Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease.
Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK; Department of Medical Physics and Bioengineering, Saolta University Health Care Group, University Hospital Galway, Newcastle Road, Galway, H91 YR71, Ireland. Electronic address: n.colgan@ucl.ac.uk.
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Colgan
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK; Department of Computer Science & Centre for Medical Image Computing, University College London, UK.
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B
Siow
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
J M
JM
O'Callaghan
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
I F
IF
Harrison
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
J A
JA
Wells
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
H E
HE
Holmes
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
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O
Ismail
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK; Department of Computer Science & Centre for Medical Image Computing, University College London, UK.
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Richardson
Department of Computer Science & Centre for Medical Image Computing, University College London, UK.
D C
DC
Alexander
Eli Lilly & Co. Ltd, Lilly Corporate Center, Indianapolis, IN 46285, USA.
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Collins
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square London, UK.
E M
EM
Fisher
Eli Lilly & Co. Ltd, Lilly Corporate Center, Indianapolis, IN 46285, USA.
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Johnson
Eli Lilly & Co. Ltd, Lilly Corporate Center, Indianapolis, IN 46285, USA.
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AJ
Schwarz
Eli Lilly & Co. Ltd, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
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Z
Ahmed
Eli Lilly & Co. Ltd, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
M J
MJ
O'Neill
Eli Lilly & Co. Ltd, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
T K
TK
Murray
Department of Computer Science & Centre for Medical Image Computing, University College London, UK.
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H
Zhang
UCL Centre for Advanced Biomedical Imaging , Division of Medicine, University College London, UK.
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Lythgoe
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping / Q000379:methods*; D056324:Diffusion Tensor Imaging / Q000379:methods; D004195:Disease Models, Animal; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
D016875:tau Proteins