title: Accurate GM atrophy quantification in MS using lesion-filling with co-registered 2D lesion masks.
abstract: BACKGROUND
  In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require precise lesion identification on 3DT1-images.
  
  
  OBJECTIVE
  To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks.
  
  
  METHODS
  2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests.
  
  
  RESULTS
  Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST.
  
  
  CONCLUSIONS
  These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Popescu
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: N C G
authors.initials: NC
authors.lastname: Ran
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK ; National Institute for Health Research (NIHR), University College London Hospitals (UCLH), Biomedical Research Centre, London, UK.
authors.forename: D T
authors.initials: DT
authors.lastname: Chard
authors.affiliation: NMR Research Unit, Queen Square Multiple Sclerosis Centre, University College London (UCL) Institute of Neurology, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands ; Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Vrenken
mesh_terms: D000328:Adult; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; 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*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009929:Organ Size; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique; D066127:White Matter / Q000473:pathology*
keywords: FSL; LEAP; Lesion filling; Multiple sclerosis