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
. 2022 May;43(7):2121-2133.
doi: 10.1002/hbm.25774. Epub 2022 Feb 15.

Tracer-specific reference tissues selection improves detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes in Alzheimer's disease

Yanxiao Li  1   2 , Yee Ling Ng  1 , Manish D Paranjpe  3 , Qi Ge  1 , Fengyun Gu  1   4 , Panlong Li  5 , Shaozhen Yan  6 , Jie Lu  6 , Xiuying Wang  2 , Yun Zhou  1 ; for the Alzheimer's Disease Neuroimaging Initiative
Affiliations

Tracer-specific reference tissues selection improves detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes in Alzheimer's disease

Yanxiao Li et al. Hum Brain Mapp. 2022 May.

Abstract

This study sought to identify a reference tissue-based quantification approach for improving the statistical power in detecting changes in brain glucose metabolism, amyloid, and tau deposition in Alzheimer's disease studies. A total of 794, 906, and 903 scans were included for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir, respectively. Positron emission tomography (PET) and T1-weighted images of participants were collected from the Alzheimer's disease Neuroimaging Initiative database, followed by partial volume correction. The standardized uptake value ratios (SUVRs) calculated from the cerebellum gray matter, centrum semiovale, and pons were evaluated at both region of interest (ROI) and voxelwise levels. The statistical power of reference tissues in detecting longitudinal SUVR changes was assessed via paired t-test. In cross-sectional analysis, the impact of reference tissue-based SUVR differences between cognitively normal and cognitively impaired groups was evaluated by effect sizes Cohen's d and two sample t-test adjusted by age, sex, and education levels. The average ROI t values of pons were 86.62 and 38.40% higher than that of centrum semiovale and cerebellum gray matter in detecting glucose metabolism decreases, while the centrum semiovale reference tissue-based SUVR provided higher t values for the detection of amyloid and tau deposition increases. The three reference tissues generated comparable d images for 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir and comparable t maps for 18 F-florbetapir and 18 F-flortaucipir, but pons-based t map showed superior performance in 18 F-FDG. In conclusion, the tracer-specific reference tissue improved the detection of 18 F-FDG, 18 F-florbetapir, and 18 F-flortaucipir PET SUVR changes, which helps the early diagnosis, monitoring of disease progression, and therapeutic response in Alzheimer's disease.

Keywords: 18F-FDG; 18F-florbetapir; 18F-flortaucipir; Alzheimer's disease; reference tissue.

PubMed Disclaimer

Conflict of interest statement

The authors have declared no conflicts of interest for this article.

Figures

FIGURE 1
FIGURE 1
Paired statistical t map of longitudinal (mean follow‐up period: 63.42 ± 27.15 months, n = 53) 18F‐FDG SUVR changes in participants with cognitive decline. The SUVR was calculated for reference tissue cerebellum GM, centrum semiovale, and pons, respectively
FIGURE 2
FIGURE 2
Statistical t values of ROI‐based longitudinal 18F‐FDG SUVR changes in subjects with cognitive decline. Statistical p values indicate *p < .05, **p < .001, ***p < .0001. ACC, anterior cingulate; Amy, amygdala; Caud, Caudate; EC, entorhinal cortex; Hip, hippocampus; InfT, inferior temporal; LatT, lateral temporal; MT, medial temporal; OrbF, orbital frontal; Par, parietal; PCC, posterior cingulate; PHip, parahippocampal gyrus; PPrC, posterior precuneus; PreF, prefrontal; SupF, superior frontal
FIGURE 3
FIGURE 3
Paired statistical t map of longitudinal (mean follow‐up period: 57.05 ± 18.75 months, n = 55) 18F‐florbetapir SUVR changes in participants with cognitive decline. The SUVR was calculated for reference tissue cerebellum GM, centrum semiovale, and pons, respectively
FIGURE 4
FIGURE 4
Statistical t values of ROI‐based longitudinal 18F‐florbetapir SUVR changes in subjects with cognitive decline. Statistical p values indicate *p < .05, **p < .001, ***p < .0001. ACC, anterior cingulate; InfT, inferior temporal; LatT, lateral temporal; Occ, occipital; OrbF, orbital frontal; Par, parietal; PCC, posterior cingulate; PPrC, posterior precuneus; PreF, prefrontal; SupF, superior frontal
FIGURE 5
FIGURE 5
Paired statistical t map of longitudinal (mean follow‐up period: 19.88 ± 8.03 months, n = 20) 18F‐flortaucipir SUVR changes in participants with cognitive decline. The SUVR was calculated for reference tissue cerebellum GM, centrum semiovale, and pons, respectively
FIGURE 6
FIGURE 6
Statistical t values of ROI‐based longitudinal 18F‐flortaucipir SUVR changes in subjects with cognitive decline. Statistical p values indicate *p < .05, **p < .001, ***p < .0001
FIGURE 7
FIGURE 7
Statistical Cohen's d images for SUVR differences between cognitively normal (CN) and impaired (CI) groups in 18F‐FDG (a), 18F‐florbetapir (b), and 18F‐flortaucipir (c) PET studies when using cerebellum GM, centrum semiovale, and pons as reference tissue. The SUVR was calculated for reference tissue cerebellum GM, centrum semiovale, and pons, respectively
FIGURE 8
FIGURE 8
Statistical t images for SUVR differences between cognitively normal (CN) and impaired (CI) groups in 18F‐FDG (a), 18F‐florbetapir (b), and 18F‐flortaucipir (c) PET studies when using cerebellum GM, centrum semiovale, and pons as reference tissue. The SUVR was calculated for reference tissue cerebellum GM, centrum semiovale, and pons, respectively
See this image and copyright information in PMC

References

    1. Alexander, G. E. , Chen, K. , Pietrini, P. , Rapoport, S. I. , & Reiman, E. M. (2002). Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies. The American Journal of Psychiatry, 159(5), 738–745. 10.1176/appi.ajp.159.5.738 - DOI - PubMed
    1. Baker, S. L. , Lockhart, S. N. , Price, J. C. , He, M. , Huesman, R. H. , Schonhaut, D. , & Jagust, W. J. (2017). Reference tissue‐based kinetic evaluation of 18F‐AV‐1451 for tau imaging. Journal of Nuclear Medicine, 58(2), 332–338. - PMC - PubMed
    1. Barret, O. , Alagille, D. , Sanabria, S. , Comley, R. A. , Weimer, R. M. , Borroni, E. , & Morley, T. (2017). Kinetic modeling of the tau PET tracer 18F‐AV‐1451 in human healthy volunteers and Alzheimer disease subjects. Journal of Nuclear Medicine, 58(7), 1124–1131. - PubMed
    1. Bilgel, M. , Beason‐Held, L. , An, Y. , Zhou, Y. , Wong, D. F. , & Resnick, S. M. (2020). Longitudinal evaluation of surrogates of regional cerebral blood flow computed from dynamic amyloid PET imaging. Journal of Cerebral Blood Flow and Metabolism, 40(2), 288–297. 10.1177/0271678X19830537 - DOI - PMC - PubMed
    1. Blautzik, J. , Brendel, M. , Sauerbeck, J. , Kotz, S. , Scheiwein, F. , Bartenstein, P. , & Alzheimer's Disease Neuroimaging Initiative . (2017). Reference region selection and the association between the rate of amyloid accumulation over time and the baseline amyloid burden. European Journal of Nuclear Medicine and Molecular Imaging, 44(8), 1364–1374. 10.1007/s00259-017-3666-8 - DOI - PubMed

Publication types