title: Event time analysis of longitudinal neuroimage data.
abstract: This paper presents a method for the statistical analysis of the associations between longitudinal neuroimaging measurements, e.g., of cortical thickness, and the timing of a clinical event of interest, e.g., disease onset. The proposed approach consists of two steps, the first of which employs a linear mixed effects (LME) model to capture temporal variation in serial imaging data. The second step utilizes the extended Cox regression model to examine the relationship between time-dependent imaging measurements and the timing of the event of interest. We demonstrate the proposed method both for the univariate analysis of image-derived biomarkers, e.g., the volume of a structure of interest, and the exploratory mass-univariate analysis of measurements contained in maps, such as cortical thickness and gray matter density. The mass-univariate method employs a recently developed spatial extension of the LME model. We applied our method to analyze structural measurements computed using FreeSurfer, a widely used brain Magnetic Resonance Image (MRI) analysis software package. We provide a quantitative and objective empirical evaluation of the statistical performance of the proposed method on longitudinal data from subjects suffering from Mild Cognitive Impairment (MCI) at baseline.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: msabuncu@nmr.mgh.harvard.edu.
authors.forename: Mert R
authors.initials: MR
authors.lastname: Sabuncu
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Bernal-Rusiel
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Fischl
mesh_terms: D019985:Benchmarking; D002540:Cerebral Cortex / Q000033:anatomy & histology; D003627:Data Interpretation, Statistical; D006624:Hippocampus / Q000033:anatomy & histology; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D015233:Models, Statistical; D059906:Neuroimaging / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models
keywords: Cox regression; Event time analysis; Linear mixed effects models; Longitudinal studies; Survival analysis
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