Epilepsy.

Lead Research Organisation: MRC London Institute of Medical Sciences

Abstract

Epilepsy is very common: nearly 1 in 200 people have it. People with epilepsy suffer from seizures (fits) during which they will often lose consciousness, may shake uncontrollably and are at risk of hurting themselves. Treatment is with drugs which need to be taken regularly and long-term, often for years or for life. Drugs do not stop seizures in about one in three people with epilepsy. If drugs do not stop seizures, epilepsy surgery may be an option. For epilepsy surgery to be possible, the seizures must come from one part of the brain only. If this part of the brain deals with say movement or memory, it may not be possible to remove it. The part of the brain where seizures come from is usually identified through brain imaging (Magnetic Resonance Imaging, MRI; Positron Emission Tomography, PET) and by looking at electrical brain waves (Electro-Encephalo-Grams, EEGs). In our program, we use advanced brain imaging techniques in people with epilepsy and compare them with healthy people without epilepsy. Magnetic Resonance Imaging (MRI) is extremely useful in epilepsy, but is normal (i.e. does not explain why seizures occur) in about one in four people with uncontrolled seizures. The main brain imaging method we use is Positron Emission Tomography (PET). This is how it works: Nerve cells talk to each other using chemicals. These chemicals are released from one nerve cell and recognised by others around them. These chemicals fit to receptors on other nerve cells like a key fits in a lock. PET works by marking the key chemicals with tiny amounts of radioactivity. We then inject them into the person and use the PET camera to see where they go in the brain. From this information, we can work out how many of the locks there are in every part of the brain. PET may often show changes even when MRI is normal. We are also creating atlases which show the normal structure of the human brain better and better. We then use them to automatically label new brain scans, and also to automatically detect whether there is something wrong in people with epilepsy.

Technical Summary

Epilepsy is the most common serious neurological disorder, with 0.8% of the population affected. We are interested in alterations in brain structure, receptor architecture, and neurotransmission in the epilepsies. We use positron emission tomography (PET) with novel and established tracers to further our understanding of developmental and acquired changes in neurotransmitters and their receptors. Some of the main questions are: why seizures arise (e.g. through abnormal networks involving heterotopic neurons, or an imbalance of excitatory and inhibitory transmission), where they arise (using functional imaging techniques in conjunction with structural imaging (magnetic resonance imaging, MRI) to find focal abnormalities), and why they stop (using double scan paradigms to gather evidence for the release of a given neurotransmitter during seizures). The clinical relevance is twofold. Firstly, elucidating the role of certain neurotransmitter systems is helpful in working towards new antiepileptic drugs. Secondly, patients who fail to respond to antiepileptic drugs are usually considered for epilepsy surgery which aims to remove the epileptogenic part of the brain without damaging motor and intellectual function. PET and other techniques can help to pinpoint the abnormal area especially when MRI is normal. We are also interested in other aspects of epilepsy that are relevant for patients, for example searching for possible explanations for patients memory complaints which may be underpinned by changes in neurotransmission. During the PET work knowing where emerged as a major problem. This has spurred the development of a multi-subject probabilistic brain atlas; this technology has evolved into a research area in its own right that is actively pursued.

Publications

10 25 50
 
Title "PEbrain": explaining common epilepsy surgeries and the role of PET and MR imaging in preparing for surgery 
Description I obtained this grant together with some team members to create a life-sized 3D printed brain with removable parts to illustrate the role of imaging in the preparation for epilepsy surgery. Prototypes have been printed and look great. 
Type Of Art Artefact (including digital) 
Year Produced 2020 
Impact Not yet - will update once final product deployed. 
 
Description Action Medical Research, Project Grant
Amount £148,510 (GBP)
Funding ID AMR AP 1208 
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Dementias Platform UK MR-PET Partnership
Amount £860,793 (GBP)
Funding ID MR/N025792/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 03/2020
 
Description Dunhill Medical Trust Project Grant
Amount £173,262 (GBP)
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description King's College London Medical Engineering Centre of Research Excellence
Amount £12,100,395 (GBP)
Funding ID 203148/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 04/2022
 
