Abnormal metabolic covariance patterns associated with multiple system atrophy and progressive supranuclear palsy

Abstract

Purpose: Differentiation between neurodegenerative parkinsonisms, whose early clinical presentation is similar, may be improved with metabolic brain imaging. In this study we applied a specific network analysis to 2-[¹⁸F]FDG PET brain scans to identify the characteristic metabolic patterns for multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in a new European cohort. We also developed a new tool to recognize and estimate patients' metabolic brain heterogeneity.

Methods: 20 MSA-P patients, 20 PSP patients and 20 healthy controls (HC) underwent 2-[¹⁸F]FDG PET brain imaging. The scaled subprofile model/principal component analysis was applied to identify MSA/PSP-related patterns; MSARP and PSPRP. Additional, 56 MSA, 45 PSP, 116 PD and 61 HC subjects were analyzed for validation. We innovatively applied heat-map analysis to extract and graphically display the pattern's regional sub-scores in individual subjects.

Results: MSARP was characterized by hypometabolism in cerebellum and putamen, and PSPRP by hypometabolism in medial prefrontal cortices, nucleus caudatus, frontal cortices and mesencephalon. Patterns' expression discriminated between MSA/PSP patients and HCs as well as between different parkinsonian cohorts (p < 0.001). Both patterns were sensitive and specific (AUC for MSARP/PSPRP: 0.96/0.99). Heat-map analysis showed differences within MSA/PSP subjects and HCs consistent with clinical presentation.

Conclusions: Replication and validation of MSARP and PSPRP confirms robustness of these metabolic biomarkers and supports its application in clinical and research practice. Heat-map analysis gives us an insight into the contribution of various pattern's regions to patterns' expression in individual subjects, which improves our insight into the heterogeneity of studied syndromes.

Keywords: Heat-map analysis; Metabolic brain pattern; Multiple system atrophy; Progressive supranuclear palsy.