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Aging and disease    2019, Vol. 10 Issue (5) : 1026-1036     DOI: 10.14336/AD.2018.1129
Orginal Article |
Characterization of Alzheimer’s Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging
Yingnan Xue1, Zhenhua Zhang1, Caiyun Wen1, Huiru Liu1, Suyuan Wang1, Jiance Li1, Qichuan Zhuge2, Weijian Chen1,*, Qiong Ye1,*
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
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Abstract  

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.

Keywords Alzheimer’s Disease      Ultra-high B-values Apparent Diffusion Coefficient      Diffusion Kurtosis Imaging      Apparent Diffusion Coefficient      ADC_uh      DKI     
Corresponding Authors: Chen Weijian,Ye Qiong   
About author:

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 2018   Issue Date: 27 September 2019
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Xue Yingnan
Zhang Zhenhua
Wen Caiyun
Liu Huiru
Wang Suyuan
Li Jiance
Zhuge Qichuan
Chen Weijian
Ye Qiong
Cite this article:   
Xue Yingnan,Zhang Zhenhua,Wen Caiyun, et al. Characterization of Alzheimer’s Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging[J]. Aging and disease, 2019, 10(5): 1026-1036.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2018.1129     OR     http://www.aginganddisease.org/EN/Y2019/V10/I5/1026
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.
ADHCp-value
Number (M/F)11/208/120.774*
Age(years)64.94±8.20556.70±6.2580.000**
MMSE18.48±4.71127.85±1.5650.000**
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 ± SDCVP-value
ADC
right HIP mean (×10-3mm/s)AD0.961±0.1260.1310.008
HC0.874±0.0950.109
right HIP median (×10-3mm/s)AD0.956±0.1160.1220.001
HC0.877±0.0950.109
left CAU skewnessAD0.053±0.55410.4840.013
HC-0.313±0.515-1.645
right LVe skewnessAD0.377±0.8812.3380.000
HC-0.619±0.873-1.410
left FL kurtosisAD2.888±0.6890.2390.036
HC0.254±0.5130.202
right PL mean (×10-3mm/s)AD0.815±0.0910.1110.002
HC0.750±0.0510.068
right PL median (×10-3mm/s)AD0.818±0.0940.1150.003
HC0.754±0.0500.066
ADC_uh
left THA mean (×10-3mm/s)AD0.358±0.0320.0890.047
HC0.336±0.0460.123
left LVe kurtosisAD3.16±0.8000.2530.028
HC2.71±0.6080.224
right TL mean (×10-3mm/s)AD0.274±0.0420.1540.033
HC0.252±0.0290.116
right TL median (×10-3mm/s)AD0.273±0.0450.1650.032
HC0.249±0.0300.120
left TL mean (×10-3mm/s)AD0.276±0.0390.1410.022
HC0.250±0.0380.152
left TL median (×10-3mm/s)AD0.273±0.0380.1380.038
HC0.249±0.0420.170
right CS mean (×10-3mm/s)AD0.273±0.0380.0880.021
HC0.203±0.0150.073
right CS median (×10-3mm/s)AD0.214±0.0190.0890.016
HC0.201±0.0150.074
Table 2  Comparisons of regional diffusion intensity in ADC or ADC_uh between AD and HC group.
Mean±SDCVP-value
DAPP
left FL kurtosisAD3.020±0.7750.2570.030
HC2.620±0.7400.282
right PL mean (×10-3mm/s)AD0.942±0.1050.1120.003
HC0.870±0.0600.069
right PL median (×10-3mm/s)AD0.943±0.1070.1130.004
HC0.870±0.0630.073
KAPP
right THA medianAD0.713±0.0720.1010.046
HC0.754±0.0750.099
right LVe meanAD0.266±0.0490.1850.042
HC0.296±0.0690.233
left LVe meanAD0.263±0.0490.1870.004
HC0.298±0.0440.149
left LVe medianAD0.279±0.0400.1430.006
HC0.308±0.0380.125
right FL kurtosisAD5.950±3.1400.5730.009
HC3.940±2.4600.624
left FL kurtosisAD5.750±3.0100.5240.019
HC4.380±3.2500.742
left TL meanAD0.740±0.1060.1440.009
HC0.816±0.0900.111
left TL medianAD0.754±0.1040.1380.018
HC0.819±0.0860.105
right PL meanAD1.000±0.1390.1380.019
HC1.090±0.1280.117
right PL medianAD0.994±0.1270.1280.015
HC1.090±0.1330.122
left PL meanAD0.949±0.1460.1540.007
HC1.070±0.1420.133
left PL medianAD0.940±0.1430.1520.010
HC1.050±0.1460.139
right CS meanAD1.060±0.1130.1070.011
HC1.150±0.1020.089
right CS medianAD1.040±0.1090.1050.004
HC1.130±0.1040.092
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).
rhop
ADC left FL kurtosis550**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.
AUC95% CI aPb
ADC0.8260.694 - 0.918NL
ADC_uh0.7660.627 - 0.8730.501
DKI0.8470.718 - 0.9320.728
ADC+ADC_uh0.897#0.779 - 0.9640.172
ADC+DKI0.8400.711 - 0.9280.729
ADC_uh+DKI0.8940.775 - 0.9620.284
ADC+ADC_uh+DKI0.8680.743 - 0.9460.416
Table 5  Comparison of receiver-operating characteristic (ROC) curves.
rhop
ADC mean0.7820.000**
ADC median0.7600.000**
ADC skewness0.1940.006*
ADC kurtosis0.2260.001*
ADC_uh mean0.9010.000**
ADC_uh median0.8970.000**
ADC_uh skewness0.1330.061
ADC_uh kurtosis0.0580.412
Dapp mean0.7100.000**
Dapp median0.6750.000**
Dapp skewness0.1690.017*
Dapp kurtosis0.1420.046*
Kapp mean0.9290.000**
Kapp median0.9340.000**
Kapp skewness0.1930.006*
Kapp kurtosis0.2780.000**
Table 6  The correlations of ADC, ADC_uh, Dapp and Kapp parameters between the two tests.
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