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.
Jean-Marc Burgunder is currently a visiting professor at Sichuan University (Chengdu), Central South University (Changsha) and Sun Yat Sen University (Guangzhou) in China.
Just Accepted Date: 03 December 2018Issue Date: 27 September 2019
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.
AD
HC
p-value
Number (M/F)
11/20
8/12
0.774*
Age(years)
64.94±8.205
56.70±6.258
0.000**
MMSE
18.48±4.711
27.85±1.565
0.000**
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
CV
P-value
ADC
right HIP mean (×10-3mm/s)
AD
0.961±0.126
0.131
0.008
HC
0.874±0.095
0.109
right HIP median (×10-3mm/s)
AD
0.956±0.116
0.122
0.001
HC
0.877±0.095
0.109
left CAU skewness
AD
0.053±0.554
10.484
0.013
HC
-0.313±0.515
-1.645
right LVe skewness
AD
0.377±0.881
2.338
0.000
HC
-0.619±0.873
-1.410
left FL kurtosis
AD
2.888±0.689
0.239
0.036
HC
0.254±0.513
0.202
right PL mean (×10-3mm/s)
AD
0.815±0.091
0.111
0.002
HC
0.750±0.051
0.068
right PL median (×10-3mm/s)
AD
0.818±0.094
0.115
0.003
HC
0.754±0.050
0.066
ADC_uh
left THA mean (×10-3mm/s)
AD
0.358±0.032
0.089
0.047
HC
0.336±0.046
0.123
left LVe kurtosis
AD
3.16±0.800
0.253
0.028
HC
2.71±0.608
0.224
right TL mean (×10-3mm/s)
AD
0.274±0.042
0.154
0.033
HC
0.252±0.029
0.116
right TL median (×10-3mm/s)
AD
0.273±0.045
0.165
0.032
HC
0.249±0.030
0.120
left TL mean (×10-3mm/s)
AD
0.276±0.039
0.141
0.022
HC
0.250±0.038
0.152
left TL median (×10-3mm/s)
AD
0.273±0.038
0.138
0.038
HC
0.249±0.042
0.170
right CS mean (×10-3mm/s)
AD
0.273±0.038
0.088
0.021
HC
0.203±0.015
0.073
right CS median (×10-3mm/s)
AD
0.214±0.019
0.089
0.016
HC
0.201±0.015
0.074
Table 2 Comparisons of regional diffusion intensity in ADC or ADC_uh between AD and HC group.
Mean±SD
CV
P-value
DAPP
left FL kurtosis
AD
3.020±0.775
0.257
0.030
HC
2.620±0.740
0.282
right PL mean (×10-3mm/s)
AD
0.942±0.105
0.112
0.003
HC
0.870±0.060
0.069
right PL median (×10-3mm/s)
AD
0.943±0.107
0.113
0.004
HC
0.870±0.063
0.073
KAPP
right THA median
AD
0.713±0.072
0.101
0.046
HC
0.754±0.075
0.099
right LVe mean
AD
0.266±0.049
0.185
0.042
HC
0.296±0.069
0.233
left LVe mean
AD
0.263±0.049
0.187
0.004
HC
0.298±0.044
0.149
left LVe median
AD
0.279±0.040
0.143
0.006
HC
0.308±0.038
0.125
right FL kurtosis
AD
5.950±3.140
0.573
0.009
HC
3.940±2.460
0.624
left FL kurtosis
AD
5.750±3.010
0.524
0.019
HC
4.380±3.250
0.742
left TL mean
AD
0.740±0.106
0.144
0.009
HC
0.816±0.090
0.111
left TL median
AD
0.754±0.104
0.138
0.018
HC
0.819±0.086
0.105
right PL mean
AD
1.000±0.139
0.138
0.019
HC
1.090±0.128
0.117
right PL median
AD
0.994±0.127
0.128
0.015
HC
1.090±0.133
0.122
left PL mean
AD
0.949±0.146
0.154
0.007
HC
1.070±0.142
0.133
left PL median
AD
0.940±0.143
0.152
0.010
HC
1.050±0.146
0.139
right CS mean
AD
1.060±0.113
0.107
0.011
HC
1.150±0.102
0.089
right CS median
AD
1.040±0.109
0.105
0.004
HC
1.130±0.104
0.092
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).
rho
p
ADC left FL kurtosis
550**
0.001
ADC right PL mean
-.368*
0.042
ADC right PL median
-.356*
0.049
ADC_uh right TL mean
-.420*
0.019
ADC_uh right TL median
-.386*
0.032
Dapp left FL kurtosis
.546**
0.001
Dapp right PL mean
-.416*
0.020
Dapp right PL median
-.403*
0.024
Table 4 Correlations with MMSE score for all parameters.
AUC
95% CI a
Pb
ADC
0.826
0.694 - 0.918
NL
ADC_uh
0.766
0.627 - 0.873
0.501
DKI
0.847
0.718 - 0.932
0.728
ADC+ADC_uh
0.897#
0.779 - 0.964
0.172
ADC+DKI
0.840
0.711 - 0.928
0.729
ADC_uh+DKI
0.894
0.775 - 0.962
0.284
ADC+ADC_uh+DKI
0.868
0.743 - 0.946
0.416
Table 5 Comparison of receiver-operating characteristic (ROC) curves.
rho
p
ADC mean
0.782
0.000**
ADC median
0.760
0.000**
ADC skewness
0.194
0.006*
ADC kurtosis
0.226
0.001*
ADC_uh mean
0.901
0.000**
ADC_uh median
0.897
0.000**
ADC_uh skewness
0.133
0.061
ADC_uh kurtosis
0.058
0.412
Dapp mean
0.710
0.000**
Dapp median
0.675
0.000**
Dapp skewness
0.169
0.017*
Dapp kurtosis
0.142
0.046*
Kapp mean
0.929
0.000**
Kapp median
0.934
0.000**
Kapp skewness
0.193
0.006*
Kapp kurtosis
0.278
0.000**
Table 6 The correlations of ADC, ADC_uh, Dapp and Kapp parameters between the two tests.
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