title: Metabolic voxel-based analysis of the complete human brain using fast 3D-MRSI: Proof of concept in multiple sclerosis.
abstract: To detect local metabolic abnormalities over the complete human brain in multiple sclerosis (MS) patients, we used optimized fast volumic echo planar spectroscopic imaging (3D-EPSI).
  
  
  
  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 normalization, maps from 19 patients suffering from relapsing-remitting MS 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 gray matter (GM) atrophy maps were also generated.
  
  
  
  Two-group analysis of variance (ANOVA) (SPM8, P < 0.005, false discovery rate [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 1) 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; 2) increased m-Ins (around + 20%) inside WM T2 lesions and in the normal-appearing WM of temporal-occipital lobes, suggesting glial activation.
  
  
  
  We demonstrate the ability to noninvasively map 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. J. Magn. Reson. Imaging 2016;44:411-419.
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Donadieu
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Lecocq
authors.affiliation: Miller School of Medicine, University of Miami, Department of Radiology, Miami, Florida, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Maudsley
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.|AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Soraya
authors.initials: S
authors.lastname: Gherib
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Soulier
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.|AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Fanelly
authors.initials: F
authors.lastname: Pariollaud
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.|AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Ranjeva
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Guye
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle d'Imagerie, CEMEREM, Marseille, France.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Zaaraoui
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.|AP-HM, CHU Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Audoin
authors.affiliation: Aix Marseille Université, CNRS, CRMBM UMR 7339, Medical School of Marseille, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015588:Observer Variation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: inflammation; multiple sclerosis; neurodegeneration; proton magnetic resonance spectroscopic imaging; statistical mapping analysis; whole brain