Journal
ALZHEIMERS RESEARCH & THERAPY
Volume 8, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13195-016-0172-3
Keywords
-
Categories
Funding
- National Institutes of Health [NIH] [U01 AG024904]
- U.S. Department of Defense [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb
- CereSpir, Inc.
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- NIH [R00 EB009106, K23 NS080988]
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Background: Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-beta (A beta) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest F-18-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. Methods: We calculated the correlation between F-18-florbetapir PET and concurrent cerebrospinal fluid (CSF) A beta(1-42) levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS(2))-to capture potentially more subtle changes in A beta-PET data. Results: Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF A beta(1-42), while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS(2) values were associated with the lowest coefficient of variation and highest inverse correlation to CSF A beta(1-42) levels across all time points and reference regions, including the cerebellar gray matter. Conclusions: The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical F-18-florbetapir uptake in longitudinal studies.
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