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Alzheimers Dement (Amst). 2019 Apr 2;11:301-309. doi: 10.1016/j.dadm.2019.01.011. eCollection 2019 Dec.

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System.

Author information

1
Multimodal Neuroimaging, Department of Nuclear Medicine, Medical Faculty and University Hospital, University of Cologne, Cologne, Germany.
2
German Centre for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany.
3
Department of Neuroscience, University of Padua, Padua, Italy.
4
Department of Neurology, UKSH, Campus Kiel, Christian-Albrechts-University, Kiel, Germany.
5
Division of Nuclear Medicine, Department of Radiology, University of Michigan, and VAMC, Ann Arbor, MI, USA.
6
Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
7
VAMC, Ann Arbor, MI, USA.
8
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
9
Forschungszentrum Jülich, INM-2, Jülich, Germany.
10
German Centre for Neurodegenerative Diseases (DZNE), and Technical University Munich, Department of Neurology, Munich, Germany.
11
National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
12
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.
13
Brain & Mind Centre, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
14
Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
15
Department of Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
16
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
17
Mater Hospital, South Brisbane, QLD, Australia.
18
AXON Neuroscience CRM Services SE, Bratislava, Slovak Republic.
19
Newcastle Magnetic Resonance Centre & Positron Emission Tomography Centre, Newcastle University, Newcastle upon Tyne, United Kingdom.
20
Center for Medical Education and Clinical Research, Section of Neurology, Buenos Aires, Argentina.
21
Department of Medicine, Imperial College London, London, United Kingdom.
22
hmCINAC, University Hospital HM Puerta del Sur, CEU-San Pablo University, Móstoles, Madrid, Spain.
23
First Department of Neurology - Faculty of Medicine and CEITEC MU, Masaryk University, Brno, Czech Republic.
24
Department of Neurology, Clinica Universidad de Navarra, Pamplona, Spain.
25
Department of Nuclear Medicine, Inselspital, Universitätsspital Bern, Bern, Switzerland.
26
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
27
Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, Canada.
28
Department of Medical, Surgery, Neurological, Metabolic and Aging Sciences, University of Campania, "L. Vanvitelli", Caserta CE, Italy.
29
Université de Lyon, Université Claude Bernard Lyon 1, Faculté de Medecine Lyon Sud Charles Merieux, Lyon, France.
30
Hospices Civils de Lyon, Hopital Neurologique Pierre Wertheimer, Neurologie C, Lyon, France.
31
CNRS, Institut des Sciences Cognitives, Bron, France.
32
Department of Neurology, University of Turku, Turku, Finland.
33
Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
34
Division of Clinical Neurology, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
35
Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
36
E.J. Safra Parkinson Disease Program, Toronto Western Hospital & Krembil Research Institute, UHN, Toronto, Ontario, Canada.
37
Research Imaging Centre, Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada.
38
University of Toronto, Toronto, Ontario, Canada.
39
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

Abstract

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.

KEYWORDS:

Biomarker; CBD; CBS; Harmonization; MRI; MSA; Multicentric; Multisite; Neurodegeneration; Neuroimaging; PET; PSP; Trials

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