Head-to-head comparison among semi-quantification tools of brain FDG-PET to aid the diagnosis of prodromal Alzheimer's disease

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET. Aim: We aimed to head-to-head compare the diagnostic performance among three Statistical Parametric Mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's Disease (pAD) from controls. Methodology: Sixty-two pAD patients (MMSE score=27.0±1.6) and one hundred-nine healthy subjects (CTR)(MMSE score=29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included i) a cluster identified through the correlation analysis between [18]F-FDG-PET and a verbal memory test (VROI-1), ii) a VROI derived from the comparison between pAD and CTR (VROI-2), and iii) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). Results: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps and PALZ score whereas VROI-SVM performed significantly (p<0.005) better than any of the other methods. Conclusion: The study confirms the good accuracy of [18]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.