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

Petra Tomše; Eva Rebec; Andrej Studen; Matej Perovnik; Tomaž Rus; Luka Ležaić; Chris C Tang; David Eidelberg; Maja Trošt

doi:10.1016/j.ejmp.2022.04.016

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

Phys Med. 2022 Jun:98:131-138. doi: 10.1016/j.ejmp.2022.04.016. Epub 2022 May 7.

Authors

Petra Tomše¹, Eva Rebec², Andrej Studen³, Matej Perovnik⁴, Tomaž Rus⁵, Luka Ležaić⁶, Chris C Tang⁷, David Eidelberg⁷, Maja Trošt⁸

Affiliations

¹ Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia. Electronic address: petra.tomse@kclj.si.
² Faculty of Mathematics and Physics, University of Ljubljana, Jadranska ulica 19, 1000 Ljubljana, Slovenia.
³ Faculty of Mathematics and Physics, University of Ljubljana, Jadranska ulica 19, 1000 Ljubljana, Slovenia; Institut Jožef Stefan, Jamova cesta 39, 1000 Ljubljana, Slovenia.
⁴ Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
⁵ Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia.
⁶ Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia.
⁷ Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Dr, Manhasset, NY 11030, USA.
⁸ Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia; Department of Neurology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.

PMID: 35537328
DOI: 10.1016/j.ejmp.2022.04.016

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.

MeSH terms

Fluorodeoxyglucose F18
Humans
Multiple System Atrophy* / diagnostic imaging
Multiple System Atrophy* / metabolism
Parkinson Disease* / metabolism
Parkinsonian Disorders* / metabolism
Supranuclear Palsy, Progressive* / diagnostic imaging
Supranuclear Palsy, Progressive* / metabolism

Substances

Fluorodeoxyglucose F18