PET Methodology

Lead Research Organisation: MRC London Institute of Medical Sciences

Abstract

Positron emission tomography (PET) is a tomographic technique that, through a ring of detectors, measures the fate of natural molecules labelled with positron emitters (18F, 11C, 15O). The high-energy of the emitting radiation allows the injection of minimal quantities of these compounds so that the organ or process measured is not perturbed. PET measures allow the formation of quantitative images of rates of physiological processes in vivo. In contrast to structural imaging (CT, MRI), PET can be used to examine dynamic changes in selected functional processes, and its quantitative potential not only enables the localisation of functional changes but also the assessment of their magnitude. The use of PET is becoming common in research, clinical diagnostic and drug development. Transformation of regional tissue radioactivity measured by the PET scanner into the rate of a physiological process requires use of sophisticated designs, accurate calibrations and computational models to describe the radiation detection process as well as the kinetics of the radiotracer in the organ of interest. The groups focus is on the development of methodology for the quantitative estimation of physiological parameters from PET studies. Current research focuses on computational chemistry, neuro-informatics, image reconstruction, kinetic modelling and multimodal image integration.

Technical Summary

Background & Relevance|PET allows the formation of quantitative images of rates of physiological or biochemical processes in vivo. In contrast to structural imaging (CT, MRI), PET can be used to examine dynamic changes in selected functional processes, and its quantitative potential not only enables the localisation of functional changes but also the assessment of their magnitude. Currently in the UK there is an unprecedented investment in PET technology from academia and industry with two new major PET imaging centres recently opened (the GSK Clinical Imaging Centre at Hammersmith Hospital, London and the Wolfson Molecular Imaging Centre at the University of Manchester) and three more in planning (Bristol, Cardiff and Kings College in London). These will be recent additions to the already significant presence of PET technology in healthcare in the UK||Research Focus|The group focuses on the development of computational methodology (experimental design, mathematical/statistical modelling), theoretical and applied, for the quantitative estimation of physiological parameters from PET studies. Current research focuses on:||Computational Chemistry (Dr. Lula Rosso)|One of the most common reasons for a new PET radiotracer candidate failure is that high non-specific and sub cellular binding obscures the specific binding to the molecular target and, thus, reduces the quality of the PET scan data. With the advance of high speed computer and new algorithms, it is now possible to investigate important processes of biological systems at microscopic level over increasingly longer times. The goal is to reproduce in silico non-specific binding trends of in vivo PET experiments investigating the mechanisms and dynamics of lipid-radiotracer interaction. Eventually, this could provide a very useful screening tool to reduce potential ligands failure rate after in vivo PET evaluation.||Neuroinformatics (Dr. Subrata Bose)|The exquisite quantitative potential of PET makes this tomographic technique sensitive to the subtle changes in neuronal function that characterize psychiatric disorders. By combining the functional patterns detected by PET with ancillary data (family history, genetic profiling, proteomic and/or genomic data obtained from peripheral measures etc.) we aim to construct robust biomarkers of disease for diagnostic purposes. At the same time, PET can be used to validate peripheral biomarkers that can be used at a lower cost. Research focuses of the optimization of data-mining and multivariate statistical analysis techniques for application of pattern discovery in PET data.||Image Reconstruction/Corrections and Kinetic Modelling (Dr. Federico Turkheimer)|Transformation of regional tissue radioactivity measured by the PET scanner into the rate of a physiological or biochemical process requires use of sophisticated designs, accurate calibrations and computational models to describe the radiation detection process as well as the kinetics of the radiotracer in the organ of interest. The Unit is producing mathematical models and computational techniques of increasing complexity that account for the specific properties of scanners (geometry and sensitivity), the radiation emission process (scatter and random coincidences), the time activity of the tracer in relation to the physiology of the system (kinetic modelling), the nature of the organ imaged (multi-scale spatial modelling) and its anatomy (multimodal integration with CT and MRI images).

