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Abstract

Objective:

Activated microglia are thought to play a major role in cortical gray matter (GM) demyelination in multiple sclerosis (MS). Our objective was to evaluate microglial activation in cortical GM of patients with MS in vivo and to explore its relationship to measures of disability.

Methods:

Using PET and optimized modeling and segmentation procedures, we investigated cortical 11C-PK11195 (PK11195) binding in patients with relapsing-remitting MS (RRMS), patients with secondary progressive MS (SPMS), and healthy controls. Disability was assessed with the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale (MSIS-29).

Results:

Patients with MS showed increased cortical GM PK11195 binding relative to controls, which was multifocal and highest in the postcentral, middle frontal, anterior orbital, fusiform, and parahippocampal gyri. Patients with SPMS also showed additional increases in precentral, superior parietal, lingual and anterior superior, medial and inferior temporal gyri. Total cortical GM PK11195 binding correlated with EDSS scores, with a stronger correlation for the subgroup of patients with SPMS. In patients with SPMS, PK11195 binding also correlated with MSIS-29 scores. No correlation with disability measures was seen for PK11195 binding in white matter. Higher EDSS scores correlated with higher levels of GM PK11195 binding in the postcentral gyrus for patients with RRMS and in precentral gyrus for those with SPMS.

Conclusions:

Microglial activation in cortical GM of patients with MS can be assessed in vivo. The distribution is not uniform and shows a relationship to clinical disability. We speculate that the increased PK11195 binding corresponds to enhanced microglial activation described in postmortem SPMS cortical GM.

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Supplementary Material

File (supplemental_data.doc)
File (znl03012000496.pdf)

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Information & Authors

Information

Published In

Neurology®
Volume 79Number 6August 7, 2012
Pages: 523-530
PubMed: 22764258

Publication History

Received: May 31, 2011
Accepted: December 29, 2011
Published online: July 3, 2012
Published in print: August 7, 2012

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Disclosure

M. Politis has served in the advisory board and received consultancy fees from Abbott and receives research support from Michael J. Fox Foundation for Parkinson's Research. P. Giannetti receives research support from European federation of neurologic societies. P. Su reports no disclosures. F. Turkheimer receives research support from the PET Methodology program grant from the Medical Research Council. S. Keihaninejad and K. Wu report no disclosures. A. Waldman has received consultancy fees from Bayer Schering. O. Malik has served in the advisory board and received consultancy fees from Biogen/IDEC Plc and Merck-Serono. P. Matthews is a full-time employee of GlaxoSmithKline Ltd and has served in the advisory board and received honoraria from Medical Research Council. Additionally, he serves as an editorial board member for Nature Reviews Neurology, holds stocks and options in GlaxoSmithKline Ltd, receives book royalties from Oxford University Press and MIT Press, and receives research training support from the Medical Research Council, Wellcome Trust, and EU FP7 Marie Curie Programme. R. Reynolds has received consultancy fees from Eisai London Plc and receives research support from the Medical Research Council. R. Nicholas has received consultancy fees and honoraria from Merck Serono, Novartis, and TEVA. P. Piccini has received research support from the Michael J. Fox Foundation for Parkinson's Research, Parkinson's UK, EU FP7, and CHDI. SUPERPK is licensed by Imperial Innovations, Ltd, but licenses are available for academic investigators at no cost. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

Marios Politis, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
Scientific board for Abbott
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paolo Giannetti, MD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Scientific Fellowship in 2009 (one year) from the European Federation of Neorological Societies (EFNS)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paul Su, MSc
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Federico Turkheimer, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
2010 – 2014, DECIDE, The European Commission, 7th Framework Programme; 2010 – 2014, Medical Research Council, Project Grant no. G0900891; 2009 – 2011, The Royal Society; 2008 – 2013CRUK-EPSRC Imaging Centre; 2007 – 2010EPSRC; 2006 – 2012, Core funding–PET Methodology, Grant no. U1200.04.004.000001.01, MRC
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Shiva Keihaninejad, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kit Wu, MRCP
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Adam Waldman, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Bayer Schering, speaker honoraria
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Clinical MR Neuroimaging; Physiological and Functional Techniques, Cambridge University Press, 2004 (1st ed), 2009 (2nd ed).
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
GlaxoSmithKline; general consultancy on imaging.
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Omar Malik, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paul M. Matthews, DPhil
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
PMM is an employee of GlaxoSmithKline Research and Development, Ltd and holds stocks and options. He has received remuneration for attendence at MRC COEN, TRG, and Board meetings. He has received attendence fees from HEFCE as part of the REF process. He has received speaking honoraria from UCSF, Consort MS Societies and with Wiener Wissenschafter Foundation.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Editorial board of Nature Rev Neurology
Patents:
1.
NONE
Publishing Royalties:
1.
FMRI: a primer, OUP, 2001; The memory process, MIT press, 2010; The bard on the brain, Dana Press, 2003
Employment, Commercial Entity:
1.
PMM is an employee of GlaxoSmithKline Research and Development, Ltd
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
GSK
Research Support, Government Entities:
1.
MRC, EU Marie Curie
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
Stock and options, GSK
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
GSK, 2005-
Legal Proceedings:
1.
NONE
Richard Reynolds, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Neuroscience Research, Editorial Advisory Board Member, 2010/11.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Medical Research Council, G0700356, PI, 2007-2010,
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
MS Society, UK MS Tissue Bank, PI, 1998-2014.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Richard Nicholas, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
Biogen; Merck Serono; Novartis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Biogen; Teva; Novartis
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
UK Medical Research Council
Research Support, Academic Entities:
1.
Wellcome; UK Multiple Sclerosis Society
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Paola Piccini, PhD
From the Centre for Neuroscience (M.P., P.G., P.S., F.T., K.W., A.W., P.M.M., R.R., R.N., P.P.), Division of Experimental Medicine, Faculty of Medicine, Hammersmith Hospital, Imperial College London, London; Clinical Sciences Center, Medical Research Council (M.P., P.G., P.S., F.T., S.K., K.W., A.W., P.P.), and GSK Clinical Imaging Centre (P.M.M.), Hammersmith Hospital, London; Dementia Research Centre (S.K.), UCL Institute of Neurology, London; and Department of Clinical Neurosciences (O.M., R.N.), Imperial College Healthcare NHS Trust, London, UK.
Disclosure
Scientific Advisory Boards:
1.
1) Parkinson’s UK Association of British Neurologist (ABN) Movement disorders section
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Parkinson’s UK (UK) Michael J Fox Foundation (USA) CHDI (USA) European Community FP7
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Study funding: Supported by grants from the Medical Research Council, UK (Clinical Sciences Center, Neurology group and PET Methodology group core grants, period 2008–2010; G0700356 to R.R.). F.T. acknowledges support from the MRC postgraduate training grant (G0900891). A.D. and R.N. acknowledge support from the Biomedical Research Centre.
Correspondence & reprint requests to Dr. Politis: [email protected]

Author Contributions

Study concept and design: Marios Politis, Richard Reynolds, Richard Nicholas, Paola Piccini. Drafting the manuscript: Marios Politis. Revising the manuscript: All authors. Acquisition of data: Marios Politis, Paolo Giannetti, Kit Wu. Analysis of data: Marios Politis, Paul Su, Federico Turkheimer, Shiva Keihaninejad. Interpretation of data: Marios Politis, Adam Waldman, Omar Malik, Paul M. Matthews, Richard Reynolds, Richard Nicholas, Paola Piccini. Statistical analysis: Marios Politis.

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