title: Intracranial volume estimated with commonly used methods could introduce bias in studies including brain volume measurements.
abstract: In brain volumetric studies, intracranial volume (ICV) is often used as an estimate of pre-morbid brain size as well as to compensate for inter-subject variations in head size. However, if the estimated ICV is biased by for example gender or atrophy, it could introduce errors in study results. To evaluate how two commonly used methods for ICV estimation perform, computer assisted reference segmentations were created and evaluated. Segmentations were created for 399 MRI volumes from 75-year-old subjects, with 53 of these subjects having an additional scan and segmentation created at age 80. ICV estimates from Statistical Parametric Mapping (SPM, version 8) and Freesurfer (FS, version 5.1.0) were compared to the reference segmentations, and bias related to skull size (approximated with the segmentation measure), gender or atrophy were tested for. The possible ICV related effect on associations between normalized hippocampal volume and factors gender, education and cognition was evaluated by normalizing hippocampal volume with different ICV measures. Excellent agreement was seen for inter- (r=0.999) and intra- (r=0.999) operator reference segmentations. Both SPM and FS overestimated ICV. SPM showed bias associated with gender and atrophy while FS showed bias dependent on skull size. All methods showed good correlation between time points in the longitudinal data (reference: 0.998, SPM: 0.962, FS: 0.995). Hippocampal volume showed different associations with cognition and gender depending on which ICV measure was used for hippocampal volume normalization. These results show that the choice of method used for ICV estimation can bias results in studies including brain volume measurements.
authors.affiliation: Department of Radiology, Uppsala University, Uppsala, Sweden. Electronic address: richard.nordenskjold@radiol.uu.se.
authors.forename: Richard
authors.initials: R
authors.lastname: Nordenskjöld
authors.forename: Filip
authors.initials: F
authors.lastname: Malmberg
authors.forename: Elna-Marie
authors.initials: EM
authors.lastname: Larsson
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Brooks
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlström
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.forename: Joel
authors.initials: J
authors.lastname: Kullberg
mesh_terms: D000368:Aged; D000465:Algorithms; D016477:Artifacts; D015982:Bias; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods* / Q000706:statistics & numerical data*; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data*; D008297:Male; D009929:Organ Size / Q000502:physiology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013548:Sweden
keywords: Atrophy; Bias; Evaluation; Freesurfer; Intracranial volume; Statistical Parametric Mapping