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Potential Diagnostic Applications of Multi-Delay Arterial Spin Labeling in Early Alzheimer’s Disease: The Chinese Imaging, Biomarkers, and Lifestyle Study

Sun, Mengfan; Wang, Yan Li; Li, Runzhi; Jiang, Jiwei; Zhang, Yanling; Li, Wenyi; Zhang, Yuan; Jia, Ziyan; Chappell, Michael; Xu, Jun


Mengfan Sun

Yan Li Wang

Runzhi Li

Jiwei Jiang

Yanling Zhang

Wenyi Li

Yuan Zhang

Ziyan Jia

Jun Xu


Background: Cerebral blood flow (CBF) alterations are involved in the onset and progression of Alzheimer’s disease (AD) and can be a potential biomarker. However, CBF measured by single-delay arterial spin labeling (ASL) for discrimination of mild cognitive impairment (MCI, an early stage of AD) was lack of accuracy. Multi-delay ASL can not only provide CBF quantification but also provide arterial transit time (ATT). Unfortunately, the technique was scarcely applied to the diagnosis of AD. Here, we detected the utility of ASL with 1-delay and 7-delay in ten regions of interest (ROIs) to identify MCI and AD. Materials and Methods: Pseudocontinuous ASL (pCASL) MRI was acquired on a 3T GE scanner in adults from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Study of AD cohort, including 26 normal cognition (NC), 37 MCI, and 39 AD. Receiver operating characteristic (ROC) analyses with 1-delay and 7-delay ASL were performed for the identification of MCI and AD. The DeLong test was used to compare ROC curves. Results: For CBF of 1-delay or 7-delay the AUCs showed moderate-high performance for the AD/NC and AD/MCI comparisons (AUC = 0.83∼0.96) (p < 0.001). CBF of 1-delay performed poorly in MCI/NC comparison (AUC = 0.69) (p < 0.001), but CBF of 7-delay fared well with an AUC of 0.79 (p < 0.001). The combination of CBF and ATT of 7-delay showed higher performance for AD/NC, AD/MCI, and MCI/NC comparisons with AUCs of 0.96, 0.89, and 0.89, respectively (p < 0.001). Furthermore, combination of CBF, ATT, sex, age, APOE ε4, and education improved further the accuracy (p < 0.001). In subgroups analyses, there were no significant differences in CBF of 7-delay ASL for identification of AD or MCI between age subgroups (p > 0.05). Conclusion: The combination of CBF and ATT with 7-delay ASL showed higher performance for identification of MCI than CBF of 1-delay, when adding to sex, age, APOE ε4 carrier status, and education years, the diagnostic performance was further increased, presenting a potential imaging biomarker in early AD.


Sun, M., Wang, Y. L., Li, R., Jiang, J., Zhang, Y., Li, W., …Xu, J. (2022). Potential Diagnostic Applications of Multi-Delay Arterial Spin Labeling in Early Alzheimer’s Disease: The Chinese Imaging, Biomarkers, and Lifestyle Study. Frontiers in Neuroscience, 16, Article 934471.

Journal Article Type Article
Acceptance Date Jun 21, 2022
Online Publication Date Jul 22, 2022
Publication Date Jul 22, 2022
Deposit Date Sep 12, 2022
Publicly Available Date Sep 13, 2022
Journal Frontiers in Neuroscience
Print ISSN 1662-4548
Electronic ISSN 1662-453X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 16
Article Number 934471
Keywords mild cognitive impairment, arterial transit time, diagnosis, multi-delay arterial spin labeling, Alzheimer’s disease, cerebral blood flow
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