TY  - JOUR
N2  - Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid ? (A?) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of A?38, A?40 and A?42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF A? concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than A? concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. A?38 and A?40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with A?42, the A?42/A?40 or A?42/A?38 ratios were found compared to normalization based on cerebellar gray matter.
ID  - discovery10056831
UR  - http://dx.doi.org/10.1016/j.nicl.2018.08.023
SN  - 2213-1582
JF  - NeuroImage Clinical
A1  - Oliveira, F
A1  - Leuzy, A
A1  - Castelhano, J
A1  - Chiotis, K
A1  - Hasselbalch, SG
A1  - Rinne, J
A1  - Mendonça, A
A1  - Otto, M
A1  - Lleó, A
A1  - Santana, I
A1  - Johansson, J
A1  - Anderl-Straub, S
A1  - Arnim, C
A1  - Beer, A
A1  - Blesa, R
A1  - Fortea, J
A1  - Sanna-Kaisa, H
A1  - Portelius, E
A1  - Pannee, J
A1  - Zetterberg, H
A1  - Blennow, K
A1  - Moreira, AP
A1  - Abrunhosa, A
A1  - Nordberg, A
A1  - Castelo-Branco, M
TI  - Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of A? species
Y1  - 2018///
AV  - public
VL  - 20
SP  - 603
EP  - 610
N1  - © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
ER  -