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Genetic Load Determines Atrophy in Hand Cortico-striatal Pathways in Presymptomatic Huntington's Disease

Institution:
1Department of Computer Science, University of Georgia, Athens, GA, USA.
2Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publisher:
Wiley
Publication Date:
Oct-2018
Journal:
Hum Brain Mapp
Volume Number:
39
Issue Number:
10
Pages:
3871-83
Citation:
Hum Brain Mapp. 2018 Oct;39(10):3871-83.
PubMed ID:
29797744
Keywords:
CAG-repeats, cortico-striatal pathways, diffusion MRI, isotropic volume fraction, prodromal-HD
Appears in Collections:
NAC, LMI, SPL
Sponsors:
R01 NS040068/NS/NINDS NIH HHS/United States
R01 MH097979/MH/NIMH NIH HHS/United States
U01 NS083223/NS/NINDS NIH HHS/United States
U01 CA199459/CA/NCI NIH HHS/United States
P41 EB015902/EB/NIBIB NIH HHS/United States
Generated Citation:
Hong Y., O'Donnell L.J., Savadjiev P., Zhang F., Wassermann D., Pasternak O., Johnson H., Paulsen J., Vonsattel J-P., Makris N., Westin C.F., Rathi Y. Genetic Load Determines Atrophy in Hand Cortico-striatal Pathways in Presymptomatic Huntington's Disease. Hum Brain Mapp. 2018 Oct;39(10):3871-83. PMID: 29797744.
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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.