White matter reference region in PET studies of 11C-Pittsburgh compound B uptake: Effects of age and amyloid-β deposition

Val Lowe, Emily S. Lundt, Matthew L. Senjem, Christopher Schwarz, Hoon Ki Min, Scott A. Przybelski, Kejal M Kantarci, David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1583-1589
Number of pages7
JournalJournal of Nuclear Medicine
Volume59
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Amyloid
Longitudinal Studies
White Matter
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Dementia
Alzheimer Disease
Cross-Sectional Studies
Positron-Emission Tomography
Disease Progression

Keywords

  • 11C-PiB
  • AD
  • Amyloid-β
  • PET
  • White matter

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

White matter reference region in PET studies of 11C-Pittsburgh compound B uptake : Effects of age and amyloid-β deposition. / Lowe, Val; Lundt, Emily S.; Senjem, Matthew L.; Schwarz, Christopher; Min, Hoon Ki; Przybelski, Scott A.; Kantarci, Kejal M; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.

In: Journal of Nuclear Medicine, Vol. 59, No. 10, 01.10.2018, p. 1583-1589.

Research output: Contribution to journalArticle

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abstract = "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.",
keywords = "11C-PiB, AD, Amyloid-β, PET, White matter",
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AU - Lowe, Val

AU - Lundt, Emily S.

AU - Senjem, Matthew L.

AU - Schwarz, Christopher

AU - Min, Hoon Ki

AU - Przybelski, Scott A.

AU - Kantarci, Kejal M

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

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