Glia Imaging Differentiates Multiple System Atrophy from Parkinson’s Disease: A Positron Emission Tomography Study with [11C]PBR28 and Machine Learning Analysis

Aurelija Jucaite, Zsolt Cselényi, William C. Kreisl, Eugenii A. Rabiner, Andrea Varrone, Richard E. Carson, Juha O. Rinne, Alicia Savage, Magnus Schou, Peter Johnström, Per Svenningsson, Olivier Rascol, Wassilios G. Meissner, Paolo Barone, Klaus Seppi, Horacio Kaufmann, Gregor K. Wenning, Werner Poewe, Lars Farde
Movement Disorders. 2021-10-05; 37(1): 119-129
DOI: 10.1002/mds.28814

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Jucaite A(1)(2), Cselényi Z(1)(2), Kreisl WC(3), Rabiner EA(4)(5), Varrone A(2),
Carson RE(6), Rinne JO(7), Savage A(8), Schou M(1)(2), Johnström P(1)(2),
Svenningsson P(9), Rascol O(10), Meissner WG(11)(12)(13), Barone P(14), Seppi
K(15), Kaufmann H(16), Wenning GK(17), Poewe W(17), Farde L(2).

Author information:
(1)PET Science Centre, Personalized Medicine and Biosamples, R&D, AstraZeneca,
Stockholm, Sweden.
(2)Department of Clinical Neuroscience, Centre for Psychiatry Research,
Karolinska Institutet, Stockholm, Sweden.
(3)Taub Institute, Department of Neurology, Columbia University Irving Medical
Centre, New York, New York, USA.
(4)Invicro, London, UK.
(5)Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, UK.
(6)Yale University PET Centre, New Haven, Connecticut, USA.
(7)Turku PET Centre, University of Turku and Turku University Hospital, Turku,
(8)R&D, AstraZeneca, Waltham, Massachusetts, USA.
(9)Section of Neurology, Department of Clinical Neuroscience, Karolinska
Institutet, Stockholm, Sweden.
(10)French MSA Reference Centre, Clinical Investigation Centre CIC1436,
Department of Neurosciences and Clinical Pharmacology, NeuroToul COEN Centre,
UMR 1 214-ToNIC and University Hospital of Toulouse, INSERM and University of
Toulouse 3, Toulouse, France.
(11)CRMR AMS, Service de Neurologie-Maladies Neurodégénératives, CHU Bordeaux,
Bordeaux, France.
(12)University Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
(13)Department of Medicine, University of Otago, Christchurch, New Zealand Brain
Research Institute, Christchurch, New Zealand.
(14)Neurodegenerative Disease Centre, University of Salerno, Salerno, Italy.
(15)Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
(16)Department of Medicine, NYU Grossman School of Medicine, New York, New York,
(17)Division of Clinical Neurobiology, Department of Neurology, Innsbruck
Medical University, Innsbruck, Austria.

BACKGROUND: The clinical diagnosis of multiple system atrophy (MSA) is
challenged by overlapping features with Parkinson’s disease (PD) and late-onset
ataxias. Additional biomarkers are needed to confirm MSA and to advance the
understanding of pathophysiology. Positron emission tomography (PET) imaging of
the translocator protein (TSPO), expressed by glia cells, has shown elevations
in MSA.
OBJECTIVE: In this multicenter PET study, we assess the performance of TSPO
imaging as a diagnostic marker for MSA.
METHODS: We analyzed [11 C]PBR28 binding to TSPO using imaging data of 66
patients with MSA and 24 patients with PD. Group comparisons were based on
regional analysis of parametric images. The diagnostic readout included visual
reading of PET images against clinical diagnosis and machine learning analyses.
Sensitivity, specificity, and receiver operating curves were used to
discriminate MSA from PD and cerebellar from parkinsonian variant MSA.
RESULTS: We observed a conspicuous pattern of elevated regional [11 C]PBR28
binding to TSPO in MSA as compared with PD, with « hotspots » in the lentiform
nucleus and cerebellar white matter. Visual reading discriminated MSA from PD
with 100% specificity and 83% sensitivity. The machine learning approach
improved sensitivity to 96%. We identified MSA subtype-specific TSPO binding
CONCLUSIONS: We found a pattern of significantly increased regional glial TSPO
binding in patients with MSA. Intriguingly, our data are in line with severe
neuroinflammation in MSA. Glia imaging may have potential to support clinical
MSA diagnosis and patient stratification in clinical trials on novel drug
therapies for an α-synucleinopathy that remains strikingly incurable. © 2021 The
Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of
International Parkinson and Movement Disorder Society.

© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on
behalf of International Parkinson and Movement Disorder Society.

DOI: 10.1002/mds.28814
PMID: 34609758 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus