Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models

Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) mo...

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Published inNeuroImage (Orlando, Fla.) Vol. 66; pp. 249 - 260
Main Authors Bernal-Rusiel, Jorge L., Greve, Douglas N., Reuter, Martin, Fischl, Bruce, Sabuncu, Mert R.
Format Journal Article
LanguageEnglish
Published Amsterdam Elsevier Inc 01.02.2013
Elsevier
Elsevier Limited
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Abstract Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer — a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences. ► We discuss Linear Mixed Effects (LME) models in the context of longitudinal imaging. ► We contrast LME with widely used methods in longitudinal imaging. ► We illustrate, validate and benchmark LME-based computational tools. ► These tools will be freely available in FreeSurfer.
AbstractList Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer - a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences.Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer - a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences.
Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer a a popular Magnetic Resonance Image (MRI) analysis software package.
Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer – a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer’s patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences.
Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer -- a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitativeempiricalevaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences.
Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer — a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences. ► We discuss Linear Mixed Effects (LME) models in the context of longitudinal imaging. ► We contrast LME with widely used methods in longitudinal imaging. ► We illustrate, validate and benchmark LME-based computational tools. ► These tools will be freely available in FreeSurfer.
Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the analysis of LNI data and widely used methods are sub-optimal for the types of data encountered in real-life studies. Linear Mixed Effects (LME) modeling, a mature approach well known in the statistics community, offers a powerful and versatile framework for analyzing real-life LNI data. This article presents the theory behind LME models, contrasts it with other popular approaches in the context of LNI, and is accompanied with an array of computational tools that will be made freely available through FreeSurfer - a popular Magnetic Resonance Image (MRI) analysis software package. Our core contribution is to provide a quantitative empirical evaluation of the performance of LME and competing alternatives popularly used in prior longitudinal structural MRI studies, namely repeated measures ANOVA and the analysis of annualized longitudinal change measures (e.g. atrophy rate). In our experiments, we analyzed MRI-derived longitudinal hippocampal volume and entorhinal cortex thickness measurements from a public dataset consisting of Alzheimer's patients, subjects with mild cognitive impairment and healthy controls. Our results suggest that the LME approach offers superior statistical power in detecting longitudinal group differences.
Author Fischl, Bruce
Greve, Douglas N.
Reuter, Martin
Bernal-Rusiel, Jorge L.
Sabuncu, Mert R.
AuthorAffiliation 1 Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA
2 Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA
3 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA
AuthorAffiliation_xml – name: 2 Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA
– name: 3 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA
– name: 1 Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA
Author_xml – sequence: 1
  givenname: Jorge L.
  surname: Bernal-Rusiel
  fullname: Bernal-Rusiel, Jorge L.
  organization: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA
– sequence: 2
  givenname: Douglas N.
  surname: Greve
  fullname: Greve, Douglas N.
  organization: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA
– sequence: 3
  givenname: Martin
  surname: Reuter
  fullname: Reuter, Martin
  organization: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA
– sequence: 4
  givenname: Bruce
  surname: Fischl
  fullname: Fischl, Bruce
  organization: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA
– sequence: 5
  givenname: Mert R.
  surname: Sabuncu
  fullname: Sabuncu, Mert R.
  email: msabuncu@nmr.mgh.harvard.edu
  organization: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School/Massachusetts General Hospital, Charlestown, MA, USA
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Keywords Linear Mixed Effects models
Longitudinal studies
Statistical analysis
Models
Language English
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Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators is available at http://tinyurl.com/ADNI-main.
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Snippet Longitudinal neuroimaging (LNI) studies are rapidly becoming more prevalent and growing in size. Today, no standardized computational tools exist for the...
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SubjectTerms Aged
Aged, 80 and over
Algorithms
Alzheimer Disease - pathology
Biological and medical sciences
Brain - pathology
Cognitive Dysfunction - pathology
Female
Fundamental and applied biological sciences. Psychology
Humans
Hypothesis testing
Image Processing, Computer-Assisted - methods
Linear Mixed Effects models
Linear Models
Longitudinal Studies
Magnetic Resonance Imaging
Male
Medical imaging
Middle Aged
Parameter estimation
Software
Standard deviation
Statistical analysis
Statistical methods
Studies
Variance analysis
Vertebrates: nervous system and sense organs
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Title Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models
URI https://www.clinicalkey.com/#!/content/1-s2.0-S1053811912010683
https://dx.doi.org/10.1016/j.neuroimage.2012.10.065
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Volume 66
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