Random forest analysis of midbrain hypometabolism using [18F]-FDG PET identifies Parkinson's disease at the subject-level

Abstract

Parkinson's disease (PD) is currently diagnosed largely on the basis of expert judgement with neuroimaging serving only as a supportive tool. In a recent study, we identified a hypometabolic midbrain cluster, which includes parts of the substantia nigra, as the best differentiating metabolic feature for PD-patients based on group comparison of [18F]-fluorodeoxyglucose ([18F]-FDG) PET scans. Longitudinal analyses confirmed progressive metabolic changes in this region and, an independent study showed great potential of nigral metabolism for diagnostic workup of parkinsonian syndromes. In this study, we applied a machine learning approach to evaluate midbrain metabolism measured by [18F]-FDG PET as a diagnostic marker for PD. In total, 51 mid-stage PD-patients and 16 healthy control subjects underwent high-resolution [18F]-FDG PET. Normalized tracer update values of the midbrain cluster identified by between-group comparison were extracted voxel-wise from individuals' scans. Extracted uptake values were subjected to a random forest feature classification algorithm. An adapted leave-one-out cross validation approach was applied for testing robustness of the model for differentiating between patients and controls. Performance of the model across all runs was evaluated by calculating sensitivity, specificity and model accuracy for the validation data set and the percentage of correctly categorized subjects for test data sets. The random forest feature classification of voxel-based uptake values from the midbrain cluster identified patients in the validation data set with an average sensitivity of 0.91 (Min: 0.82, Max: 0.94). For all 67 runs, in which each of the individuals was treated once as test data set, the test data set was correctly categorized by our model. The applied feature importance extraction consistently identified a subset of voxels within the midbrain cluster with highest importance across all runs which spatially converged with the left substantia nigra. Our data suggest midbrain metabolism measured by [18F]-FDG PET as a promising diagnostic imaging tool for PD. Given its close relationship to PD pathophysiology and very high discriminatory accuracy, this approach could help to objectify PD diagnosis and enable more accurate classification in relation to clinical trials, which could also be applicable to patients with prodromal disease.