title: Grey Matter Atrophy in Multiple Sclerosis: Clinical Interpretation Depends on Choice of Analysis Method.
abstract: BACKGROUND
  Studies disagree on the location of grey matter (GM) atrophy in the multiple sclerosis (MS) brain.
  
  
  OBJECTIVE
  To examine the consistency between FSL, FreeSurfer, SPM for GM atrophy measurement (for volumes, patient/control discrimination, and correlations with cognition).
  
  
  METHODS
  127 MS patients and 50 controls were included and cortical and deep grey matter (DGM) volumetrics were performed. Consistency of volumes was assessed with Intraclass Correlation Coefficient/ICC. Consistency of patients/controls discrimination was assessed with Cohen's d, t-tests, MANOVA and a penalized double-loop logistic classifier. Consistency of association with cognition was assessed with Pearson correlation coefficient and ANOVA. Voxel-based morphometry (SPM-VBM and FSL-VBM) and vertex-wise FreeSurfer were used for group-level comparisons.
  
  
  RESULTS
  The highest volumetry ICC were between SPM and FreeSurfer for cortical regions, and the lowest between SPM and FreeSurfer for DGM. The caudate nucleus and temporal lobes had high consistency between all software, while amygdala had lowest volumetric consistency. Consistency of patients/controls discrimination was largest in the DGM for all software, especially for thalamus and pallidum. The penalized double-loop logistic classifier most often selected the thalamus, pallidum and amygdala for all software. FSL yielded the largest number of significant correlations. DGM yielded stronger correlations with cognition than cortical volumes. Bilateral putamen and left insula volumes correlated with cognition using all methods.
  
  
  CONCLUSIONS
  GM volumes from FreeSurfer, FSL and SPM are different, especially for cortical regions. While group-level separation between MS and controls is comparable, correlations between regional GM volumes and clinical/cognitive variables in MS should be cautiously interpreted.
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Veronica
authors.initials: V
authors.lastname: Popescu
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Menno M
authors.initials: MM
authors.lastname: Schoonheim
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Versteeg
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nimisha
authors.initials: N
authors.lastname: Chaturvedi
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Jonker
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Renee
authors.initials: R
authors.lastname: Xavier de Menezes
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Francisca
authors.initials: F
authors.lastname: Gallindo Garre
authors.affiliation: Department of Neurology, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.|Department of Physics and Medical Technology, Neuroscience Campus Amsterdam (NCA), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011859:Radiography