Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease

Yi Hong; Lauren J O'Donnell; Peter Savadjiev; Fan Zhang; Demian Wassermann; Ofer Pasternak; Hans Johnson; Jane Paulsen; Jean-Paul Vonsattel; Nikos Makris; Carl F Westin; Yogesh Rathi

doi:10.1002/hbm.24217

Back

Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease

Journal article

Open access

Peer reviewed

Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease

Yi Hong, Lauren J O'Donnell, Peter Savadjiev, Fan Zhang, Demian Wassermann, Ofer Pasternak, Hans Johnson, Jane Paulsen, Jean-Paul Vonsattel, Nikos Makris, …

Human brain mapping, Vol.39(10), pp.3871-3883

10/2018

DOI: 10.1002/hbm.24217

PMCID: PMC6160325

PMID: 29797744

Files and links (1)

url

https://doi.org/10.1002/hbm.24217View

Published (Version of record) Open Access

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder that causes progressive breakdown of striatal neurons. Standard white matter integrity measures like fractional anisotropy and mean diffusivity derived from diffusion tensor imaging were analyzed in prodromal-HD subjects; however, they studied either a whole brain or specific subcortical white matter structures with connections to cortical motor areas. In this work, we propose a novel analysis of a longitudinal cohort of 243 prodromal-HD individuals and 88 healthy controls who underwent two or more diffusion MRI scans as part of the PREDICT-HD study. We separately trace specific white matter fiber tracts connecting the striatum (caudate and putamen) with four cortical regions corresponding to the hand, face, trunk, and leg motor areas. A multi-tensor tractography algorithm with an isotropic volume fraction compartment allows estimating diffusion of fast-moving extra-cellular water in regions containing crossing fibers and provides quantification of a microstructural property related to tissue atrophy. The tissue atrophy rate is separately analyzed in eight cortico-striatal pathways as a function of CAG-repeats (genetic load) by statistically regressing out age effect from our cohort. The results demonstrate a statistically significant increase in isotropic volume fraction (atrophy) bilaterally in hand fiber connections to the putamen with increasing CAG-repeats, which connects the genetic abnormality (CAG-repeats) to an imaging-based microstructural marker of tissue integrity in specific white matter pathways in HD. Isotropic volume fraction measures in eight cortico-striatal pathways are also correlated significantly with total motor scores and diagnostic confidence levels, providing evidence of their relevance to HD clinical presentation.

Details

Title: Subtitle: Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease
Creators: Yi Hong - Department of Computer Science; University of Georgia; Athens Georgia
Lauren J O'Donnell - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Peter Savadjiev - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Fan Zhang - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Demian Wassermann - INRIA Sophia Antipolis Mediterranee; Athena team; France
Ofer Pasternak - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Hans Johnson - Department of Psychiatry; University of Iowa; Iowa City Iowa
Jane Paulsen - Department of Psychiatry; University of Iowa; Iowa City Iowa
Jean-Paul Vonsattel - Department of Pathology and Cell Biology; Columbia University; New York New York
Nikos Makris - Department of Psychiatry; Massachusetts General Hospital, Harvard Medical School; Boston Massachusetts
Carl F Westin - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Yogesh Rathi - Department of Radiology, Brigham and Women's Hospital; Harvard Medical School; Boston Massachusetts
Resource Type: Journal article
Publication Details: Human brain mapping, Vol.39(10), pp.3871-3883
DOI: 10.1002/hbm.24217
PMID: 29797744
PMCID: PMC6160325
NLM abbreviation: Hum Brain Mapp
ISSN: 1065-9471
eISSN: 1097-0193
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: P41EB015902, R01MH097979, U01CA199459, U01NS083223, R01NS040068
Language: English
Date published: 10/2018
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: 9984083272802771

Metrics

24 Record Views

10 Times Cited - Web of Science