Journal article
Linking white matter and deep gray matter alterations in premanifest Huntington disease
NeuroImage clinical, Vol.11(C), pp.450-460
2016
DOI: 10.1016/j.nicl.2016.02.014
PMCID: PMC4827723
PMID: 27104139
Abstract
Huntington disease (HD) is a fatal progressive neurodegenerative disorder for which only symptomatic treatment is available. A better understanding of the pathology, and identification of biomarkers will facilitate the development of disease-modifying treatments. HD is potentially a good model of a neurodegenerative disease for development of biomarkers because it is an autosomal-dominant disease with complete penetrance, caused by a single gene mutation, in which the neurodegenerative process can be assessed many years before onset of signs and symptoms of manifest disease. Previous MRI studies have detected abnormalities in gray and white matter starting in premanifest stages. However, the understanding of how these abnormalities are related, both in time and space, is still incomplete. In this study, we combined deep gray matter shape diffeomorphometry and white matter DTI analysis in order to provide a better mapping of pathology in the deep gray matter and subcortical white matter in premanifest HD. We used 296 MRI scans from the PREDICT-HD database. Atrophy in the deep gray matter, thalamus, hippocampus, and nucleus accumbens was analyzed by surface based morphometry, and while white matter abnormalities were analyzed in (i) regions of interest surrounding these structures, using (ii) tractography-based analysis, and using (iii) whole brain atlas-based analysis. We detected atrophy in the deep gray matter, particularly in putamen, from early premanifest stages. The atrophy was greater both in extent and effect size in cases with longer exposure to the effects of the CAG expansion mutation (as assessed by greater CAP-scores), and preceded detectible abnormalities in the white matter. Near the predicted onset of manifest HD, the MD increase was widespread, with highest indices in the deep and posterior white matter. This type of in-vivo macroscopic mapping of HD brain abnormalities can potentially indicate when and where therapeutics could be targeted to delay the onset or slow the disease progression.
Details
- Title: Subtitle
- Linking white matter and deep gray matter alterations in premanifest Huntington disease
- Creators
- Andreia V Faria - The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: afaria1@jhmi.eduJ Tilak Ratnanather - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA; Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USADaniel J Tward - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA; Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USADavid Soobin Lee - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA; Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USAFrieda van den Noort - MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The NetherlandsDan Wu - The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USATimothy Brown - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USAHans Johnson - Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USAJane S Paulsen - Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, IA, USAChristopher A Ross - Division of Neurobiology, Department of Psychiatry, and Departments of Neurology, Neuroscience and Pharmacology, Johns Hopkins University, Baltimore, MD, USALaurent Younes - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA; Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, USA; Department of Applied Mathematics and Statistics, The Johns Hopkins University, Baltimore, MD, USAMichael I Miller - Center for Imaging Science, The Johns Hopkins University, Baltimore, MD, USA; Institute for Computational Medicine, The Johns Hopkins University, Baltimore, MD, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USAPREDICT-HD Investigators and Coordinators of the Huntington Study Group
- Resource Type
- Journal article
- Publication Details
- NeuroImage clinical, Vol.11(C), pp.450-460
- DOI
- 10.1016/j.nicl.2016.02.014
- PMID
- 27104139
- PMCID
- PMC4827723
- NLM abbreviation
- Neuroimage Clin
- ISSN
- 2213-1582
- eISSN
- 2213-1582
- Grant note
- R01 NS040068 / NINDS NIH HHS R01 EB000975 / NIBIB NIH HHS U01 NS082085 / NINDS NIH HHS R03 EB014357 / NIBIB NIH HHS NS40068 / NINDS NIH HHS U01 NS105509 / NINDS NIH HHS R01 NS103475 / NINDS NIH HHS R01-EB000975 / NIBIB NIH HHS U01-NS082085 / NINDS NIH HHS P50NS16375 / NINDS NIH HHS P41-EB015909 / NIBIB NIH HHS P41 EB015909 / NIBIB NIH HHS R01-EB008171 / NIBIB NIH HHS R01 NS084957 / NINDS NIH HHS P01 NS016375 / NINDS NIH HHS R01 EB008171 / NIBIB NIH HHS R03-EB014357 / NIBIB NIH HHS
- Language
- English
- Date published
- 2016
- 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
- 9984221730402771
Metrics
18 Record Views