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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

2018; Elsevier BV; Volume: 20; Linguagem: Inglês

10.1016/j.nicl.2018.08.023

2213-1582

Francisco P. M. Oliveira, Antoine Leuzy, João Castelhano, Konstantinos Chiotis, Steen Gregers Hasselbalch, Juha O. Rinne, Alexandre de Mendonça, Markus Otto, Alberto Lleó, Isabel Santana, Jarkko Johansson, Sarah Anderl‐Straub, Christine A. F. Von Arnim, Ambros J. Beer, Rafael Blesa, Juan Fortea, Sanna‐Kaisa Herukka, Erik Portelius, Josef Pannee, Henrik Zetterberg, Kaj Blennow, Ana Paula Moreira, Antero Abrunhosa, Agneta Nordberg, Miguel Castelo‐Branco,

Advanced Neuroimaging Techniques and Applications

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.