Translation of novel imaging techniques into clinical use for patients with epilepsy

Lead Research Organisation: University College London
Department Name: Institute of Neurology

Abstract

Epilepsy is a common and serious neurological condition. A third of patients have seizures despite medication, which often arise from the temporal lobe. Surgical removal of this part of the brain can control the seizures in 60-70% but may result in impairments of memory, language, vision and mood.

I will use a novel MRI brain scanning technique to look at connections between the temporal lobe and other parts of the brain to determine the effects of epilepsy and neurosurgery on these areas of the brain. Through this I will show how MRI scans before surgery can predict whether a patient will suffer these adverse consequences, so patients can be better informed when making a decision on whether to have surgery.

For those deciding to have surgery, I will compare scans before surgery with those taken 3 and 12 months later to look at how the brain compensates. This information may additionally inform colleagues working in related fields such as brain injury. Finally, I will develop imaging techniques that can be used during surgery specifically to help the surgeon avoid damage to parts of the brain dealing with vision and so improve clinical outcome for the patient.

Technical Summary

Epilepsy affects over 450,000 people in the UK. One third continue to have seizures despite medication, carrying risks of premature mortality and physical, cognitive and psychosocial morbidity. Temporal lobe epilepsy (TLE) is the most common refractory focal epilepsy. Neurosurgical treatment controls seizures in 60-70% of patients but may adversely affect memory, language and visual fields.

The key research questions are:

1. What are the effects of TLE and anterior temporal lobe resection (ATLR) on the structural connectivity of the temporal lobe to neocortex, particularly language and memory pathways?
2. Can preoperative tractography predict possible adverse effects of ATLR on memory, language and visual fields, and therefore advise the surgeon in minimising these risks?
3. Can pre- and intra-operative tractography be combined with intra-operative neuronavigation to reduce the risk of damage to white matter tracts and thus improve the outcome of epilepsy surgery?

This project will clarify the effects of TLE and neurosurgery on white matter tracts, with prediction of risks and subsequent reduction in individual patients. Conventional MRI sequences do not adequately visualize white matter connections. Diffusion tensor imaging (DTI) is a non-invasive MRI technique which when analysed using tractography can visualize trajectories of white matter tracts.

Male and female subjects undergoing ATLR will have detailed evaluation prior to surgery and 3 and 12 months after surgery comprising MRI scans, including DTI, neuropsychological and neuropsychiatric tests. Control subjects will undergo the same assessment. Tractography will be performed using state-of-the-art Probabilistic Index of Connectivity (PICo) algorithms. Structural connectivity will be compared between the patient groups and control subjects and the changes in the year following surgery evaluated. The extent of connectivity will be correlated with the outcomes observed in memory, language and vision.

At present, up to 24% patients develop a visual field deficit that precludes driving following anterior temporal lobe resection (ATLR). Visualization of the optic radiation using tractography and integration of this information with neurosurgical navigation will reduce this risk and improve patient outcome. Techniques will be developed to combine tractography with the intra-operative neuronavigation system.

Current tractography techniques have limitations in data acquisition and processing. Several new developments to overcome these need implementation and critical evaluation. Serial tractography studies following acquired brain injury or before and after neurosurgery are also lacking. Tractography developments and serial studies that aid the understanding of structural reorganisation within white matter tracts will benefit patient care and inform colleagues in related fields, including acquired brain injury.

Publications

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Cardoso MJ (2012) Geodesic shape-based averaging. in Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention

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Kochan M (2015) Simulated field maps for susceptibility artefact correction in interventional MRI. in International journal of computer assisted radiology and surgery

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Modat M (2014) Global image registration using a symmetric block-matching approach. in Journal of medical imaging (Bellingham, Wash.)

 
Title Hipposeg 
Description Online algorithm for automated segmentation of hippocampi using large manual database 
Type Of Material Improvements to research infrastructure 
Year Produced 2012 
Provided To Others? Yes  
Impact Other epilepsy research groups investigating use of this free tool when they do not have local expertise 
URL https://hipposeg.cs.ucl.ac.uk
 
Description CMIC 
Organisation University College London
Department Centre for Medical Image Computing
Country United Kingdom 
Sector Academic/University 
PI Contribution All the data being used for this project is acquired by myself or colleagues. I am providing the clinical input into the development of the imaging methods and developing scripts and writing papers.
Collaborator Contribution Development and implementation of computational techniques for registered pre- and post-operative imaging data; to be used for implementation of tractography results in neuronavigational suite. Implementation of scripts for hippocampal segmentation and T2 mapping.
Impact Multiple papers (in publications), open access Hippocampal segmentation website (Hipposeg) and publicly available scripts for T2 mapping.
Start Year 2010
 
Description Newcastle Peter Taylor 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution Acquisition and supply and imaging data and clinical data and input into analysis and interpretation of results.
Collaborator Contribution Analysis of data, and supervision of a student in this area.
Impact Paper on impact of epilepsy surgery on structural connectome (Neuroimage Clinical 2018)
Start Year 2016
 
Description BBC1 Programme - How Science Changed Our World 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Research presented as part of a BBC1 television programme describing the top ten scientific breakthroughs in the past 50 years, one of which was the use of MRI scanning

Raised awareness of epilepsy and surgery
Year(s) Of Engagement Activity 2010
 
Description Epilepsy Research Centre opening 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Epilepsy Society Research Centre opening - gave poster presentation and laboratory tours to donors for the centre and to potential future donors


Additional funding pledged
Year(s) Of Engagement Activity 2013
 
Description Funders Visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presentation of my research results to a visit to the MRI Unit by those who have provided funding towards the unit, or other parts of the National Society for Epilepsy.

Funding continued.
Year(s) Of Engagement Activity 2010
 
Description NHNN 150th Anniversary 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Open day at the National Hospital for Neurology and Neurosurgery celebrating 150 years since its foundation. I presented the epilepsy section demonstrating the current epilepsy imaging research ongoing at the UCL Institute of Neurology to members of the public and also hospital staff. This included my research funded by the MRC.

Letter of thanks from Business Manager for hospital
Year(s) Of Engagement Activity 2010
 
Description Roundtable discussion about technologies, seizures and the public 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Workshop aiming to bring together a mixture of artists, scientists and the public to explore the artistic and medical representations of epilepsy. Arranged by Dr Julie Hartley as part of the EU funded HealthGovMatters project (http://www.healthgovmatters.eu/index.php?id=4)

Interesting debate between non-medical and medical with important queries raised
Year(s) Of Engagement Activity 2012