Ex vivo 100 μm isotropic diffusion MRI-based tractography of connectivity changes in the end-stage R6/2 mouse model of Huntington's disease  

作　　者：Ashwinee Manivannan Lesley M.Foley T.Kevin Hitchens Ivan Rattray Gillian P.Bates Michel Modo 

机构地区：[1]Department of Neuroscience,University of Pittsburgh,Pittsburgh,Pennsylvania,USA [2]Animal Imaging Center,University of Pittsburgh,Pittsburgh,Pennsylvania,USA [3]Department of Neurobiology,University of Pittsburgh,Pittsburgh,Pennsylvania,USA [4]Department of Neurodegenerative Disease,Queen Square Institute of Neurology,Huntington's Disease Centre and UK Dementia Research Institute at UCL,University College London,London,UK [5]Department of Radiology,University of Pittsburgh,Pittsburgh,Pennsylvania,USA [6]Department of Bioengineering,University of Pittsburgh,Pittsburgh,Pennsylvania,USA [7]Center for the Neural Basis of Cognition,University of Pittsburgh,Pittsburgh,Pennsylvania,USA

出　　处：《Neuroprotection》2023年第1期66-83,共18页神经保护（英文）

基　　金：Supported by NINDS(R21NS118399).

摘　　要：Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructural changes within brain tissue are expected to precede this volumetric decline.The tissue microstructure can be assayed non-invasively using diffusion MRI,which also allows a tractographic analysis of brain connectivity.Methods:We here used ex vivo diffusion MRI(11.7 T)to measure microstructural changes in different brain regions of end-stage(14 weeks of age)wild type and R6/2 mice(male and female)modeling Huntington's disease.To probe the microstructure of different brain regions,reduce partial volume effects and measure connectivity between different regions,a 100μm isotropic voxel resolution was acquired.Results:Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice,mean,axial,and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice.Whole brain streamlines were only reduced in male R6/2 mice,but streamline density was increased.Region-to-region tractography indicated reductions in connectivity between the cortex,hippocampus,and thalamus with the striatum,as well as within the basal ganglia(striatum—globus pallidus—subthalamic nucleus—substantia nigra—thalamus).Conclusions:Biological sex and left/right hemisphere affected tractographic results,potentially reflecting different stages of disease progression.This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions.In a translation setting,these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models,as well as patients with Huntington's disease.

关 键 词：CONNECTOME diffusion tensor imaging Huntington's disease MOUSE MRI TRACTOGRAPHY 

分 类 号：R741[医药卫生—神经病学与精神病学]