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

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; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1186/s13195-016-0172-3

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

Journal article

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

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 and Alzheimer’s Disease Neuroimaging Initiative

Alzheimer's research & therapy, Vol.8(1), 2

01/15/2016

DOI: 10.1186/s13195-016-0172-3

PMCID: PMC4714472

PMID: 26768154

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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) Aβ1–42 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 Aβ1–42, 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 Aβ1–42 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: Subtitle: Reference tissue normalization in longitudinal 18F-florbetapir positron emission tomography of late mild cognitive impairment
Creators: Sepideh Shokouhi - Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232-2310 USA
John W Mckay - Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232-2310 USA
Suzanne L Baker - Center of Functional Imaging, Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720 USA
Hakmook Kang - Department of Biostatistics, Vanderbilt University, 2525 West End Avenue, 11th Floor, Suite 11000, Nashville, TN 37203-1738 USA
Aaron B Brill - Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232-2310 USA
Harry E Gwirtsman - Department of Psychiatry, Vanderbilt University, 1601 23rd Avenue South, Nashville, TN 37212 USA
William R Riddle - Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232-2310 USA
Daniel O Claassen - Department of Neurology, Vanderbilt University, A-0118 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232-2551 USA
Baxter P Rogers - Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 1161 21st Avenue South, Medical Center North, AA-1105, Nashville, TN 37232-2310 USA
Alzheimer’s Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Alzheimer's research & therapy, Vol.8(1), 2
DOI: 10.1186/s13195-016-0172-3
PMID: 26768154
PMCID: PMC4714472
NLM abbreviation: Alzheimers Res Ther
ISSN: 1758-9193
eISSN: 1758-9193
Publisher: BioMed Central; London
Grant note: R00 EB 009106 / ; K23 NS080988 / ;
Language: English
Date published: 01/15/2016
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051598202771

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