Fast optical tomography for imaging seizure activity in newborn infants

Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng

Abstract

We are proposing to develop a new way of imaging seizures in the brains of newborn babies, by shining light harmlessly across the head. This project is motivated by our recent discovery, using optical techniques, of previously unknown fluctuations in blood volume in the brains of babies diagnosed with seizures. Every year in the UK, over 1000 babies born at term are diagnosed with seizures, and the condition is even more common in infants born prematurely. Seizures usually cause convulsive body movements, and are due to abnormal electrical activity in the brain. This activity can usually be measured using a method known as electroencephalography (EEG). However EEG has significant limitations: it cannot detect activity occurring deep inside the brain and was normal during the unusual blood volume fluctuations we observed optically. Accurate diagnosis is important because seizures are not just a symptom of a medical problem, but are themselves a potential cause of brain injury. The work we propose will lead to better diagnosis and understanding of infant seizures, and underpin research into better treatments.

We plan to modify an existing optical imaging system to acquire data simultaneously with EEG measurements, and develop new schemes which enable images to be acquired much faster and with fewer data than is currently possible. This is essential in order to study the fluctuations observed previously, and determine how they evolve over time within different parts of the brain. The research will involve developing a new theoretical analysis, and designing new ways of processing the recorded data to extract the required information. We will also explore a novel way of combining optical and electrical measurements together to provide simultaneous three-dimensional maps of electrical activity and blood volume changes. All the new techniques will be tested on tissue-simulating phantoms before conducting a programme of studies on newborn babies with a high risk of seizures. We also propose to organise a Workshop, inviting other scientists and doctors interested in combining different medical imaging techniques to examine brain activity, in adults as well as children.

Planned Impact

The major beneficiaries from the proposed research, beyond academia, are as follows:
a) The primary beneficiaries of this project are newborn infants for whom seizures are disabilitating and represent a potential cause of brain injury. We aim to establish that optical imaging should be combined with EEG to give a more informed assessment of the seizing infant brain, and thus underpin research into better therapies. The prevention of lifelong disability resulting from brain injury represents a massive benefit to society as well as to the quality of life of the individuals concerned. Early identification of infants at risk is essential in minimising the impact of brain injury; every infant with improved neurological outcome will translate into substantial reductions in costs to both the NHS and wider social care services. The timescale for impact on research into new therapies is likely be within 5-10 years, although the timescale for the direct impact on infants is uncertain as it depends on outcomes of subsequent clinical trials (which our work will impact through the availability of suitable technology).
b) The technology and methodology developed for this project are likely to impact other patient groups for whom three-dimensional optical imaging of haemodynamic activity in the brain could lead to greater understanding of a clinical condition and therefore ultimately to improved treatments. One of the most promising of these additional clinical applications is the diagnosis and assessment of adult seizures. Fast optical tomography of the adult brain will be restricted to imaging the outer (cortical) regions, but otherwise the technology is completely transferrable to adults. Furthermore, if we successfully establish a link between optical signals obtained non-invasively and cortical spreading depolarisation (CSD), this could have very major implications to the study and treatment of migraine, which is considered to be associated with CSD-type phenomena.
c) Medical technology industries and the wider UK economy would benefit from establishing optical imaging as a clinically effective adjunct modality to EEG for the diagnosis and assessment of seizures. We propose to demonstrate a fast optical tomography instrument which is entirely compatible with commercial EEG systems (i.e. as an "add-on" device). A successful outcome to our project should create a commercial market for the new technology, and ensure that the UK takes a lead in development of the emerging industry. The timescale for such impact is likely to be fairly immediate (within 1-2 years) after the completion of the project.

Publications


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Dempsey L (2017) Geometrically complex 3D-printed phantoms for diffuse optical imaging in Biomedical Optics Express
Singh H (2016) Neurovascular Interactions in the Neurologically Compromised Neonatal Brain. in Advances in experimental medicine and biology
 
Description 1. For the first time, four-wavelength time-domain diffuse optical tomography has been performed on tissue-simulating media with a temporal resolution of less than 30 seconds.
2. Full-scalp diffuse optical imaging of the infant brain has discovered large pathological fluctuations in blood volume during seizures confirmed using simultaneous EEG.
3. Blood volume changes during seizures correlate closely with electrographic signals.
Exploitation Route Discovery of previously unknown blood volume changes needs to be confirmed in a larger cohort of infants, and longitudinal studies should be performed to see how their incidence correlates with clinical outcome.
Sectors Healthcare