MR Imaging of Brain Generators in Human Epilepsy

Lead Research Organisation: University College London
Department Name: UNLISTED

Abstract

New Brain Scans for Epilepsy. Epilepsy is the commonest serious neurological condition in the UK. Although medication can help, it is ineffective in 80,000 people. We propose to use a new kind of brain scan to find the brain area that is responsible for the seizures (epileptic focus) and that could be surgically removed.
The new brain scan technique, called EEG-fMRI, combines the recording of brain waves (electroencephalogram or EEG) with functional magnetic resonance imaging (fMRI). EEG-fMRI has already given promising results but we do not know how useful it is in localising the focus. We will first refine the technique to make it as sensitive and specific as possible and then evaluate its performance by comparing it with the best available data. We propose to develop EEG-fMRI on the most advanced scanners to maximise its sensitivity. We also want to compare the EEG-fMRI measurements with clinical data that is collected by placing electrodes inside the patient’s skull – a complicated and relatively risky procedure, but which, at present, gives the best possible localization of the epileptic focus. We hope to show that EEG-fMRI, a non-invasive and totally painless technique, can give the same kind of information as the invasive technique.

Technical Summary

Thirty percent of epilepsy patients are intractable to drug treatment, representing approximately one hundred thousand people in the UK. Many patients with intractable epilepsy are currently deemed unsuitable for curative surgery due to the difficulty in identifying the focus. Invasive monitoring is currently the gold standard but disadvantages of this approach include the risk of complication and costs. EEG-correlated fMRI (?EEG-fMRI?) is a non-invasive technique unique in its ability to provide activation maps of the hemodynamic (blood oxygen level-dependent or BOLD) correlates of specific epileptiform discharges. Despite limited sensitivity, concordance with non-invasive electroclinical findings on a lobar basis is frequent. Up to now, validation has relied on comparison with electroclinical findings, which is unsatisfactory as it does not allow to assess the technique?s true added clinical value. The demonstration that fMRI can enhance or even replace invasive monitoring would be a great advance and could significantly increase the proportion of patients in whom surgery is an option. This will require validation based on invasive EEG monitoring and postsurgical outcome findings in a representative group of patients.
Significant improvements in sensitivity will be obtained by implementing EEG-fMRI at high field (4.7T). Furthermore, we will investigate a novel fMRI contrast mechanism that directly reflects neuronal activity. To address scalp EEG?s intrinsic limitations, and in particular its low sensitivity and specificity, we will apply data-driven fMRI analysis techniques to reveal spatio-temporal patterns reflecting epileptogenicity. These developments will greatly benefit from the availability of invasive monitoring data.
fMRI activation patterns will be compared the epileptogenic substrate identified invasively. To further investigate the relationship between epileptogenicity and fMRI, discharges recorded within the brain and fMRI signals will be recorded simultaneously, requiring implementation of intracranial EEG-fMRI. In addition to the obvious interest in improving our understanding of the imaging correlates of epileptogenicity and epileptogenic networks, this presents us with a unique opportunity to improve multimodal forward models of EEG and fMRI and our understanding of fMRI in humans. Furthermore the role of EEG-fMRI in guiding invasive monitoring will be investigated.
This programme of research will result in a major improvement in the fMRI?s sensitivity to epileptiform activity, and provide vital information on EEG-fMRI?s clinical potential. It will also represent a major leap forward in our understanding of the relationship between neuronal activity and fMRI on the other.

Publications

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Blinowska K (2009) Multimodal imaging of human brain activity: rational, biophysical aspects and modes of integration. in Computational intelligence and neuroscience

 
Description Action Medical Research, Project Grant
Amount £200,000 (GBP)
Organisation Action Medical Research 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2009 
End 04/2012
 
Description Brain Research Trust Equipment Grant
Amount £40,550 (GBP)
Organisation Brain Research Trust (BRT) 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2009 
End 04/2011
 
Description NATIONAL INSTITUTE FOR HEALTH RESEARCH
Amount £77,077 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2013 
End 12/2016
 
Description PhD studentship
Amount £100,000 (GBP)
Organisation Government of Pakistan 
Sector Public
Country Pakistan
Start 09/2008 
End 09/2011
 
Title Dynamic Causal Modelling of Human EEG-fMRI Epilepsy Data 
Description These methods (developed within the Wellcome trust Centre for Neuroimaging) allow the inference of the initiators of a network of generators of brain activity that is form by a network of areas. 
Type Of Material Model of mechanisms or symptoms - human 
Provided To Others? No  
Impact By applying this method to generalised epilepsy cases EEG-fMRI data a new model of what was required for 'absence' seizures was infered. 
 
Title EEG-fMRI database in epilepsy patients 
Description The data was acquired in patients undergoing presurgical evaluation. All patients either had or will have epilepsy surgery. 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2008 
Provided To Others? Yes  
Impact Development of the methods and algorithms for localisation of epileptic foci and investigation of the dynamics of epileptic networks. 
 
