A data-driven SSM/PCA analysis approach for differential diagnosis of parkinsonism using 11C-PE2I PET

Journal article, 2026

Background Scaled Subprofile Modelling using principal component analysis (SSM/PCA) is a multivariate analysis technique primarily used in ¹⁸F-FDG PET brain studies to produce disease-specific patterns (DPs) and scalar scores aiding neurological diagnosis. SSM/PCA relies on well-characterized reference groups, posing challenges in real-world clinical datasets where diagnoses may be uncertain. A data-driven ensemble approach may offer a more robust alternative to random sampling when reference groups are unavailable. Objective To apply SSM/PCA to dynamic ¹¹C-PE2I-PET data for differential diagnosis of parkinsonism using a Monte Carlo cross-validation-inspired framework with ensemble prediction. Methods Dopamine transporter availability, expressed as the specific binding ratio (SBR) relative to cerebellar gray matter and relative cerebral blood flow (R1) images from 47 healthy controls and 316 patients who underwent dynamic¹¹C-PE2I-PET on a Discovery MI PET/CT scanner were included. Patients had a single most probable diagnosis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), or progressive supranuclear palsy (PSP) based on clinical information and the PET reading. A stratified 80/20 training/testing split was applied, repeated across 100 seeds, to generate DPs used for training ensemble classification models. Classification accuracy was assessed on the test-set. Results Combining SBR and R1 improved accuracy yielding a balanced accuracy of 90%, with SBR primarily differentiating patients from healthy controls and R1 for differentiating between PD, DLB and PSP. Conclusions Our results highlight the potential of an ensemble-based SSM/PCA method to assist differential diagnosis of parkinsonism. Future work will focus on including additional atypical parkinsonian disorders.