Publications

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Albrecht DS (2018) Pseudoreference Regions for Glial Imaging with C-PBR28: Investigation in 2 Clinical Cohorts. in Journal of nuclear medicine : official publication, Society of Nuclear Medicine

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Anderson AN (2008) Chromosomal profiles of gene expression in Huntington's disease. in Brain : a journal of neurology

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Angelis GI (2011) Convergence optimization of parametric MLEM reconstruction for estimation of Patlak plot parameters. in Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society

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Awad M (2007) A common system for the comprehension and production of narrative speech. in The Journal of neuroscience : the official journal of the Society for Neuroscience

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Ball G (2011) Executive functions and prefrontal cortex: a matter of persistence? in Frontiers in systems neuroscience

 
Title Neuroscience and Graphic Design 
Description This is a digital image library to improve peer-to-peer scientific graphical communication 
Type Of Art Artefact (including digital) 
Year Produced 2017 
Impact Linked to this initiative we organised a set of workshop to improve the creation of scientific and conceptual figures. A description of the event is reported here: https://neuroscience-graphicdesign.com/workshops/ 
URL https://neuroscience-graphicdesign.com
 
Description Book: Statistics without equations
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact New book published on Amazon devoted to the explanation of the basics tenets of statistics to the wider public (e.g. secondary school to postgraduate students, the general public).
URL https://www.amazon.co.uk/Statistics-without-equations-Federico-Turkheimer/dp/1530908213
 
Description ARSEP - Travel Grant Bursary
Amount € 5,000 (EUR)
Organisation ARSEP Foundation 
Start 03/2014 
End 03/2015
 
Description CRUK-EPSRC Imaging Centre (Co-PI)
Amount £12,600,000 (GBP)
Funding ID C2536/A10337 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2009 
End 09/2013
 
Description EC-FP7 InMIND
Amount £725,000 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 04/2011 
End 03/2016
 
Description EC-FP7-Decide (2.4m euros across 13 participants)
Amount £185,000 (GBP)
Funding ID RI 261593 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 09/2010 
End 08/2012
 
Description EPSRC Project Grant EP/E049451/1 Networks: Emergence and dynamics
Amount £345,549 (GBP)
Funding ID EP/E049451/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 09/2007 
End 08/2010
 
Description Glaxo Smithkline - Excellence in Imaging Centre
Amount £400,000 (GBP)
Organisation GlaxoSmithKline (GSK) 
Sector Private
Country Global
Start 07/2017 
End 08/2019
 
Description Innovative Medicine Initiative (IMI)
Amount € 8,838,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 11/2016 
End 10/2021
 
Description Myelin imaging in MS
Amount € 35,000 (EUR)
Organisation ARSEP Foundation 
Start 01/2017 
End 12/2018
 
Description Targeting neuroinflammation in schizophrenia
Amount £841,703 (GBP)
Funding ID MR/N027078/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description UK-Japan Travel Grant
Amount £12,000 (GBP)
Funding ID JP0871550 
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 01/2009 
End 12/2011
 
Description Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Dementia (NIMA).
Amount £5,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2017 
End 12/2018
 
Description CNR 
Organisation San Raffaele Hospital
Department Department of Biological and Technological Research (DIBIT)
Country Italy 
Sector Academic/University 
PI Contribution Contributed neural-net technology for the extraction of PET imaging biomarkers in schizophrenia
Collaborator Contribution Collaborative work on grid-based computational diagnostic
Impact EU-FP7 Grant, DECIDE
Start Year 2009
 
Description Center for Integrated Molecular Brain Imaging 
Organisation Lundbeck Foundation
Country Denmark 
Sector Charity/Non Profit 
PI Contribution Development of network-based approaches for brain PET data analysis
Collaborator Contribution Access to PET database and scientific advisory
Impact BrainPET 2017 conference proceeding
Start Year 2016
 
Description IMANOVA 
Organisation Imanova
Country United Kingdom 
Sector Private 
PI Contribution Jointly set-up computational platform for PET data-analysis.
Collaborator Contribution Joint methodological work on clinical studies on Positron Emission Tomography
Impact Collaboration just started. A series of grant applications are expected
Start Year 2011
 
