Abstract

Tractography based on Diffusion Tensor Imaging (DTI) represents a valuable tool for investigating brain white matter (WM) microstructure, allowing the computation of damage-related diffusion parameters such as Fractional Anisotropy (FA) in specific WM tracts. This technique appears relevant in the study of pathologies in which brain disconnection plays a major role, such as, for instance, Alzheimer's Disease (AD). Previous DTI studies have reported inconsistent results in defining WM abnormalities in AD and in its prodromal stage (i.e., amnestic Mild Cognitive Impairment; aMCI), especially when investigating the corpus callosum (CC). A reason for these inconsistencies is the use of different processing techniques, which may strongly influence the results. The aim of the current study was to compare a novel atlas-based tractography approach, that sub-divides the CC in eight portions, with Tract-Based Spatial Statistics (TBSS) when used to detect specific patterns of CC FA in AD at different clinical stages. FA data were obtained from 76 subjects (37 with mild AD, 19 with aMCI and 20 elderly healthy controls, HC) and analyzed using both methods. Consistent results were obtained for the two methods, concerning the comparisons AD vs. HC (significantly reduced FA in the whole CC of AD patients) and AD vs. aMCI (significantly reduced FA in the frontal portions of the CC in AD patients), thus identifying a relative preservation of the frontal CC regions in aMCI patients compared to AD. Conversely, the atlas-based method but not the TBSS showed the ability to detect a selective FA change in the CC parietal, left temporal and occipital regions of aMCI patients compared to HC. This finding indicates that an analysis including a higher number of voxels (with no restriction to tract skeletons) may detect characteristic pattern of FA in the CC of patients with preclinical AD, when brain atrophy is still modest.

Highlights

  • Tractography based on Diffusion Tensor Imaging (DTI) represents a powerful tool, allowing the investigation of white matter (WM) integrity in the human brain in vivo, through the reconstruction of 3D bundle trajectories

  • The results reported by the atlas-based analysis agreed with those of the Tract-Based Spatial Statistics (TBSS) regarding the comparisons of Alzheimer’s Disease (AD) vs. healthy controls (HC) and AD vs. amnestic Mild Cognitive Impairment (aMCI)

  • Significantly reduced Fractional Anisotropy (FA) values were found in all corpus callosum (CC) portions of AD patients compared to HC, and in the frontal CC regions (CC1-CC2-CC3) of AD compared to aMCI patients

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Summary

Introduction

Tractography based on Diffusion Tensor Imaging (DTI) represents a powerful tool, allowing the investigation of white matter (WM) integrity in the human brain in vivo, through the reconstruction of 3D bundle trajectories. Several previous studies have used DTI and tractography to assess WM damage in patients with Alzheimer’s Disease (AD) and amnestic Mild Cognitive Impairment (aMCI), a clinical condition widely considered as a prodromal stage of AD [1]. DTI appears useful in this case for the assessment of WM integrity, investigated through the observation of water molecule diffusion anisotropy [4]. This characteristic is commonly evaluated by means of the computation of Fractional Anisotropy (FA), an index derived from the tensor eigenvalues, that quantifies the diffusion directionality of water molecules [5].

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