title: Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis.
abstract: OBJECTIVE
  MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18).
  
  
  METHODS
  An automated tissue segmentation protocol that was optimized for an elderly population, a brain regional parcellation procedure, and a lesion segmentation protocol were applied to measure tissue volumes (whole brain and regional lobar volumes) with and without lesion segmentation to quantify the volume of misclassified tissue.
  
  
  RESULTS
  After application of the tissue segmentation protocol and lesion analysis, mean total percentage misclassified volume across all subjects was 2% (17.9 cm(3)) of whole brain volume (corrected for total intracranial capacity). Mean percentage of misclassified tissue volumes for the severe group was 4.8% of whole brain, which translates to a mean volume 42.2 cm(3). Gray matter volume was most overestimated in the severe group, where 6.4% of the total gray matter volume was derived from misclassified WMH. The regional analysis showed that frontal (41%, 7.4 cm(3)) and inferior parietal (18%, 3.25 cm(3)) lobes were most affected by tissue misclassification.
  
  
  CONCLUSIONS
  MRI-based volumetric studies of Alzheimer Disease that do not account for WMH can expect an erroneous inflation of gray or white matter volumes, especially in the frontal and inferior parietal regions. To avoid this source of error, MRI-based volumetric studies in patient populations susceptible to hyperintensities should include a WMH segmentation protocol.
authors.affiliation: L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. naama.levy@sunnybrook.ca
authors.forename: Naama
authors.initials: N
authors.lastname: Levy-Cooperman
authors.forename: Joel
authors.initials: J
authors.lastname: Ramirez
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lobaugh
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology*; D003951:Diagnostic Errors; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010296:Parietal Lobe / Q000473:pathology