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Title: | 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 | Authors: | Oliveira, Francisco Leuzy, Antoine Castelhano, J. Chiotis, Konstantinos Hasselbalch, Steen Gregers Rinne, Juha Mendonça, Alexandre de Otto, Markus Lleó, Alberto Santana, Isabel Johansson, Jarkko Anderl-Straub, Sarah Arnim, Christine Beer, Ambros Blesa, Rafael Fortea, Juan Sanna-Kaisa, Herukka Portelius, Erik Pannee, Josef Zetterberg, Henrik Blennow, Kaj Moreira, Ana P. Abrunhosa, Antero Nordberg, Agneta Castelo-Branco, Miguel |
Issue Date: | 2018 | Publisher: | Elsevier | Serial title, monograph or event: | NeuroImage: Clinical | Volume: | 20 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/107793 | ISSN: | 22131582 | DOI: | 10.1016/j.nicl.2018.08.023 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D ICNAS - Artigos em Revistas Internacionais I&D CIBIT - Artigos em Revistas Internacionais |
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