title: Normal appearing and diffusely abnormal white matter in patients with multiple sclerosis assessed with quantitative MR.
abstract: BACKGROUND
  Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both 'normal appearing white matter' (NAWM) and 'diffusely abnormal white matter' (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes. In this study, qMRI and qMRS were used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to 'normal white matter' (NWM) in healthy controls.
  
  
  METHODS
  QMRI and qMRS measurements were performed on a 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the 'Barkhof-Tintoré criteria' for MS, ('MRIpos'), whereas 15 showed radiologically atypical findings with few WM lesions ('MRIneg'). QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS.
  
  
  RESULTS
  NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF.
  
  
  CONCLUSIONS
  Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox.
authors.affiliation: Radiation Physics, Department of Medicine and Health, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: West
authors.affiliation: Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Radiological Sciences, Department of Medicine and Health, Linköping University, Department of Radiation Physics, UHL County Council of Östergötland, Linköping, Sweden.
authors.forename: Anne
authors.initials: A
authors.lastname: Aalto
authors.affiliation: Radiation Physics, Department of Medicine and Health, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Tisell
authors.affiliation: Radiation Physics, Department of Medicine and Health, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
authors.forename: Olof Dahlqvist
authors.initials: OD
authors.lastname: Leinhard
authors.affiliation: Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Department of Neurology, Linköping University, and Neurology, UHL and LiM County Council of Östergötland, Linköping, Sweden.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Landtblom
authors.affiliation: Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Radiology, Department of Medicine and Health, Linköping University, Department of Radiology, UHL County Council of Östergötland, Linköping, Sweden.
authors.forename: Örjan
authors.initials: Ö
authors.lastname: Smedby
authors.affiliation: Radiation Physics, Department of Medicine and Health, Linköping University, Linköping, Sweden; Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden; Radiological Sciences, Department of Medicine and Health, Linköping University, Department of Radiation Physics, UHL County Council of Östergötland, Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
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