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Related Experiment Video

Updated: Dec 5, 2025

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[11C]PIB amyloid quantification: effect of reference region selection.

Fiona Heeman1, Janine Hendriks2, Isadora Lopes Alves2

  • 1Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. f.heeman@amsterdamumc.nl.

EJNMMI Research
|October 19, 2020
PubMed
Summary
This summary is machine-generated.

Cerebellar grey matter (GMCB) and whole cerebellum (WCB) are the best reference regions for amyloid-beta PET imaging, showing stable and accurate quantification of amyloid burden. These regions offer reliable performance in longitudinal studies and discrimination of amyloid positivity.

Keywords:
Alzheimer’s diseaseAmyloid PETQuantificationReference regions[11C]PiB

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Area of Science:

  • Neuroimaging
  • Nuclear Medicine
  • Biomarker Discovery

Background:

  • Standard reference region (RR) for amyloid-beta (Aβ) PET is cerebellar grey matter (GMCB).
  • Alternative RRs often lack validation against gold standards.
  • This study validated five common RRs against plasma input-based quantification using GMCB.

Purpose of the Study:

  • To compare the performance of five commonly used reference regions (RRs) against a gold standard plasma input-based quantification method.
  • To evaluate the test-retest variability, longitudinal stability, and ability to discriminate amyloid positivity for each RR.
  • To identify the most reliable RRs for quantifying amyloid burden using [11C]PiB PET.

Main Methods:

  • Retrospective analysis of 13 test-retest and 30 longitudinal subjects (AD, MCI, controls).
  • Dynamic [11C]PiB PET and MRI co-registration, time-activity curve extraction for target regions and RRs (GMCB, WCB, WMBS, WBS, WMES).
  • Comparison of distribution volume ratios (DVRs) and standardized uptake value (SUV) ratios derived using different RRs against a gold standard plasma input model.

Main Results:

  • All tested RRs showed stable test-retest performance (max 5.1% variability); WCB exhibited lower variability.
  • All RRs successfully discriminated between amyloid-positive and amyloid-negative scans, with GMCB and WCB showing the highest effect sizes.
  • Good correlations (r ≥ 0.78) were observed for all RRs with the gold standard, though WMES, WBS, and WMBS showed higher bias.
  • RR SUVs remained stable over 2.6 years, except for WBS and WMBS in the 60-90 min interval.

Conclusions:

  • Cerebellar grey matter (GMCB) and whole cerebellum (WCB) are the optimal reference regions for quantifying amyloid burden with [11C]PiB PET.
  • These regions provide reliable and stable measurements for both cross-sectional and longitudinal analyses.
  • The findings support the use of GMCB and WCB for accurate amyloid PET quantification in clinical and research settings.