Manchester Magnetic Resonance Neuroimaging Co-operative

Lead Research Organisation: University of Manchester
Department Name: Medical and Human Sciences

Abstract

Functional imaging is increasingly becoming an important tool in Neuroscience. It provides a way of identifying the regions in the human brain which are active during various tasks. The technique is safe, entirely non-invasive and can be applied equally to volunteers and clinical patients. In this group, there are researchers who are interested in how the brain processes chronic pain (particularly in arthritis), how eye-hand movements are co-ordinated, what brain regions may function differently in individuals in anti-social personality disorder, how inflammation plays a role in the development of brain damage following stroke, and how recovery of function after a stroke can be helped. Although the problems are diverse, the methods used to investigate them have much in common, using a core of similar techniques. By bringing the researchers together under the umbrella of a co-operative group, interchange of ideas will be facilitated and methods developed in one area of research will be available to the other groups to exploit in their own programmes. In addition, the co-operative will foster collaboration between research groups led by people in different disciplines, including basic scientists, physicians and psychiatrists.

Technical Summary

The aim of the co-operative group is to develop and implement improved methods for imaging-based research in order to underpin a range of projects utilising functional MR in the study of basic and clinical neuroscience, concentrating initially on pain, stroke, personality disorder and visuo-motor control. We are also requesting funds for a new component grant to investigate cortical plasticity. The proposed co-op will also provide a means to share technical support & scientific expertise amongst the members. Recent investment in imaging and new appointments by the University of Manchester and UMIST, together with support from the MRC and industry has resulted in a significant improvement in the facilities available for MR imaging. The proposed co-operative will have access to two new state-of-the-art scanners: a 1.5T Philips Intera sited in the Wellcome Trust Clinical Research Facility and a 3.0T Philips Intera-Achieva scanner (the first installation worldwide of this system) situated at Hope Hospital, Salford, where the University?s Clinical Neuroscience activity is based. Recognizing that multi-disciplinary working and good communication between user groups is the best way to exploit the benefits of the new scanners, we believe that a co-operative group will provide one important element in an overall strategy. In particular, the co-op will undertake development of core MR techniques to take advantage of the enhanced capabilities of the new scanners (high performance gradients - 60 mT/m on both scanners; parallel imaging, high field imaging) and make these available to all users of the systems. The remit of the co-op will go beyond the scientific and clinical objectives of the current components, and identify anatomical substrates and neurochemical mechanisms underlying plasticity, serious mental disorders, chronic pain, stroke pathogensis and motor programming. This work should in turn lead to clinical benefit through the development of appropriate therapies and of methods to evaluate them objectively. In collaboration with the Translational Imaging Unit, established by the University to manage the new imaging facilities, the co-op will aim to provide first class facilities for carrying out MR neuroimaging; support biological and clinical scientists to carry out MR studies, and to encourage a collaborative culture in which research topics and problems are openly discussed.

Publications

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Anderson IM (2008) Assessing human 5-HT function in vivo with pharmacoMRI. in Neuropharmacology

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Del-Ben CM (2005) The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an FMRI study. in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

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Elliott R (2010) Hedonic and informational functions of the human orbitofrontal cortex. in Cerebral cortex (New York, N.Y. : 1991)

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Kong Y (2010) Analysis of connectivity in the resting state of the default mode of brain function: a major role for the cerebellum? in International Journal of Modelling, Identification and Control

 
Description Biomedical catalyst fund
Amount £554,940 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 05/2013 
End 04/2015
 
Description Clinical Research Fellowship
Amount £240,492 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2008 
End 06/2019
 
Description FP6 Integrated Programme
Amount € 7,300,000 (EUR)
Organisation Sixth Framework Programme (FP6) 
Sector Public
Country European Union (EU)
Start 01/2004 
End 03/2010
 
Description Heptares Therapeutics Ltd
Amount £528,093 (GBP)
Organisation P1vital Consortium 
Sector Private
Country United Kingdom
Start  
End 03/2017
 