Description Imperial College London 
Organisation Imanova
Country United Kingdom 
Sector Private 
PI Contribution Methodology development and quantification for imaging neuroinflammation in HTLV-1 patients Quantification of the specific binding of the second generation TSPO tracers using blocking agents
Collaborator Contribution Imperial college initialised the study initialisation. Study was operated by Imanova
Impact This work has been presented in SNMMI annual meeting 2013
Start Year 2013
 
Description NIRS Chiba - Japan 
Organisation National Institute of Radiological Science (NIRS)
Department Molecular Imaging Centre (NIRS)
Country Japan 
Sector Public 
PI Contribution Collaborative Research PET Methodology
Collaborator Contribution Collaborative Research Papers
Impact Royal Society Travel Grant 2 collaborative publications
Start Year 2009
 
Description University of Padova 
Organisation University of Padova
Department Department of Information Engineering
Country Italy 
Sector Academic/University 
PI Contribution PhD student supervision
Collaborator Contribution Time for staff and students to projects
Impact Joint papers, software packages
Start Year 2006
 
Title CLICKFIT 
Description Software toolbox for the kinetic analysis of regional PET data. 
Type Of Technology Software 
Open Source License? Yes  
Impact This is the historical software of the Cyclotron Unit that has been subsided by the newer toolboxes 
 
Title Chromowave 
Description Software for the analysis of microarray expression data modelling chromosomal expression 
Type Of Technology Software 
Year Produced 2008 
Impact Software has been released and requested from ~20 Research Groups around the world 
 
Title P-PLOT 
Description Statistical Computational toolbox for the Multiple Comparisons problem. 
Type Of Technology Software 
Year Produced 2006 
Open Source License? Yes  
Impact We stopped recording the downloads in 2003 when it had reached 200. The method is widely used both in industry and in academia around the world. 
 
Title Phiwave 
Description Matlab toolbox for the analysis of PET images using wavelets 
Type Of Technology Software 
Year Produced 2006 
Open Source License? Yes  
Impact Opensource code that has been incorporated in other packages 
 
Title Piwave 
Description Tool for kinetic modelling of PET data using wavelets 
Type Of Technology Software 
Year Produced 2006 
Open Source License? Yes  
Impact Software was open source and has been integrated in many packages 
 
Title SUPERPK 
Description Software for the quantification of [11C]-(R)-PK11195 PET studies 
Type Of Technology Software 
Year Produced 2007 
Impact The software is now the basic analysis tool for PET studies in neuroinflammation. It is the standard for the European INMiND Consortium that gathers all EU PET centres doing neuroinflammation imaging 
URL http://www.uni-muenster.de/InMind/
 
Description 1st International Training School on PET-MRI Engineering 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact PhD students across entire Europe working in Neuroimaging field

New acquisition modalities and image analysis approaches are now tested in multiple research centers
New collaborations across institutes
Year(s) Of Engagement Activity 2014
URL http://www.pet-mri.eu/PETMR_School_14.html
 
Description KCL Molecular Neuroimaging YouTube Channel 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We have created a YouTube channel where we have installed a series of introductory lectures as well as short pieces presenting to the interested public our research work
Year(s) Of Engagement Activity 2017,2018
URL https://www.youtube.com/channel/UCCu_TK13NmIU8LXIFj_XU7A
 
Description PET Methodology Course 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The PET MEthodology course is a 3 days course attended by academics, NHS staff and professionals from Industry (GE, Phillips) and Pharma (GSK, Novartis, Roche) from the whole of the UK and from abroad.

The course has been running since 2008 with more than 500 participants and is regularly overbooked
Year(s) Of Engagement Activity 2008,2009,2010,2011,2012
URL https://www.kcl.ac.uk/prospectus/images/uploads/accreditions/PET_course_PROGRAM_March2014.pdf
 
Description TSPO Workshop Manchester 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Consensus meeting on imaging neuro-inflammation with PET

The meeting lead to the successful strategic grant application to the Wellcome
Year(s) Of Engagement Activity 2014