title: Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy.
abstract: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS).
  
  
  
  Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations.
  
  
  
  In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores.
  
  
  
  DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France/AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/Centre de NeuroImagerie de Recherche - Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Branzoli
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Poirion
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: García-Lorenzo
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/Centre de NeuroImagerie de Recherche - Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Didier
authors.affiliation: AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maillart
authors.affiliation: AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Socha
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Bera
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Itamar
authors.initials: I
authors.lastname: Ronen
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/Centre de NeuroImagerie de Recherche - Institut du Cerveau et de la Moelle épinière (ICM), Paris, France/AP-HP, Hôpital de la Pitié Salpêtrière, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lehericy
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR 7225, INSERM, Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Hôpital de la Pitié Salpêtrière, Paris, France/AP-HP, Hôpital Saint-Antoine, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001284:Atrophy / Q000473:pathology; D003401:Creatine / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology
chemical_list: D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine
keywords: Multiple sclerosis; diffusion-weighted spectroscopy; energy dysregulation