TY - JOUR
T1 - 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 Aβ species
AU - Oliveira, Francisco
AU - Leuzy, Antoine
AU - Castelhano, João
AU - Chiotis, Konstantinos
AU - Hasselbalch, Steen Gregers
AU - Rinne, Juha
AU - Mendonça, Alexandre
AU - Otto, Markus
AU - Lleó, Alberto
AU - Santana, Isabel
AU - Johansson, Jarkko
AU - Anderl-Straub, Sarah
AU - Arnim, Christine
AU - Beer, Ambros
AU - Blesa, Rafael
AU - Fortea, Juan
AU - Sanna-Kaisa, Herukka
AU - Portelius, Erik
AU - Pannee, Josef
AU - Zetterberg, Henrik
AU - Blennow, Kaj
AU - Moreira, Ana P
AU - Abrunhosa, Antero
AU - Nordberg, Agneta
AU - Castelo-Branco, Miguel
PY - 2018/1/1
Y1 - 2018/1/1
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 β (Aβ) 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 Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ 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 Aβ 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. Aβ38 and Aβ40 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 Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter.
AB - 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 β (Aβ) 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 Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ 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 Aβ 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. Aβ38 and Aβ40 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 Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter.
KW - Aged
KW - Alzheimer Disease/cerebrospinal fluid
KW - Amyloid beta-Peptides/cerebrospinal fluid
KW - Aniline Compounds
KW - Biomarkers/cerebrospinal fluid
KW - Carbon Radioisotopes
KW - Data Analysis
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Positron-Emission Tomography/methods
KW - Thiazoles
U2 - 10.1016/j.nicl.2018.08.023
DO - 10.1016/j.nicl.2018.08.023
M3 - Journal article
C2 - 30186764
SN - 2213-1582
VL - 20
SP - 603
EP - 610
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
ER -