Title ICA of FMRI 
Description We were the first to apply the data-driven analysis technique ICA to fMRI data of the resting state to detect epileptic patterns. 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact The publication of our work has resulted in publications from other investigators along similar lines. 
 
Title ICEEG-fMRI 
Description We have developed and implemented the technique of intra-cranial EEG-fMRI in humans and established the relevant safety parameters. 
Type Of Material Database/Collection of Data/Biological Samples 
Provided To Others? No  
Impact This is a world first, with no published articles describing this technique to date. We anticipate that the resulting data will revolutionise our understanding of the physiological substrate of spontaneous brain activity in particular epilepsy. 
 
Description Ad-Tech Medical 
Organisation Ad-Tech Medical Instrument
Country United States 
Sector Private 
PI Contribution This company has provided hardware in the form of products for us to test. In addition a partnership has been developing with funding applied for a collaborative partnership aimed at developing improved products.
Collaborator Contribution Provided free samples for testing.
Impact Grant nenewal application includes this industrial partnership
Start Year 2008
 
Description Christian Albrechts University Kiel 
Organisation University of Kiel
Department Neuropediatric Department Kiel
Country Germany 
Sector Academic/University 
PI Contribution We developed, implemented and applied a novel approach to analyse the EEG-fMRI data acquired in patients with frequent epileptic spikes aiming at direct detection of the neuronal currents in the fMRI data.
Collaborator Contribution Provided unique data which we analysed using our methodology
Impact A paper has been accepted for publication in an imprtant peer-reviewed journal.
Start Year 2007
 
Description Geneva 
Organisation University of Geneva
Department Epilepsy Unit
Country Switzerland 
Sector Academic/University 
PI Contribution We provided data, expertise in EEG-fMRI data fusion and manpower.
Collaborator Contribution Provided part-time clinical research fellow for a period of 18 months. and EEG analysis software and expertise.
Impact New methodology, greater insight into the generators of epileptic activity based on EEG-fMRI data. Three joint publications to date (PMID: 19408351, 19817805, 19948231 and one publication in press), with more in preparation.
Start Year 2007
 
Description Hammersmith Hospital 
Organisation Hammersmith Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We provided manpower to develop and run computer simulations.
Collaborator Contribution Expertise in modellng of electromagnetic and thermal effects on human body and implants related to MR
Impact Simulation results. No joint publication to date, but at least one planned.
 
Description Kings team 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution We acquired data from patients recruited by the collaborator and analysed it.
Collaborator Contribution Recruited patients for our study and provided data and clinical expertise.
Impact A significant amount of new data. Publications are under preparation with one currently in press.
Start Year 2006
 
Description Maastricht 
Organisation Maastricht University (UM)
Department Faculty of Psychology and Neuroscience
Country Netherlands 
Sector Academic/University 
PI Contribution We provided the data and manpower to run the analysis, with the help of our collaborators who supplied the methodology.
Collaborator Contribution Provided the projejct with new methodology to analyze our data and support, resulting in one publication to date and more being prepared.
Impact Entirely novel way of analysing our data. A joint publication in an important peer-reviewed journal resulted (PMID: 17889566).
Start Year 2006
 
Description Marseille team 
Organisation Aix-Marseille University
Department INSERM U751 (Stereotactic & Functional Neurosurgery)
Country France 
Sector Academic/University 
PI Contribution We acquired data on patiens recruited by the collaborator and analysed the data.
Collaborator Contribution Provided human subjects, data and expertise.
Impact Publicartions to date: PMID: 19408351, 19649252, 19948231, with two in press and many more in preparation.
 
Description Modena 
Organisation University of Modena and Reggio Emilia
Country Italy 
Sector Academic/University 
PI Contribution Data sharing and analysis
Collaborator Contribution Exchange of research staff.
Impact None yet.
Start Year 2010
 
Description North Bristol NHS Trust 
Organisation Frenchay Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We acquired data from the patients recruited by the collaborator and analysed and interpreted it, jointly with our collaborator.
Collaborator Contribution Recruited patients for our study and provided clinical data and expertise.
Impact EEG-fMRI data from 6 patients. One joint publication in press, with more in preparation.
Start Year 2007
 
Title EEG-fMRI 
Description Scalp EEG-fMRI for pre-surgical assessment of patients with drug-resistant epilepsy. 
Type Diagnostic Tool - Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2009
Development Status Under active development/distribution
Impact Funding as recently been obtained to conduct a hospital-based prospective study on the technique's efficacy at providing localisaing information in patients with drug-resistant epilepsy. The project started in May 2009. 
 
Description Review article in professional journal 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Article on "EEG, FMRI and Their Combination in the Study of Epilepsy" in Advances in Clinical Neuroscience & Rehabilitation journal.

None know to date.
Year(s) Of Engagement Activity 2008
 
Description Wikipedia article on EEG-fMRI 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact I wrote the article on EEG-fMRI in Wikipedia, and improved a number of articles in related areas.

The article has been edited by other people suggesting it is being consulted. We do not know whether data is available on the number of times an article is browsed.
Year(s) Of Engagement Activity 2006