Discriminating subcortical ischemic vascular disease and Alzheimer's disease by diffusion kurtosis imaging in segregated thalamic regions

Abstract

Differentiating between subcortical ischemic vascular disease (SIVD), Alzheimer's disease (AD), and normal cognition (NC) remains a challenge, and reliable neuroimaging biomarkers are needed. The current study, therefore, investigated the discriminative ability of diffusion kurtosis imaging (DKI) metrics in segregated thalamic regions and compare with diffusion tensor imaging (DTI) metrics. Twenty-three SIVD patients, 30 AD patients, and 24 NC participants underwent brain magnetic resonance imaging. The DKI metrics including mean kurtosis (MK), axial kurtosis (K_axial ) and radial kurtosis (K_radial ) and the DTI metrics including diffusivity and fractional anisotropy (FA) were measured within the whole thalamus and segregated thalamic subregions. Strategic correlations by group, thalamo-frontal connectivity, and canonical discriminant analysis (CDA) were used to demonstrate the discriminative ability of DKI for SIVD, AD, and NC. Whole and segregated thalamus analysis suggested that DKI metrics are less affected by white matter hyperintensities compared to DTI metrics. Segregated thalamic analysis showed that MK and K_radial were notably different between SIVD and AD/NC. The correlation analysis between K_axial and MK showed a nonsignificant relationship in SIVD group, a trend of negative relationship in AD group, and a significant positive relationship in NC group. A wider spatial distribution of thalamo-frontal connectivity differences across groups was shown by MK compared to FA. CDA showed a discriminant power of 97.4% correct classification using all DKI metrics. Our findings support that DKI metrics could be more sensitive than DTI metrics to reflect microstructural changes within the gray matter, hence providing complementary information for currently outlined pathogenesis of SIVD and AD.

Keywords: Alzheimer's disease; canonical discriminant analysis; dementia; diffusion kurtosis imaging; diffusion tensor imaging; subcortical ischemic vascular disease; thalamus.

FIGURE 1

(a) Segregated thalamic subregions used in this study. (b) The final ventricle‐masked segregated thalamus atlas was overlaid onto the averaged b0 images across all three groups (SIVD, subcortical ischemic vascular disease; AD, Alzheimer's disease; NC, normal cognition)

FIGURE 2

Correlation analysis between (a–c) FA and MD as well as (d–f) MK and MD across all three groups (SIVD, subcortical ischemic vascular disease; AD, Alzheimer's disease; NC, normal cognition; MD, mean diffusivity; FA, fractional anisotropy; MK, mean kurtosis)

FIGURE 3

Correlation analysis among DTI and DKI metrics across the three groups. (a–c) Correlations between MD and D _axial/D _radial, and (d–f) Correlations between MK and K _axial/K _radial. DTI, diffusion tensor imaging; DKI, diffusion kurtosis imaging; SIVD, subcortical ischemic vascular disease; AD, Alzheimer's disease; NC, normal cognition; D _axial, axial diffusivity; D _radial, radial diffusivity; MD, mean diffusivity; FA, fractional anisotropy; K _axial, axial kurtosis; K _radial, radial kurtosis; MK, mean kurtosis

FIGURE 4

Between‐group comparisons of (a) FA, (b) MK, (c) K _axial, and (d) K _radial in segregated thalamic regions. Thin brackets indicate between‐group differences with significant p values <.05 after controlling for age and education (FDR uncorrected). Asterisks (*) indicate between‐group differences with significant p values <.05 after controlling for age and education (FDR corrected). Daggers (^†) indicate significant between‐group differences with significant p values <.05 noted after controlling for age, education, and the Fazekas scale. SIVD, subcortical ischemic vascular disease; AD, Alzheimer's disease; NC, normal cognition; DKI, diffusion kurtosis imaging; FA, fractional anisotropy; MK, mean kurtosis; K _axial, axial kurtosis; K _radial, radial kurtosis; PUL, pulvinar; ANT, anterior; MedioD, mediodorsal; VLD, ventral–lateral–dorsal; C, central; VA, ventral‐anterior; VLV, ventral–lateral–ventral; L, left; R = right

FIGURE 5

Diffusivity metrics, (a) D _axial, (b) D _radial, and (c) MD, in segregated thalamic regions among normal cognition (NC, n = 24), Alzheimer's disease (AD, n = 30), and subcortical ischemic vascular disease (SIVD, n = 23) groups. Thin brackets indicate between‐group differences with significant p values <.05 after controlling for age and education (FDR uncorrected). Asterisks (*) indicate between‐group differences with significant p values <.05 after controlling for age and education (FDR corrected). No significant between‐group differences with significant p values <.05 is noted after controlling for age, education, and the Fazekas scale. MD, mean diffusivity; D _axial, axial diffusivity; D _radial, radial diffusivity; PUL, pulvinar; ANT, anterior; MedioD, mediodorsal; VLD, ventral–lateral–dorsal; C, central; VA, ventral‐anterior; VLV, ventral–lateral–ventral; L, left; R, right

FIGURE 6

Between‐group comparisons of thalamo‐frontal connectivity. (a) FA connectivity and (b) MK connectivity. Asterisks (*) indicate between‐group differences with significant p values <.05 after controlling for age and education (FDR corrected). No significant between‐group differences with significant p values <.05 are noted after controlling for age, education, and the Fazekas scale. ANT, anterior; MedioD, mediodorsal; VA, ventral‐anterior; SFG, the superior frontal gyrus; R, right; L, left; FA, fractional anisotropy; MK, mean kurtosis

FIGURE 7

Canonical discriminant analysis using DKI metrics. SIVD, subcortical ischemic vascular disease; AD, Alzheimer's disease; NC, normal cognition