Description Lundbeck commercial/academic
Amount £237,068 (GBP)
Organisation P1vital Consortium 
Sector Private
Country United Kingdom
Start 06/2012 
End 12/2013
 
Description P1Vital; Sunovion Ltd
Amount £450,000 (GBP)
Organisation P1vital Consortium 
Sector Private
Country United Kingdom
Start 09/2014 
End 03/2016
 
Description Project resilience
Amount £517,529 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2009 
 
Description project opiate
Amount £300,000 (GBP)
Funding ID G1000018 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2009 
End 04/2011
 
Title connectivity analysis 
Description methods developed to cross-correlate brain activity in the default mode 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact Manuscript currently under preparation 
 
Title p-block pharmaco MRI analysis method 
Description Publications about a new way of visualising and quantifying neurotransmitter function by experimental drug challenge in MRI scanner 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2008 
Provided To Others? Yes  
Impact Other groups use it 
 
Description AZ chronic citalopram study 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution pharmacological-challenge fMRI study of the effects of an SSRI on regional brain activation. SSRI challenge was tested before and after treatment for 11d with therapeutic dose of SSRI or placebo
Collaborator Contribution Funded an original study to look at brain plasticity following SSRI treatment
Impact abstracts at imaging meetings. Internal company report, papers in preparation
Start Year 2006
 
Description AZ funded comparison ketamine vs AZD6765 phMRI 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution The coop facilitated the development of a novel method of imaging the direct effects of a drug on brain function, called the p-block method of pharmaco MRI. This a potentially important way of evaluating the actions of new compounds in development.
Collaborator Contribution Funding for MRI scans and RA salaries and investigator time
Impact 5 conference presentations and a poster prize. I Publication PMID: 27133029
Start Year 2010
 
Description AZ funded comparison ketamine vs AZD6765 phMRI 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution The coop facilitated the development of a novel method of imaging the direct effects of a drug on brain function, called the p-block method of pharmaco MRI. This a potentially important way of evaluating the actions of new compounds in development.
Collaborator Contribution Funding for MRI scans and RA salaries and investigator time
Impact 5 conference presentations and a poster prize. I Publication PMID: 27133029
Start Year 2010
 
Description Autifony 
Organisation Autifony Therapeutics
Country United Kingdom 
Sector Private 
PI Contribution Screening Autifony compounds in preclinical models of efficacy. Phase 1 evaluation of novel Autifony compound underway in heathy volunteers to demonstrate target engagement and efficacy. Does the drug antagonise the subjective and brain imaging effects of ketamine?
Collaborator Contribution Funding. Compounds. Scientific expertise
Impact No outcomes yet
Start Year 2013
 
Description BeneMin 
Organisation King's College London
Department Clinical Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We lead the BeneMin clinic trial of minocycline in early psychosis. EME/NIHR grant
Collaborator Contribution Recruitment of patients
Impact in pregress
Start Year 2011
 
Description BeneMin 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We lead the BeneMin clinic trial of minocycline in early psychosis. EME/NIHR grant
Collaborator Contribution Recruitment of patients
Impact in pregress
Start Year 2011
 
Description BeneMin 
Organisation Queen Elizabeth Hospital Birmingham
Country United Kingdom 
Sector Hospitals 
PI Contribution We lead the BeneMin clinic trial of minocycline in early psychosis. EME/NIHR grant
Collaborator Contribution Recruitment of patients
Impact in pregress
Start Year 2011
 
Description BeneMin 
Organisation University of Cambridge
Department Department of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution We lead the BeneMin clinic trial of minocycline in early psychosis. EME/NIHR grant
Collaborator Contribution Recruitment of patients
Impact in pregress
Start Year 2011
 
Description BeneMin 
Organisation University of Edinburgh
Department Division of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution We lead the BeneMin clinic trial of minocycline in early psychosis. EME/NIHR grant
Collaborator Contribution Recruitment of patients
Impact in pregress
Start Year 2011
 
