title: Metabolites predict lesion formation and severity in relapsing-remitting multiple sclerosis.
abstract: Multiple sclerosis is characterized by white matter lesions, which are visualized with conventional T2-weighted magnetic resonance imaging (MRI). Little is known about local metabolic processes preceding the appearance and during the pathological development of new lesions.
  
  
  
  To identify metabolite changes preceding white matter (WM) lesions and pathological severity of lesions over time.
  
  
  
  A total of 59 relapsing-remitting multiple sclerosis (MS) patients were scanned four times, with 6-month intervals. Imaging included short-TE magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI).
  
  
  
  A total of 16 new lesions appeared within the MRSI slab in 12 patients. Glutamate increased (+1.0 mM (+19%), p = 0.039) 12 and 6 months before new lesions appeared. In these areas, the increase in creatine and choline 6 months before until lesion appearance was negatively correlated with radial diffusivity (ρ = -0.73, p = 0.002 and ρ = -0.72, p = 0.002). Increase in creatine also correlated with the increase of axial diffusivity in the same period (ρ = -0.53, p = 0.034). When splitting the lesions into "mild" and "severe" based on radial diffusivity, only mild lesions showed an increase in creatine and choline during lesion formation ( p = 0.039 and p = 0.008, respectively).
  
  
  
  Increased glutamate heralded the appearance of new T2-visible WM lesions. In pathologically "mild" lesions, an increase in creatine and choline was found during lesion formation.
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology and Medical Informatics, University of Geneva, Switzerland.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Klauser
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Wiebenga
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Anand Jc
authors.initials: AJ
authors.lastname: Eijlers
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard Mj
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Physics and Medical Technology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Petra Jw
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jeroen Jg
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D002794:Choline / Q000378:metabolism; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology*; D055815:Young Adult
chemical_list: D018698:Glutamic Acid; D002794:Choline
keywords: DTI; MRI; MRS; MRSI; Multiple sclerosis; metabolite