Automatic covariance pattern analysis outperforms visual reading of ¹⁸F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) in variant progressive supranuclear palsy

Abstract Background To date, studies on positron emission tomography (PET) with 18 F‐fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP‐RS). Objectives To evaluate FDG‐PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. Methods This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non‐RS variants of PSP (vPSP), and 46 age‐matched healthy controls. Two state‐of‐the art methods for the interpretation of FDG‐PET were compared: visual analysis supported by voxel‐based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP‐related pattern. Results Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false‐negative cases was 10% in the PSP‐RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false‐negative cases was 0% in the PSP‐RS subsample and 15% in the vPSP subsample. Conclusions Visual interpretation of FDG‐PET supported by voxel‐based testing provides good accuracy for the detection of PSP‐RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP‐RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false‐positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel‐based testing of FDG‐PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.