Description MRC Spring study (MR/K020803/1) 
Organisation Cardiff University
Department Brain Research Imaging Centre (CUBRIC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Cubric: magneto ecncepahalography (MEG) & magnetic resonance spectroscopy (MRS) Nottingham: MEG and c13 MRS
Collaborator Contribution 3 centre collaboration to recruit patients with early and established psychosis for biomarkers of glutamate, GABA neurochemistry and function in early psychosis
Impact Just starting. See outpiuts of MR/K020803/1
Start Year 2013
 
Description MRC Spring study (MR/K020803/1) 
Organisation University of Nottingham
Department Sir Peter Mansfield Magnetic Resonance Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Cubric: magneto ecncepahalography (MEG) & magnetic resonance spectroscopy (MRS) Nottingham: MEG and c13 MRS
Collaborator Contribution 3 centre collaboration to recruit patients with early and established psychosis for biomarkers of glutamate, GABA neurochemistry and function in early psychosis
Impact Just starting. See outpiuts of MR/K020803/1
Start Year 2013
 
Description Manchester PET imaging aggression 
Organisation University of Manchester
Department Faculty of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution A PET imaging study has been carried out of the brain 5HT transporter andf 5HT2A receptor in impulsive aggressive individuals. Current analysis of genetic association with PET markers
Collaborator Contribution Recruited participants from MRC grant on antisocial personality disorder
Impact Pre- and postsynaptic serotonergic differences in males with extreme levels of impulsive aggression without callous unemotional traits: a positron emission tomography study using (11)C-DASB and (11)C-MDL100907. Rylands AJ, Hinz R, Jones M, Holmes SE, Feldmann M, Brown G, McMahon AW, Talbot PS. Biol Psychiatry. 2012 Dec 15;72(12):1004-11. doi: 10.1016/j.biopsych.2012.06.024. Epub 2012 Jul 25. PMID: 22835812
Start Year 2007
 
Description Servier 
Organisation Servier Laboratories
Country France 
Sector Private 
PI Contribution Pharmacological-challenge fMRI was used to image the effects of a novel anti-depressant on the brain
Collaborator Contribution Access to a new drug for testing
Impact Internal company report. Abstracts at neuroscience and imaging meetings. Papers under preparation
Start Year 2006
 
Description Sunovion 
Organisation Sunovion Pharmaceuticals, Inc.
Country United States 
Sector Private 
PI Contribution We recruit and test participants for their response to Sunovion's new drug that is a possible new and very novel antipsychotic
Collaborator Contribution Supply the compound fund 2 post-doc RAs
Impact None yet
Start Year 2013
 
Company Name p1vital 
Description www.p1vital.com Aims to develop biomarkers for CNS drug efficacy in early clinical development with academic departments and to use them in commercial studies with the pharmaceutical industry 
Impact several academic and commercial projects with results presented at major international meeting in europe and the USA
Website http://www.p1vital.com
 
Description All in the Mind, Radio 4 item on ketamine for depression  
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact About 20 emails volunteering for experiments and trials or wanting clinical help for resistant depression.
Year(s) Of Engagement Activity 2008
 
Description British Computer Society 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Lecture with long Q&A

material was well received so decided to use again for less specialist audience
Year(s) Of Engagement Activity 2008
 
Description Cafe Muse 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Media (as a channel to the public)
Results and Impact Lecture on fMRI
Talk on schizophrenia neurobiology
Talk on neurobiology of depression to 6th formers


Collaboration with an artist instigated.
Medical undergraduate in audience came to do a Project Option with me.
Very positive feedback from organisers and prolonged Q&A after Dalton talk
Year(s) Of Engagement Activity 2008,2012,2013
 
Description School visit 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Delivered lecture to a 6th form scientific society

recruited other speakers. Work experience
Year(s) Of Engagement Activity 2008
 
Description Work experience 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact hosted student for 2 weeks.

university course applied for in related area
Got into Nottingham Medical school
Year(s) Of Engagement Activity 2009