Purpose To improve the extent over which whole brain quantitative 3D-MRSI maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. Materials and Methods Two short TE (20 ms) acquisitions of 3D Echo Planar Spectroscopic Imaging at two orientations, one in the anterior commissure – posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3T in a group of ten healthy volunteers. B1+, B1−, and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. Results The combined metabolite maps derived from the two acquisitions reduced the regional inter-subject variance. The numbers of AAL regions showing NAA SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions out of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA=10.03+1.71, cCho=1.78±0.55, cCr=7.29±1.69; cmIns=5.30±2.67) and in cerebellum (cNAA=5.28±1.77, cCho=1.60±0.41, cCr=6.95±2.15; cmIns=3.60±0.74). Conclusion A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain.

Purpose Using optimized fast volumic echo planar spectroscopic imaging (3D-EPSI), we aimed to detect local metabolic abnormalities over the complete human brain in multiple sclerosis patients. Materials and methods Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins) and creatine+phosphocreatine (tCr). After spatial normalisation, maps from 19 patients suffering from relapsing-remitting multiple sclerosis were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and grey matter (GM) atrophy maps were also generated. Results Two-group ANOVA (SPM8, p<0.005, FDR corrected p<0.05 at the cluster level with age and sex as confounding covariates) comparing Patients and controls matched for age and sex showed clusters of abnormal metabolite levels with i) decreased NAA (around −15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction, ii) increased m-Ins (around +20%) inside WM T2 lesions and in the normal appearing WM of temporal-occipital lobes suggesting glial activation. Conclusion We demonstrated the ability to map non-invasively over the complete brain - from vertex to cerebellum – with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact.