Distinctive disruption patterns of white matter tracts in Alzheimer's disease with full diffusion tensor characterization

Abstract

To characterize the white matter structural changes at the tract level and tract group level, comprehensive analysis with 4 metrics derived from diffusion tensor imaging (DTI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD), was conducted. Tract groups, namely limbic, commissural, association, and projection tracts, include white matter tracts of similar functions. Diffusion tensor imaging data were acquired from 61 subjects (26 Alzheimer's disease [AD], 11 subjects with amnestic mild cognitive impairment [aMCI], and 24 age-matched controls). An atlas-based approach was used to survey 30 major cerebral white matter tracts with the measurements of FA, MD, AxD, and RD. Regional cortical atrophy and cognitive functions of AD patients were also measured to correlate with the structural changes of white matter. Synchronized structural changes of cingulum bundle and fornix, both of which are part of limbic tract group, were revealed. Widespread yet distinctive structural changes were found in limbic, commissural, association, and projection tract groups between control and AD subjects. Specifically, FA, MD, and RD of limbic tracts, FA, MD, AxD, and RD of commissural tracts, MD, AxD, and RD of association tracts, and MD and AxD of projection tracts are significantly different between AD patients and control subjects. In contrast, the comparison between aMCI and control subjects shows disruption only in the limbic and commissural tract groups of aMCI subjects. MD values of all tract groups of AD patients are significantly correlated to cognitive functions. Difference between AD and control and that between aMCI and control indicates a progression pattern of white matter disruption from limbic and commissural tract group to other tract groups. High correlation between FA, MD, and RD measurements from limbic tracts and cortical atrophy suggests the disruption of the limbic tract group is caused by the neuronal damage.

Figure 1

Projection of FA value to the core white matter. Green skeleton is overlaid on the averaged FA map; (b) the ICBM-DTI-81 digital white matter atlas; (c) as an example, the genu of corpus callosum (GCC) (yellow shadow) is transferred from the digital atlas to cover the green skeleton overlaid on the averaged FA map. Abbreviations of the white matter tract names can be found in the legend of Fig. 2.

Figure 2

Mean FA (gray scale) and skeleton of all subjects overlaid by the atlas labels in the ICBM-DTI-81 space. Colored regions indicate major white matter tracts. The skeleton from averaged FA maps is shown as white solid curve. L and R indicate left and right. Abbreviations of white matter tracts are as follows. ACR: Anterior corona radiata; ALIC: Anterior limb of internal capsule; BCC: Body of corpus callosum; CGC: Cingulum bundle at cingulate gyrus; CGH: Cingulum bundle in hippocampus; CST: Corticospinal tract; EC: External capsule; FX: Fornix; FX-B: Body of fornix; GCC: Genu of corpus callosum; IFO: Inferior fronto-occipital fasciculus left; ILF: Inferior longitudinal fasciculus; PCR: Posterior corona radiate; PLIC: Posterior limb of internal capsule; PTR: Posterior thalamic radiation; RLIC: Retrolenticular part of internal capsule; SCC: Splenium of corpus callosum; SCR: Superior corona radiate; SLF: Superior longitudinal fasciculus; ST: Stria terminalis; UNC: Uncinate fasciculus.

Figure 3

Synchronized changes of FA, MD and RD from left to right of fornix (FX, blue) and cingulum bundle (CG, red), both of which are part of limbic tract group. Each point represents data from an AD patient. The horizontal axis indicates index of different AD patients. Correlation coefficient (R) and p value of correlation are also displayed in each panel.

Figure 4

Boxplots of FA, MD, AxD and RD of limbic, commissural, association and projection tract groups for AD patients (left of the box pair) compared with the controls (right of the box pair). Statistically significant differences after FDR correction are marked with asterisks.

Figure 5

Tensor change profiles of limbic, commissural, association and projection tract groups reflected by full tensor characterization of FA, MD, AxD and RD, the four metrics derived from diffusion tensor.

Figure 6

Statistically significant correlations (after age and education correction) between MD and CERAD total scores of AD patients for all limbic, commissural, association and projection tract groups.

Figure 7

Cortical atrophy t value map (a) is displayed in the top panel. Correlation coefficient maps for correlation of FA (b), MD (c), AxD (d) and RD (e) of limbic tract group with cortical atrophy are displayed in the lower panels. The top and bottom color bars indicate t value of cortical atrophy and correlation coefficient, respectively.