1. Genetic load determines atrophy in hand cortico-striatal pathways in presymptomatic Huntington's disease
- Author
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Fan Zhang, Demian Wassermann, Ofer Pasternak, Nikolaos Makris, Peter Savadjiev, Hans J. Johnson, Yi Hong, Lauren J. O'Donnell, Carl-Fredrik Westin, Jean-Paul Vonsattel, Yogesh Rathi, Jane S. Paulsen, Department of Computer Science [Athens GA], University of Georgia [USA], Departments of Psychiatry and Radiology [Boston], Brigham and Women's Hospital [Boston], Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Computational Imaging of the Central Nervous System (ATHENA), Inria Sophia Antipolis - Méditerranée (CRISAM), University of Iowa [Iowa City], Columbia University [New York], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Laboratory of Mathematics in Imaging [Boston], Harvard Medical School [Boston] (HMS), Department of Computer Science, University of Georgia, Modelling brain structure, function and variability based on high-field MRI data ( PARIETAL ), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Computational Imaging of the Central Nervous System ( ATHENA ), Inria Sophia Antipolis - Méditerranée ( CRISAM ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), University of Iowa [Iowa], Harvard Medical School [Boston] ( HMS ), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
- Subjects
Male ,Striatum ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Trinucleotide Repeats ,CAG-repeats ,Neural Pathways ,Isotropic volume fraction ,Longitudinal Studies ,Aged, 80 and over ,Cortico-striatal pathways ,Radiological and Ultrasound Technology ,Putamen ,Motor Cortex ,Middle Aged ,White Matter ,Diffusion Tensor Imaging ,Huntington Disease ,medicine.anatomical_structure ,Neurology ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Genetic Load ,Anatomy ,Tractography ,Adult ,Adolescent ,[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,Prodromal Symptoms ,Biology ,Article ,Diffusion MRI ,White matter ,Young Adult ,03 medical and health sciences ,Atrophy ,Huntington's disease ,[ PHYS.PHYS.PHYS-BIO-PH ] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,Fractional anisotropy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Equal contribution Keywords: Prodromal-HD ,Aged ,medicine.disease ,Prodromal-HD ,[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,Caudate Nucleus ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; 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 Hong et al., Genetic load determines hand atrophy in preHD 2 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.
- Published
- 2018