Assessing Microstructural Substrates of White Matter Abnormalities: A Comparative Study Using DTI and NODDI.

Inge Timmers,Pew-Thian Yap,Estela Rubio-Gozalbo,Matteo Bastiani,Alard Roebroeck,Bernadette Jansma,Hui Zhang

doi:10.1371/journal.pone.0167884

Abstract

Neurite orientation dispersion and density imaging (NODDI) enables more specific characterization of tissue microstructure by estimating neurite density (NDI) and orientation dispersion (ODI), two key contributors to fractional anisotropy (FA). The present work compared NODDI- with diffusion tensor imaging (DTI)-derived indices for investigating white matter abnormalities in a clinical sample. We assessed the added value of NODDI parameters over FA, by contrasting group differences identified by both models. Diffusion-weighted images with multiple shells were acquired in a group of 8 healthy controls and 8 patients with an inherited metabolic disease. Both standard DTI and NODDI analyses were performed. Tract based spatial statistics (TBSS) was used for group inferences, after which overlap and unique contributions across different parameters were evaluated. Results showed that group differences in NDI and ODI were complementary, and together could explain much of the FA results. Further, compared to FA analysis, NDI and ODI gave a pattern of results that was more regionally specific and were able to capture additional discriminative voxels that FA failed to identify. Finally, ODI from single-shell NODDI analysis, but not NDI, was found to reproduce the group differences from the multi-shell analysis. To conclude, by using a clinically feasible acquisition and analysis protocol, we demonstrated that NODDI is of added value to standard DTI, by revealing specific microstructural substrates to white matter changes detected with FA. As the (simpler) DTI model was more sensitive in identifying group differences, NODDI is recommended to be used complementary to DTI, thereby adding greater specificity regarding microstructural underpinnings of the differences. The finding that ODI abnormalities can be identified reliably using single-shell data may allow the retrospective analysis of standard DTI with NODDI.

Highlights

Diffusion-weighted imaging (DWI) can be used in vivo to assess properties and potential abnormalities of tissue microstructure
The neurite orientation dispersion and density imaging (NODDI) analysis revealed several group differences in neurite density (NDI) and orientation dispersion (ODI) that give a more specific regional pattern of white matter changes as compared to the general pattern of fractional anisotropy (FA) findings (Fig 1): NDI changes were found mainly in bilateral anterior regions, while ODI changes were left lateralized and more posterior
Using a metabolic disease as an example, we demonstrated that the multi-compartment model neurite orientation dispersion and density imaging (NODDI) can be of added value to standard diffusion tensor imaging (DTI) for investigating WM abnormalities

Summary

Introduction

Diffusion-weighted imaging (DWI) can be used in vivo to assess properties and potential abnormalities of tissue microstructure. A variety of parameters can be estimated by measuring the diffusion of water, exploiting the fact that the diffusion is influenced by tissue microstructure. A variety of models are used to model water diffusion. Used–perhaps even the default model- is the single compartment diffusion tensor model [1], with fractional anisotropy (FA) as its most commonly used parameter. This straightforward marker has been studied in the context of brain development and aging [2], and has been found to be reduced in numerous neurological and neurodegenerative diseases [3,4]. It has been suggested that changes in RD reflect de/dysmyelination [8], while AD changes are more related to axonal damage [9], but the interpretation of these markers has been a topic of controversy [10]

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