Application of neurite orientation dispersion and density imaging (NODDI) to a tau pathology model of Alzheimer's disease

Abstract

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.

Characterizing Structural Changes With Evolving Remyelination Following Experimental Demyelination Using High Angular Resolution Diffusion MRI and Texture Analysis

“…NODDI indices derived from the biophysical model may be more sensitive than FA. This is consistent with several other studies showing the greater potential of NODDI parameters than FA, including direct comparison studies in human spinal cord with MS, mouse corpus callosum, and mouse model of human Alzheimer's disease . However, at least one study reported the opposite, the insensitivity of NODDI compared to DTI measures including FA .…”

Ageing and brain white matter structure in 3,513 UK Biobank participants

“…Whereas there is evidence that MD is also more sensitive to age than FA among those with mild stroke48, our sample composition has implications for another aspect of our results. Whereas hippocampal volume and ICVF did not appear to provide unique information about age in this sample, both ICVF (rather than FA)49 and hippocampal volume50 are important dementia biomarkers, emphasizing that our findings, which focus on normal ageing, cannot necessarily be generalized to clinical populations.…”

Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder

“…Neurite orientation-dispersion and density imaging (NODDI) is a recently introduced biophysical diffusion modeling approach that approximates neurites (i.e., axons and dendrites) as a set of sticks with zero radii to capture the extremely restricted diffusion perpendicular to the neurites and unhindered diffusion along them (15). Thus, NODDI is well suited for microstructural modeling of GM tissue, which is primarily composed of dendritic trees and crossing axons, as it permits high dispersion of the neuritic orientations (15,18). This technique characterizes: the spatial configuration of the neurites with the orientation dispersion index (ODI); and tissue microstructural composition with the neuritic density index (NDI), the volume fraction of neurites in brain tissue (15).…”