Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease

Dan Wu; Andreia V Faria; Laurent Younes; Susumu Mori; Timothy Brown; Hans Johnson; Jane S Paulsen; Christopher A Ross; Michael I Miller; PREDICT-HD Investigators and Coordinators of the Huntington Study Group

doi:10.1002/hbm.23713

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Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease

Journal article

Open access

Peer reviewed

Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease

Dan Wu, Andreia V Faria, Laurent Younes, Susumu Mori, Timothy Brown, Hans Johnson, Jane S Paulsen, Christopher A Ross, Michael I Miller and PREDICT-HD Investigators and Coordinators of the Huntington Study Group

Human brain mapping, Vol.38(10), pp.5035-5050

10/2017

DOI: 10.1002/hbm.23713

PMCID: PMC5766002

PMID: 28657159

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Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that progressively affects motor, cognitive, and emotional functions. Structural MRI studies have demonstrated brain atrophy beginning many years prior to clinical onset ("premanifest" period), but the order and pattern of brain structural changes have not been fully characterized. In this study, we investigated brain regional volumes and diffusion tensor imaging (DTI) measurements in premanifest HD, and we aim to determine (1) the extent of MRI changes in a large number of structures across the brain by atlas-based analysis, and (2) the initiation points of structural MRI changes in these brain regions. We adopted a novel multivariate linear regression model to detect the inflection points at which the MRI changes begin (namely, "change-points"), with respect to the CAG-age product (CAP, an indicator of extent of exposure to the effects of CAG repeat expansion). We used approximately 300 T1-weighted and DTI data from premanifest HD and control subjects in the PREDICT-HD study, with atlas-based whole brain segmentation and change-point analysis. The results indicated a distinct topology of structural MRI changes: the change-points of the volumetric measurements suggested a central-to-peripheral pattern of atrophy from the striatum to the deep white matter; and the change points of DTI measurements indicated the earliest changes in mean diffusivity in the deep white matter and posterior white matter. While interpretation needs to be cautious given the cross-sectional nature of the data, these findings suggest a spatial and temporal pattern of spread of structural changes within the HD brain. Hum Brain Mapp 38:5035-5050, 2017. © 2017 Wiley Periodicals, Inc.

Adult

Atlases as Topic

Atrophy

Brain - diagnostic imaging

Brain - pathology

Brain - physiopathology

Cohort Studies

Cross-Sectional Studies

Diffusion Tensor Imaging - methods

Disease Progression

Female

Humans

Huntington Disease - diagnostic imaging

Huntington Disease - genetics

Huntington Disease - pathology

Huntington Disease - physiopathology

Linear Models

Magnetic Resonance Imaging - methods

Male

Middle Aged

Multivariate Analysis

Organ Size

Prodromal Symptoms

Trinucleotide Repeat Expansion

Details

Title: Subtitle: Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease
Creators: Dan Wu - The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
Andreia V Faria - The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
Laurent Younes - Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland
Susumu Mori - F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland
Timothy Brown - Center for Imaging Science, Johns Hopkins University, Baltimore, Maryland
Hans Johnson - Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa
Jane S Paulsen - Departments of Psychiatry, Neurology, Psychology and Neurosciences, University of Iowa, Iowa City, Iowa
Christopher A Ross - Division of Neurobiology, Departments of Psychiatry, Neurology, Neuroscience and Pharmacology, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Michael I Miller - Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland
PREDICT-HD Investigators and Coordinators of the Huntington Study Group
Resource Type: Journal article
Publication Details: Human brain mapping, Vol.38(10), pp.5035-5050
DOI: 10.1002/hbm.23713
PMID: 28657159
PMCID: PMC5766002
NLM abbreviation: Hum Brain Mapp
ISSN: 1065-9471
eISSN: 1097-0193
Grant note: R01 NS040068 / NINDS NIH HHS P41 EB015909 / NIBIB NIH HHS R01 EB000975 / NIBIB NIH HHS U01 NS082085 / NINDS NIH HHS R01 NS084957 / NINDS NIH HHS R01 NS086888 / NINDS NIH HHS P50 NS016375 / NINDS NIH HHS R01 EB008171 / NIBIB NIH HHS R21 NS098018 / NINDS NIH HHS
Language: English
Date published: 10/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Psychiatry; Psychological and Brain Sciences; The Iowa Institute for Biomedical Imaging; The Iowa Initiative for Artificial Intelligence; Iowa Informatics Initiative
Record Identifier: 9984221629802771

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