Description Chiba 
Organisation National Institute of Radiological Science (NIRS)
Department Molecular Imaging Centre (NIRS)
Country Japan 
Sector Academic/University 
PI Contribution Provision of human brain atlases and know-how; intellectual input
Collaborator Contribution Creation of a novel method of partial volume effect correction; integration into other efforts to compare such methods
Impact New method for partial volume effect correction, now being implemented for other PET cameras. Publication: PMID: 18852055
Start Year 2007
 
Description DCEE IoN UCL 
Organisation University College London
Department Institute of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution Multiple research projects in collaboration
Collaborator Contribution Integration in patient care and epilepsy surgery programme, access to patients, help with patient recruitment, access to data, intellectual input
Impact PMID: 18809501 PMID: 17851093 PMID: 17764977 PMID: 17579659 PMID: 17428687 PMID: 17301080 PMID: 16671082
 
Description Imperial Imaging 
Organisation Imperial College London
Department Department of Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution Use of and further development of our manually constructed atlases, intellectual input, knowledge transfer, clinical / neurological angle on research, neuroanatomical knowledge, methods development, collaboration with students
Collaborator Contribution Knowledge transfer, computing infrastructure, intellectual input, collaborations with multiple studentsKnowledge transfer, computing infrastructure, intellectual input, collaborations with multiple students
Impact Tools for automatic anatomical segmentations of brain MRIs, disease classification tools, etc. Publications: PMID: 19815080 PMID: 19245840 PMID: 18979782 PMID: 18500985 PMID: 18051099 PMID: 18044611 PMID: 17428687 PMID: 17354848 PMID: 17354834 PMID: 16860573 PMID: 20079440 PMID: 20114079 PMID: 20114082 PMID: 20382238
 
Description Imperial Imaging 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Use of and further development of our manually constructed atlases, intellectual input, knowledge transfer, clinical / neurological angle on research, neuroanatomical knowledge, methods development, collaboration with students
Collaborator Contribution Knowledge transfer, computing infrastructure, intellectual input, collaborations with multiple studentsKnowledge transfer, computing infrastructure, intellectual input, collaborations with multiple students
Impact Tools for automatic anatomical segmentations of brain MRIs, disease classification tools, etc. Publications: PMID: 19815080 PMID: 19245840 PMID: 18979782 PMID: 18500985 PMID: 18051099 PMID: 18044611 PMID: 17428687 PMID: 17354848 PMID: 17354834 PMID: 16860573 PMID: 20079440 PMID: 20114079 PMID: 20114082 PMID: 20382238
 
Description PET Methodology 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Public 
PI Contribution Contribution of materials (data, human brain atlases), collaborations on improvements in data collection and corrections (e.g. motion correction, partial volume effect correction).
Collaborator Contribution Methodological and statistical input, intellectual input, important discussions to refine ideas and take them forward
Impact Multiple methodological improvements and new developments. PMID: 18852055 PMID: 18786637 PMID: 17851093 PMID: 17764977 PMID: 17579659 PMID: 17398120 PMID: 17204713 PMID: 16182554 PMID: 20870689
 
Title Atlas databases 
Description Atlas databases 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2006
Licensed Yes
Impact See other sections As of December 2011, over 100 academic licences have been granted; some atlas resources have been licenced to a company; a software company is in the process of taking a commercial licence. PS: As the atlas databases are automatically copyrighted, the question 8.4.1/8.4.2 makes no sense. The system forced me to give an answer so I put "2006" in.
 
Description 29. Professions in the community. Outreach event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Interactive 10-minute meetings with groups of pupils, Rudolf Steiner School Kings Langley, Hertfordshire, UK, 21st of November 2017 (1 hour, interaction with approx. 15 students)
Year(s) Of Engagement Activity 2017
 
Description 31. NIHR Cardiovascular Medtech and In vitro diagnostic Co-operative (MIC) Imaging Sciences Public and Patient Involvement (PPI) Panel: Presentation of planned and ongoing research projects & discussion with the panel (1.5h, about 10 patients and interested laypersons). London, UK, 18th of July, 2018 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact NIHR Cardiovascular Medtech and In vitro diagnostic Co-operative (MIC) Imaging Sciences Public and Patient Involvement (PPI) Panel: Presentation of planned & ongoing research projects & discussion with the panel (1.5h, about 10 patients and interested laypersons). London, UK, 18th of July, 2018
Year(s) Of Engagement Activity 2018
 
