title: On the computational assessment of white matter hyperintensity progression: difficulties in method selection and bias field correction performance on images with significant white matter pathology.
abstract: BACKGROUND
  Subtle inhomogeneities in the scanner's magnetic fields (B0 and B1) alter the intensity levels of the structural magnetic resonance imaging (MRI) affecting the volumetric assessment of WMH changes. Here, we investigate the influence that (1) correcting the images for the B1 inhomogeneities (i.e. bias field correction (BFC)) and (2) selection of the WMH change assessment method can have on longitudinal analyses of WMH progression and discuss possible solutions.
  
  
  METHODS
  We used brain structural MRI from 46 mild stroke patients scanned at stroke onset and 3 years later. We tested three BFC approaches: FSL-FAST, N4 and exponentially entropy-driven homomorphic unsharp masking (E(2)D-HUM) and analysed their effect on the measured WMH change. Separately, we tested two methods to assess WMH changes: measuring WMH volumes independently at both time points semi-automatically (MCMxxxVI) and subtracting intensity-normalised FLAIR images at both time points following image gamma correction. We then combined the BFC with the computational method that performed best across the whole sample to assess WMH changes.
  
  
  RESULTS
  Analysis of the difference in the variance-to-mean intensity ratio in normal tissue between BFC and uncorrected images and visual inspection showed that all BFC methods altered the WMH appearance and distribution, but FSL-FAST in general performed more consistently across the sample and MRI modalities. The WMH volume change over 3 years obtained with MCMxxxVI with vs. without FSL-FAST BFC did not significantly differ (medians(IQR)(with BFC) = 3.2(6.3) vs. 2.9(7.4)ml (without BFC), p = 0.5), but both differed significantly from the WMH volume change obtained from subtracting post-processed FLAIR images (without BFC)(7.6(8.2)ml, p < 0.001). This latter method considerably inflated the WMH volume change as subtle WMH at baseline that became more intense at follow-up were counted as increase in the volumetric change.
  
  
  CONCLUSIONS
  Measurement of WMH volume change remains challenging. Although the overall volumetric change was not significantly affected by the application of BFC, these methods distorted the image intensity distribution affecting subtle WMH. Subtracting the FLAIR images at both time points following gamma correction seems a promising technique but is adversely affected by subtle WMH. It is important to take into account not only the changes in volume but also in the signal intensity.
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. mvhernan@staffmail.ed.ac.uk.
authors.forename: Maria Del C
authors.initials: Mdel C
authors.lastname: Valdés Hernández
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Victor
authors.initials: V
authors.lastname: González-Castro
authors.affiliation: College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Dina T
authors.initials: DT
authors.lastname: Ghandour
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Fergus
authors.initials: F
authors.lastname: Doubal
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Muñoz Maniega
authors.affiliation: Department of Cardiovascular Sciences, University of Sheffield, Sheffield, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Armitage
authors.affiliation: Department of Neuroimaging Sciences, Centre for Clinical Brian Sciences, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D020521:Stroke / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: Cerebrovascular disorders; Leukoencephalopathies; MRI; Neuroimaging; White matter hyperintensities
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