1Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 2Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
The aim of the study is to investigate the diffusion characteristics of Alzheimer’s disease (AD) patients using an ultra-high b-values apparent diffusion coefficient (ADC_uh) and diffusion kurtosis imaging (DKI). A total of 31 AD patients and 20 healthy controls (HC) who underwent both MRI examination and clinical assessment were included in this study. Diffusion weighted imaging (DWI) was acquired with 14 b-values in the range of 0 and 5000 s/mm2. Diffusivity was analyzed in selected regions, including the amygdala (AMY), hippocampus (HIP), thalamus (THA), caudate (CAU), globus pallidus (GPA), lateral ventricles (LVe), white matter (WM) of the frontal lobe (FL), WM of the temporal lobe (TL), WM of the parietal lobe (PL) and centrum semiovale (CS). The mean, median, skewness and kurtosis of the conventional apparent diffusion coefficient (ADC), DKI (including two variables, Dapp and Kapp) and ADC_uh values were calculated for these selected regions. Compared to the HC group, the ADC values of AD group were significantly higher in the right HIP and right PL (WM), while the ADC_uh values of the AD group increased significantly in the WM of the bilateral TL and right CS. In the AD group, the Kapp values in the bilateral LVe, bilateral PL/left TL (WM) and right CS were lower than those in the HC group, while the Dapp value of the right PL (WM) increased. The ADC_uh value of the right TL was negatively correlated with MMSE (mean, r=-0.420, p=0.019). The ADC value and Dapp value have the same regions correlated with MMSE. Compared with the ADC_uh, combining ADC_uh and ADC parameters will result in a higher AUC (0.894, 95%CI=0.803-0.984, p=0.022). Comparing to ADC or DKI, ADC_uh has no significant difference in the detectability of AD, but ADC_uh can better reflect characteristic alternation in unconventional brain regions of AD patients.
Figure 1. Selections of region of interest. (A, C) The selected ROIs on the vcDWI maps. (B, D) The ROIs were projected onto the ADC_uh maps. The yellow part is the ROI range. AMY, amygdala; HIP, hippocampus; THA, thalamus; CAU, caudate; GPA, globus pallidus; LVe, lateral ventricles; FL, frontal lobe (WM); TL, temporal lobe (WM); PL, parietal lobe (WM); CS, centrum semiovale.
Table 1 Demographic and cognitive characteristics of all participants.
Figure 2. Receiver-operating characteristic curves (ROC) of classifications between AD and HC patients. ADC, ADC_uh, and DKI were separately assessed for differential diagnosis. Then, any combination of them was assessed separately. Finally, all of them was assessed together. Compared to ADC_uh, a higher AUC was obtained by combining ADC_uh values and ADC values (0.897, 95% CI=0.779-0.964, p=0.022). There was no significant difference between the other ROCs. The diagonal line represents a random classification performance.
Mean ± SD
right HIP mean (×10-3mm/s)
right HIP median (×10-3mm/s)
left CAU skewness
right LVe skewness
left FL kurtosis
right PL mean (×10-3mm/s)
right PL median (×10-3mm/s)
left THA mean (×10-3mm/s)
left LVe kurtosis
right TL mean (×10-3mm/s)
right TL median (×10-3mm/s)
left TL mean (×10-3mm/s)
left TL median (×10-3mm/s)
right CS mean (×10-3mm/s)
right CS median (×10-3mm/s)
Table 2 Comparisons of regional diffusion intensity in ADC or ADC_uh between AD and HC group.
left FL kurtosis
right PL mean (×10-3mm/s)
right PL median (×10-3mm/s)
right THA median
right LVe mean
left LVe mean
left LVe median
right FL kurtosis
left FL kurtosis
left TL mean
left TL median
right PL mean
right PL median
left PL mean
left PL median
right CS mean
right CS median
Table 3 Comparisons of regional diffusion intensities in Dapp or Kapp between the AD and HC groups.
Figure 3. Bland-Altman plots of reproducibility of MRI. Bland-Altman plots for ADC mean (A), ADC_uh mean (B), Dapp mean (C) and Kapp mean (D) show a low mean difference between the two tests (continuous line: mean difference, dashed lines: 95% confidence interval of the mean difference).
ADC left FL kurtosis
ADC right PL mean
ADC right PL median
ADC_uh right TL mean
ADC_uh right TL median
Dapp left FL kurtosis
Dapp right PL mean
Dapp right PL median
Table 4 Correlations with MMSE score for all parameters.
95% CI a
0.694 - 0.918
0.627 - 0.873
0.718 - 0.932
0.779 - 0.964
0.711 - 0.928
0.775 - 0.962
0.743 - 0.946
Table 5 Comparison of receiver-operating characteristic (ROC) curves.
Table 6 The correlations of ADC, ADC_uh, Dapp and Kapp parameters between the two tests.
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