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Open Access 01-12-2016 | Research

Reference tissue normalization in longitudinal ¹⁸F-florbetapir positron emission tomography of late mild cognitive impairment

Authors: Sepideh Shokouhi, John W. Mckay, Suzanne L. Baker, Hakmook Kang, Aaron B. Brill, Harry E. Gwirtsman, William R. Riddle, Daniel O. Claassen, Baxter P. Rogers, for the Alzheimer’s Disease Neuroimaging Initiative

Published in: Alzheimer's Research & Therapy | Issue 1/2016

Abstract

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-β (Aβ) 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 ¹⁸F-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 ¹⁸F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ_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 (wS₂)—to capture potentially more subtle changes in Aβ-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 Aβ_1–42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS₂ values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ_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 ¹⁸F-florbetapir uptake in longitudinal studies.

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Title: Reference tissue normalization in longitudinal 18F-florbetapir positron emission tomography of late mild cognitive impairment
Authors: Sepideh Shokouhi
John W. Mckay
Suzanne L. Baker
Hakmook Kang
Aaron B. Brill
Harry E. Gwirtsman
William R. Riddle
Daniel O. Claassen
Baxter P. Rogers
for the Alzheimer’s Disease Neuroimaging Initiative
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2016
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-016-0172-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Reference tissue normalization in longitudinal ¹⁸F-florbetapir positron emission tomography of late mild cognitive impairment

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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