b): NAA=9.04 i.u., Cho=1.47 i.u., tCR=12.98 i.u. and MI=9.3 i.u.

Figure 5

Metabolite concentrations vs. age in the anterior VOI (panels a,b) and in the posterior VOI (panels c,d). Concentrations are given in institutional units (i.u.). MI and tCr in the anterior VOI showed significant positive correlation with age, and NAA in the posterior VOI exhibited a less-than-significant negative trend.

Figure 6

Metabolite concentrations vs. gray matter fraction, f(GM), for all measurements. The metabolites that showed the most significant correlation with tissue type were NAA, which positively correlated with f(GM) and Cho, which negatively correlated with f(GM) and positively with the white matter fraction. tCr and MI were not significantly correlated with either tissue type.