A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease

Meng Li; Tianjia Zhu; Yan Kang; Shouliang Qi

doi:10.3389/fnagi.2024.1345251

A 3D pseudo-continuous arterial spin labeling study of altered cerebral blood flow correlation networks in mild cognitive impairment and Alzheimer's disease

Front Aging Neurosci. 2024 Apr 24:16:1345251. doi: 10.3389/fnagi.2024.1345251. eCollection 2024.

Authors

Meng Li^{1

2}, Tianjia Zhu^{3

4}, Yan Kang⁵, Shouliang Qi^{1

6}

Affiliations

¹ College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.
² Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States.
³ Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
⁴ Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, United States.
⁵ College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen, China.
⁶ Key Laboratory of Intelligent Computing in Medical Image, Ministry of Education, Northeastern University, Shenyang, China.

Abstract

Objective: To investigate the abnormalities of the three-dimensional pseudo-continuous arterial spin labeling (3D PCASL) based cerebral blood flow (CBF) correlation networks in mild cognitive impairment (MCI) and Alzheimer's disease (AD).

Methods: 3D PCASL images of 53 cognitive normal (CN) subjects, 43 subjects with MCI, and 30 subjects with AD were acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Whole-brain CBF maps were calculated using PCASL and proton density-weighted images (PDWI). The 246 regional CBF values, including the cortex and subcortex, were obtained after registering the Brainnetome Atlas to the individual CBF maps. The Pearson correlation coefficient between every two regions across subjects was calculated to construct the CBF correlation network. Then the topologies of CBF networks with regard to global properties (global network efficiency, clustering coefficient, characteristic path length, and small-world properties), hub regions, nodal properties (betweenness centrality, BC), and connections were compared among CN, MCI, and AD. Significant changes in the global and nodal properties were observed in the permutation tests, and connections with significant differences survived after the z-statistic and false discovery rate (FDR) correction.

Results: The CBF correlation networks of CN, MCI, and AD all showed small-world properties. Compared with CN, global efficiency decreased significantly in AD. Significant differences in nodal properties and a loss of hub regions are noted in the middle temporal lobe in both MCI and AD. In the frontal lobe, BC is reduced in MCI while it is increased in the occipital lobe in AD. The identified altered hub regions with significant differences in MCI and AD were mainly distributed in the hippocampus and entorhinal cortex. In addition, disrupted hub regions in AD with significantly decreased connections were mainly found in the precuneus/posterior cingulate cortex (PCC) and hippocampus-cortical cortex.

Conclusions: Noninvasive 3D PCASL-based CBF correlation networks are capable of showing changes in topological organization in subjects with MCI and AD, and the observed disruption in the topological organization may underlie cognitive decline in MCI and AD.

Keywords: Alzheimer's disease; arterial spin labeling; brain connectivity; cerebral blood flow; mild cognitive impairment.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Fundamental Research Funds for the Central Universities N2324004-13 and the Natural Science Foundation of Liaoning Province 2020-BS-049. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI was funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.