title: Intracranial volume normalization methods: considerations when investigating gender differences in regional brain volume.
abstract: Intracranial volume (ICV) normalization of regional brain volumes (v) is common practice in volumetric studies of the aging brain. Multiple normalization methods exist and this study aimed to investigate when each method is appropriate to use in gender dimorphism studies and how differences in v are affected by the choice of method. A new method based on weighted ICV matching is also presented. Theoretical reasoning and simulated experiments were followed by an evaluation using real data comprising 400 subjects, all 75 years old, whose ICV was segmented with a gold standard method. The presented method allows good visualization of volume relation between gender groups. A different gender dimorphism in volume was found depending on the normalization method used for both simulated and real data. Method performance was also seen to depend on the slope (B) and intercept (m) from the linear relation between v and ICV (v=B·ICV+m) as well as gender distribution in the cohort. A suggested work-flow for selecting ICV normalization method when investigating gender related differences in regional brain volume is presented.
authors: Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Electronic address: richard.nordenskjold@radiol.uu.se.
authors: Richard
authors: R
authors: Nordenskjöld
authors: Centre for Image Analysis, Uppsala University, Uppsala, Sweden.
authors: Filip
authors: F
authors: Malmberg
authors: Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
authors: Elna-Marie
authors: EM
authors: Larsson
authors: King׳s College London, Institute of Psychiatry, London, UK; NIHR Biomedical Research Centre for Mental Health and NIHR Biomedical Research Unit for Dementia, London, UK.
authors: Andrew
authors: A
authors: Simmons
authors: Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
authors: Håkan
authors: H
authors: Ahlström
authors: Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden; AstraZeneca, Mölndal, Sweden.
authors: Lars
authors: L
authors: Johansson
authors: Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
authors: Joel
authors: J
authors: Kullberg
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000033:anatomy & histology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009929:Organ Size; D012727:Sex Characteristics
keywords: Dimorphism; Human brain; Intracranial volume; Normalization; Sex difference; Volume