Description 33. Spare Parts: Parts to Spare. Panel discussion on brain surgery for Epilepsy as part of the "Spare Parts" season at Science Gallery London, UK, 30th of April, 2019 (approx. 100 participants). Initiated by me, and I was one of the discussants: https://london.sciencegallery.com/events/spare-parts-parts-spare 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Panel discussion on brain surgery for Epilepsy as part of the "Spare Parts" season at Science Gallery London, UK, 30th of April, 2019 (approx. 100 participants). Initiated by me, and I was one of the discussants.
We had a philosopher, two clinicians, a facilitator and a patient who had had (successful) brain surgery for epilepsy. While most of the audience were general public, there were many patients or patient group / charity representatives, too.
Year(s) Of Engagement Activity 2019
URL https://london.sciencegallery.com/events/spare-parts-parts-spare
 
Description Charing Cross Hospital, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact Where is the brain, and what does it do? Interactive presentation in a public space inside a hospital. Target: patients, staff

I don't think this was well pitched and don't think it had any impact.
Year(s) Of Engagement Activity 2007
 
Description Chinese student visit 20th of July 2017, led by Dr McGinnity, organised by Dr Ran Yan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Dr McGinnity gave a talk and a lab tour to 8 excellent pharmaceutical students from Hangzhou and Beijing universities in China
Year(s) Of Engagement Activity 2017
 
Description Cybertots Nursery, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Interactive presentation on the brain in a nursery (2-5 year olds)

The nursery teachers learned about, amongst other things, epilepsy which will be useful when they have children with epilepsy. For the toddlers, it is a bit early to say whether they will be more likely to study neuroscience as a result!
Year(s) Of Engagement Activity 2006
 
Description Interview by Dubai TV at New Scientist Live, 10 October 2019 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I was selected to give an interview to Dubai TV at New Scientist Live, 10 October 2019.
Episode covered in "The London Show", Dubai TV, available at https://vimeo.com/366639264/3103ba383b (coverage ~4min50 - 6min50)
Year(s) Of Engagement Activity 2019
URL https://vimeo.com/366639264/3103ba383b
 
Description Pint of Science intervention by Dr McGinnity: "Positrons and Protons; Picture this!" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Interactive 40-minute presentation as part of an evening during "Pint of Science" event "Inside-Out! Observing your insides, from the outside", 16 May 2017, Horse and Stables pub, London, UK. About 60 participants.
Year(s) Of Engagement Activity 2017
URL https://pintofscience.com/
 
Description Public Engagement Grant ""PEbrain": explaining common epilepsy surgeries and the role of PET and MR imaging in preparing for surgery" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Obtained Centre for Medical Engineering / King's College London grant
""PEbrain": explaining common epilepsy surgeries and the role of PET and MR imaging in preparing for surgery" to build a 3D brain model specifically for explaining and discussing epilepsy surgery. Awarded 18 Nov 2019.
This is for designing and building a life-sized 3D printed brain that can be partly taken apart to reveal imaging abnormalities. Prototype exists - once ready, this will be used to reach hundreds of people.
Year(s) Of Engagement Activity 2019
 
Description Public Engagement event - New Scientist Live. ExCel London, UK, 10 October 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact New Scientist Live is one of the biggest science shows in the country, and our School of Biomedical Engineering and Imaging sciences had one of the largest stands there (120m2 stand).
I was a whole-day volunteer at King's College London on 10 October and greeted about 2,500 visitors that day. We had well over 10,000 visitors in total, and many repeat visitors who reported that our stand was the best!
Year(s) Of Engagement Activity 2019
 
Description Science Museum, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Where is the brain? What does it do? How does it do that?. Interactive presentation for 8-9 year olds (several runs)

Hard to know. They liked it.
Year(s) Of Engagement Activity 2006
 
Description Tour of the PET Centre (Dr Colm McGinnity) as part of "Discover Chemistry at King's College London" 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Six groups of 5-6 students each visited
Year(s) Of Engagement Activity 2017
 
Description Two pints of brain, dissected during life. "Pint of Science" session by Alexander Hammers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Interactive 40-minute presentation as part of an evening during "Pint of Science" event "Inside-Out! Observing your insides, from the outside", 16 May 2017, Horse and Stables pub, London, UK. About 60 participants.
Year(s) Of Engagement Activity 2017
URL https://pintofscience.com/