title: Neurobiological origin of spurious brain morphological changes: A quantitative MRI study.
abstract: The high gray-white matter contrast and spatial resolution provided by T1-weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1-weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1-weighted images (R1 (=1/T1), R2 *, and PD) in a large cohort of healthy subjects (n = 120, aged 18-87 years). Synthetic T1-weighted images were calculated from these quantitative maps and used to extract morphometry features-gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue-myelination, iron, and water content-on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801-1815, 2016. © 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Lorio
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Ferath
authors.initials: F
authors.lastname: Kherif
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Ruef
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Lester
authors.initials: L
authors.lastname: Melie-Garcia
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Frackowiak
authors.affiliation: Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, UCL, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Ashburner
authors.affiliation: Department of Clinical Sciences, Lund University, Medical Radiation Physics, Lund, Sweden.
authors.forename: Gunther
authors.initials: G
authors.lastname: Helms
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lutti
authors.affiliation: LREN - Department of Clinical Neurosciences, CHUV, University of Lausanne, Lausanne Switzerland.|Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Bodgan
authors.initials: B
authors.lastname: Draganski
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: MPRAGE; T1 mapping; T1-weighted images; cortical thickness; gray-matter volume; in vivo histology; quantitative MRI; voxel-based morphometry