Journal
NEUROIMAGE
Volume 125, Issue -, Pages 739-744Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2015.10.043
Keywords
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Funding
- Medical Research Council [MR/J013110/1]
- King's College London and UCL Comprehensive Cancer Imaging Centre CR-UK EPSRC [000012287]
- MRC [MR/J013110/1]
- Eli Lily and Company
- UK Regenerative Medicine Platform Safety Hub (MRC) [MR/K026739/1, IRIS 104393]
- EPSRC [EP/L022680/1]
- NC3Rs studentship [NC/K500276/1]
- UK Medical Research Council Doctoral Training Grant Studentship [MR/J500422/1, MR/G0900207-3/1]
- Engineering and Physical Sciences Research Council [EP/M020533/1, EP/M029778/1, EP/L022680/1, EP/N018702/1, EP/G007748/1, EP/M00855X/1] Funding Source: researchfish
- Medical Research Council [MR/K026739/1, MR/J013110/1, G0601056, MR/M009106/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K500276/1] Funding Source: researchfish
- EPSRC [EP/L022680/1, EP/M020533/1, EP/N018702/1, EP/M00855X/1, EP/G007748/1, EP/M029778/1] Funding Source: UKRI
- MRC [MR/K026739/1, MR/J013110/1, MR/M009106/1, G0601056] Funding Source: UKRI
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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 8.5 months 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. (C) 2015 Elsevier Inc. All rights reserved.
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