Decomposed FDG PET-based phenotypic heterogeneity predicting clinical prognosis and decision-making in temporal lobe epilepsy patients

Objective This study utilized a data-driven Bayesian model to automatically identify distinct latent disease factors represented by overlapping glucose metabolism patterns from F-18-Fluorodeoxyglucose PET (F-18-FDG PET) to analyze heterogeneity among patients with TLE. Methods We employed unsupervised machine learning to estimate latent disease factors from F-18-FDG PET scans, representing whole-brain glucose metabolism patterns in seventy patients with TLE. We estimated the extent to which multiple distinct factors were expressed within each participant and analyzed their relevance to epilepsy burden, including seizure onset, duration, and frequency. Additionally, we established a predictive model for clinical prognosis and decision-making. Results We identified three latent disease factors: hypometabolism in the unilateral temporal lobe and hippocampus (factor 1), hypometabolism in bilateral prefrontal lobes (factor 2), and hypometabolism in bilateral temporal lobes (factor 3), variably co-expressed within each patient. Factor 3 demonstrated the strongest negative correlation with the age of onset and duration (r = - 0.33, - 0.38 respectively, P < 0.05). The supervised classifier, trained on latent disease factors for predicting patient-specific antiepileptic drug (AED) responses, achieved an area under the curve (AUC) of 0.655. For post-surgical seizure outcomes, the AUC was 0.857, and for clinical decision-making, it was 0.965. Conclusions Decomposing F-18-FDG PET-based phenotypic heterogeneity facilitates individual-level predictions relevant to disease monitoring and personalized therapeutic strategies.