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

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

doi:10.3389/fnins.2022.934471

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

Front Neurosci. 2022 Jul 22:16:934471. doi: 10.3389/fnins.2022.934471. eCollection 2022.

Authors

Mengfan Sun¹, Yan-Li Wang^{1

2}, Runzhi Li¹, Jiwei Jiang¹, Yanling Zhang³, Wenyi Li¹, Yuan Zhang¹, Ziyan Jia¹, Michael Chappell^{4

5}, Jun Xu^{1

2}

Affiliations

¹ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Mental Health and Clinical Neurosciences and Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
⁵ Nottingham Biomedical Research Centre, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom.

Abstract

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.

Keywords: Alzheimer’s disease; arterial transit time; cerebral blood flow; diagnosis; mild cognitive impairment; multi-delay arterial spin labeling.