INTRODUCTION: Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. METHODS: To promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies. RESULTS: As a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression). DISCUSSION: We suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials.

1st Department of Neurology Faculty of Medicine and CEITEC MU Masaryk University Brno Czech Republic

AXON Neuroscience CRM Services SE Bratislava Slovak Republic

Brain and Mind Centre Sydney Medical School University of Sydney Sydney NSW Australia

Center for Medical Education and Clinical Research Section of Neurology Buenos Aires Argentina

CNRS Institut des Sciences Cognitives Bron France

Danish Research Centre for Magnetic Resonance Copenhagen University Hospital Hvidovre Hvidovre Denmark

Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

Department of Clinical Neurosciences Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada

Department of Clinical Neurosciences University of Cambridge Cambridge United Kingdom

Department of Medical Surgery Neurological Metabolic and Aging Sciences University of Campania L Vanvitelli Caserta CE Italy

Department of Medicine Imperial College London London United Kingdom

Department of Neurology Clinica Universidad de Navarra Pamplona Spain

Department of Neurology Medical University of Innsbruck Innsbruck Austria

Department of Neurology UKSH Campus Kiel Christian Albrechts University Kiel Germany

Department of Neurology University of Michigan Ann Arbor MI USA

Department of Neurology University of Turku Turku Finland

Department of Neuroscience University of Padua Padua Italy

Department of Nuclear Medicine Inselspital Universitätsspital Bern Bern Switzerland

Department of Radiology Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada

Division of Clinical Neurology Department of Neurology Medical University of Innsbruck Innsbruck Austria

Division of Clinical Neurosciences Turku University Hospital Turku Finland

Division of Nuclear Medicine Department of Radiology University of Michigan and VAMC Ann Arbor MI USA

E J Safra Parkinson Disease Program Toronto Western Hospital and Krembil Research Institute UHN Toronto Ontario Canada

Forschungszentrum Jülich INM 2 Jülich Germany

German Centre for Neurodegenerative Diseases and Technical University Munich Department of Neurology Munich Germany

German Centre for Neurodegenerative Diseases Bonn Cologne Germany

hmCINAC University Hospital HM Puerta del Sur CEU San Pablo University Móstoles Madrid Spain

Hospices Civils de Lyon Hopital Neurologique Pierre Wertheimer Neurologie C Lyon France

Institut du Cerveau et de la Moelle épinière ICM Centre de NeuroImagerie de Recherche CENIR ICM Team Movement Investigations and Therapeutics Sorbonne Universités Inserm U1127 CNRS UMR Paris France

Mater Hospital South Brisbane QLD Australia

Multimodal Neuroimaging Department of Nuclear Medicine Medical Faculty and University Hospital University of Cologne Cologne Germany

National Institutes for Quantum and Radiological Science and Technology Chiba Japan

Newcastle Magnetic Resonance Centre and Positron Emission Tomography Centre Newcastle University Newcastle upon Tyne United Kingdom

Pacific Parkinson's Research Centre University of British Columbia Vancouver Canada

Queensland Brain Institute University of Queensland Brisbane QLD Australia

Research Imaging Centre Campbell Family Mental Health Research Institute CAMH Toronto Ontario Canada

Université de Lyon Université Claude Bernard Lyon 1 Faculté de Medecine Lyon Sud Charles Merieux Lyon France

University of Toronto Toronto Ontario Canada

VAMC Ann Arbor MI USA

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