TY - JOUR
T1 - White matter reference region in PET studies of 11C-Pittsburgh compound B uptake
T2 - Effects of age and amyloid-β deposition
AU - Lowe, Val J.
AU - Lundt, Emily S.
AU - Senjem, Matthew L.
AU - Schwarz, Christopher G.
AU - Min, Hoon Ki
AU - Przybelski, Scott A.
AU - Kantarci, Kejal
AU - Knopman, David
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
N1 - Funding Information:
This work was supported by NIH grants P50 AG16574, U01 AG06786, R01 AG11378, and R01 AG041851; the Elsie and Marvin Dekelboum Family Foundation; GHR Foundation; and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. Dr. Lowe is a consultant for Bayer Schering Pharma and Piramal Imaging Inc. and receives research support from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals. Dr. Knopman serves on a Data Safety Monitoring Board for the DIAN study and is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the Alzheimer’s Disease Cooperative Study. Dr. Petersen serves on scientific advisory boards for Pfizer, Inc., Janssen Alzheimer Immunotherapy, Elan Pharmaceuticals, and GE Healthcare. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh compound B (11C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n 5 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a crosssectional study of single-scan PET imaging in CU subjects (n 5 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM 11C-PiB. These correlations should be considered when using WM for normalization in 11C-PiB PET studies. The cerebellar crus11Crus2 showed no increase with age and cerebellar GM1WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.
AB - Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh compound B (11C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n 5 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a crosssectional study of single-scan PET imaging in CU subjects (n 5 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM 11C-PiB. These correlations should be considered when using WM for normalization in 11C-PiB PET studies. The cerebellar crus11Crus2 showed no increase with age and cerebellar GM1WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.
KW - 11C-PiB
KW - AD
KW - Amyloid-β
KW - PET
KW - White matter
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U2 - 10.2967/jnumed.117.204271
DO - 10.2967/jnumed.117.204271
M3 - Article
C2 - 29674420
AN - SCOPUS:85054071369
SN - 0161-5505
VL - 59
SP - 1583
EP - 1589
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 10
ER -