Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2020:25:102146.
doi: 10.1016/j.nicl.2019.102146. Epub 2019 Dec 23.

Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment

Sudipto Dolui  1 , Zhengjun Li  1 , Ilya M Nasrallah  1 , John A Detre  2 , David A Wolk  3
Affiliations
Comparative Study

Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment

Sudipto Dolui et al. Neuroimage Clin. 2020.

Abstract

Neurodegenerative biomarkers support diagnosis and measurement of disease progression in the Alzheimer's disease (AD) continuum. 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET), which measures glucose metabolism, is one of the most commonly used biomarkers of neurodegeneration, but is expensive and requires exposure to ionizing radiation. Arterial Spin Labeled (ASL) perfusion Magnetic Resonance Imaging (MRI) provides non invasive quantification of cerebral blood flow (CBF), which is believed to be tightly coupled to glucose metabolism. Here we aimed to compare the performances of ASL derived CBF and 18F-FDG-PET derived standardized uptake value ratio (SUVR) in discriminating patients with mild cognitive impairment (MCI) from older Controls. 2D pseudo continuous ASL and 18F-FDG-PET data with adequate scan quality from 50 MCI study participants (age=73.0 ± 7.0 years, 16 female) and 35 older controls (age=70.2 ± 6.9 years, 20 female), acquired in close temporal proximity, usually on the same day, were considered for this study. We assessed Control-patient group differences both at voxel level and within a priori regions of interest (ROIs). We also compared their area under receiver operating characteristic curves (AUC) with mean CBF or SUVR in a priori selected posterior cingulate cortex (PCC). CBF and 18F-FDG-PET showed abnormalities in similar areas, particularly in medial temporoparietal regions, consistent with the typically observed pattern of prodromal AD. The hypoperfusion pattern with relative CBF (obtained by normalizing voxel CBF values with mean CBF in putamen) was more localized than with absolute CBF. Pearson's correlation coefficients between the T-scores corresponding to the group-differences obtained with 18F-FDG-PET SUVR and absolute and relative ASL CBF were 0.46 and 0.43 (p<0.001), respectively. ROI analyses were also consistent, with the strongest differences observed in PCC (p<0.01). 18F-FDG-PET SUVR, absolute and relative CBF in the PCC ROI demonstrated moderate and similar discriminatory power in predicting MCI status with AUC of 0.71 ± 0.12, 0.77 ± 0.12 and 0.74 ± 0.13, respectively. In conclusion, ASL CBF may be a reasonable, less expensive and safer substitute for 18F-FDG-PET in clinical research.

Keywords: (18)F-Fluorodeoxyglucose positron emission tomography; Alzheimer's disease; Arterial spin labeling; Hypometabolism; Hypoperfusion; Mild cognitive impairment.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest We believe there is no conflict of interest related to this work. However we disclose here that Dr. Wolk received personal fees for consultation from GE Healthcare, Merck, Eli Lilly, and Jannsen during the conduct of the study; and received grants from Avid Radiopharmaceuticals, Eli Lilly, Merck, Functional Neuromodulation, and Biogen outside the submitted work. Dr. Nasrallah received a grant from Avid Radiopharmaceuticals/Eli Lilly outside the submitted work.

Figures

Fig 1
Fig. 1
Triaxial view of (left to right) average maps of the controls, MCI patients, and their differences for Absolute CBF (row 1), Relative CBF (row 2), and 18F-FDG-PET SUVR (row 3).
Fig 2
Fig. 2
Regions showing significant voxel level group differences between MCI and controls for A) 18F-FDG-PET SUVR relative to uptake in pons and cerebellar vermis; B) absolute ASL-CBF; C) relative ASL-CBF relative to Putamen. Non-parametric two sample T tests were conducted with “randomise” tool of FSL toolbox, and the results were thresholded with p<0.05 threshold-free cluster enhancement (TFCE) family-wise error (FWE) rate controlled. Hot color indicates lower in MCI than Control and cold color indicates higher in MCI than control.
Fig 3
Fig. 3
Overlap of regions showing statistically significant group differences between MCI and control groups using 18F-FDG-PET SUVR with Absolute (Left) and Relative CBF (Right); red indicates regions with group difference shown by ASL-CBF (absolute or relative), blue that with 18F-FDG-PET SUVR and green showing the overlap of the two modalities. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig 4
Fig. 4
Box plots with individual data points for group differences between MCI and normal controls in selected ROIs for (left) 18F-FDG-PET SUVR relative to pons and cerebellar vermis uptake; (middle) absolute ASL-CBF; (right) relative ASL-CBF normalized to putamen. Abbreviations: GM: gray matter, PCC: posterior cingulate cortex; HIPP: hippocampus; meta-ROI: composite ROI sensitive to AD metabolic changes; M1: precentral cortex. Significant p values (FDR corrected) are marked with *: p<0.05; **: p<0.01; ***: p<0.001.
Fig 5
Fig. 5
Receiver Operating Characteristic (ROC) curves in classifying MCI patients and older controls using 18F-FDG-PET SUVR, absolute and relative CBF.
See this image and copyright information in PMC

References

    1. Albert M.S., DeKosky S.T., Dickson D., Dubois B., Feldman H.H., Fox N.C., Gamst A., Holtzman D.M., Jagust W.J., Petersen R.C., Snyder P.J., Carrillo M.C., Thies B., Phelps C.H. The diagnosis of mild cognitive impairment due to alzheimer's disease: recommendations from the national institute on aging-alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270–279. - PMC - PubMed
    1. Alsop D.C., Detre J.A., Golay X., Gunther M., Hendrikse J., Hernandez-Garcia L., Lu H., Macintosh B.J., Parkes L.M., Smits M., van Osch M.J., Wang D.J., Wong E.C., Zaharchuk G. Recommended implementation of arterial spin-labeled perfusion mri for clinical applications: a consensus of the ismrm perfusion study group and the european consortium for asl in dementia. Magn. Reson. Med. 2015;73:102–116. - PMC - PubMed
    1. Avants B.B., Tustison N.J., Song G., Cook P.A., Klein A., Gee J.C. A reproducible evaluation of ANTs similarity metric performance in brain image registration. Neuroimage. 2011;54:2033–2044. - PMC - PubMed
    1. Bailly M., Destrieux C., Hommet C., Mondon K., Cottier J.P., Beaufils E., Vierron E., Vercouillie J., Ibazizene M., Voisin T., Payoux P., Barre L., Camus V., Guilloteau D., Ribeiro M.J. Precuneus and cingulate cortex atrophy and hypometabolism in patients with alzheimer's disease and mild cognitive impairment: mri and (18)F-FDG pet quantitative analysis using freesurfer. Biomed. Res. Int. 2015;2015 - PMC - PubMed
    1. Chen Y., Wolk D.A., Reddin J.S., Korczykowski M., Martinez P.M., Musiek E.S., Newberg A.B., Julin P., Arnold S.E., Greenberg J.H., Detre J.A. Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology. 2011;77:1977–1985. - PMC - PubMed

Publication types

MeSH terms