Wearable neuroimaging technologies for the neonatal intensive care unit: mapping sensorimotor disruption in infants at risk of cerebral palsy.

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

Abstract

Newborn infants are extremely vulnerable to brain injury. The cause and nature of newborn brain injuries varies widely, but one common factor is that infants who suffer a brain injury at birth often go on to develop cerebral palsy.

Cerebral palsy is a group of permanent movement disorders that can severely limit the control of the muscles, and can have a devastating impact on quality of life. Cerebral palsy is the most common form of childhood disability in Europe and every year, approximately 1800 children in the UK are diagnosed with the condition. Cerebral palsy also has a significant impact on families and on society. It is estimated that the costs of care and support for people with cerebral palsy exceeds £1.4 Billion per year in the UK.

The early diagnosis of cerebral palsy is critical. While there is no cure for the condition, there are a number of treatments that can improve an infant's long-term motor ability. During the first few weeks and months of life the brain is highly adaptable, which means it is likely to be at its most susceptible to treatment. If infants with abnormal motor development could be identified early, these treatments would have the greatest chance of success. At present, the majority of infants with cerebral palsy are not diagnosed until 1 or 2 years-of-age. By this point it is likely too late for treatment to have the best possible impact. In 2015, the government held an inquiry into issues surrounding cerebral palsy in the UK and highlighted the urgent need for more research to support the early and objective diagnosis of the condition.

In healthy children and adults, the parts of the brain that control movement and receive somatosensory input (such as touch sensation) are organized like a map of the body. It has been shown that this organization is disrupted in children and adults with cerebral palsy. If we could monitor this disruption in the infant at the cot-side, it would be possible to provide an early and objective identification of infants who are developing abnormally. At present, there is no technology that can provide the precision, resolution, patient comfort or motion tolerance necessary to achieve this.

The aim of this fellowship is to address these challenges and develop a new wearable functional brain imaging technology that will allow infant somatosensory and motor organization to be mapped at the cot-side. I will use flexible electronics to construct a miniaturized imaging array that will incorporate hundreds of emitters and detectors of near-infrared light to safely monitor infant brain function. This imaging array will be fixed into a soft, elastic head-cap that can be worn comfortably by a newborn baby. By designing and integrating an advanced form of motion tracking, and by developing novel signal processing approaches, I will maximize the precision and motion tolerance of this imaging technology to allow brain function to be mapped during touch stimulation and during natural movement. I will then validate this system using carefully controlled laboratory experiments and a comprehensive functional imaging study in healthy adults. Finally, I will translate this technology to the neonatal clinic and investigate the development of somatosensory and motor function in both healthy and brain-injured infants from preterm through to 6 months-of-age. In doing so, I aim to demonstrate a new approach to the objective identification and monitoring of infants with cerebral palsy.

Planned Impact

The most significant impact of this fellowship will be on infants at risk of developing cerebral palsy (CP). CP is the most common form of childhood disability in Europe and causes a lifelong, debilitating loss of motor control and co-ordination that has a significant impact on quality of life. At present, approximately 1800 infants are diagnosed with CP each year in the UK, and this figure is not decreasing. While there is no cure for CP, there are a number of proven therapeutic approaches that can mitigate its impact. There exists a critical period of neuroplasticity in the first weeks and months of life, and the early identification of infants with sensorimotor abnormalities is essential to optimizing their motor outcome. Furthermore, because the condition evolves in a complex manner over the perinatal period, it is essential to be able to monitor high-risk infants over time. By producing a new generation of wearable DOT technologies that can be used to track the development of infant sensorimotor functional organization, I will demonstrate that it is possible to objectively identify and monitor motor abnormalities across the perinatal period. Cost-effective, longitudinal monitoring will make it possible to target clinical resources where they can have the greatest benefit. It will be possible to instigate individualized physiotherapeutic intervention earlier than ever before, which will maximize the treatment's potential to mitigate the effects of brain injury. By investigating post-injury neurodevelopment and by providing the means to monitor the effect of treatment on the sensorimotor cortex, this research programme will also impact the development and assessment of future interventional strategies.

In addition to infants at risk of CP, this fellowship has the potential to affect the diagnosis, management and treatment of a broad range of neurological conditions. This research programme will stimulate the development of a new generation of wearable neuromonitoring technologies that will have wide-reaching clinical implications. Accurate, real-time, continuous bed-side imaging of cerebral haemodynamics will be possible for the first time. This will have a significant and long-lasting impact on conditions including epilepsy, hypoxic ischaemic injury, traumatic brain injury and stroke.

The innovations of this research programme will also have a significant commercial and economic impact. The IP generated by this fellowship, and the licensing, production and sales of the associated technology will yield substantial economic benefit to the UK. By dramatically broadening the range of possible applications, the technological advances described in this fellowship will immediately accelerate the growth of the optical neuroimaging research market. The research stimulated by this fellowship will ultimately result in a new generation of clinical devices that will also have significant commercial potential. The clinical market will include maternity hospitals, physiotherapy and neurorehabilitation centres, intensive care units and neurology hospitals. By exploiting existing links with Hitachi Ltd., Hamamatsu Photonics K. K. and project partner Gowerlabs Ltd., I intend to ensure the rapid commercialization and translation of this technology. This fellowship therefore has the potential to stimulate the creation of a new UK-based medical device industry.

Publications

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Bunketorp Käll L (2018) Adaptive motor cortex plasticity following grip reconstruction in individuals with tetraplegia. in Restorative neurology and neuroscience

 
Description In the first phase of this fellowship, I developed a prototype adult wearable neuroimaging technology that was used to produce the first ever 3D functional images of the human brain using a wearable device (Chitnis et al., 2016). We then undertook a review of the progress of the field in this area (Zhao et al., 2017). and collected data for a second paper using this wearable technology, a paper which is currently in review. Since then, we have been adapting this technology for infant applications. Several prototypes of the infant system have now been constructed, and tested in infants ranging from the newborn to 7 months of age has been performed. My PhD student has just completed a 20-subject trial of one of these prototypes for imaging the brain in 6-month-old infants, and we are preparing the paper for submission. This will be the first study to ever yield 3D images of infant brain function in this context. We have also piloted recordings using one of our wearable devices in the hospital environment for the first time, and expect to begin extensive clinical recordings in the next few months.

I have also used this fellowship to build a sizeable, and successful research group. Known as DOT-HUB (www.ucl.ac.uk/DOT-HUB), the group now consists of 2 post-docs and 4 PhD students working on a range of applications and developments of my fellowship technology. I am also working closely with Gowerlabs Ltd. (www.gowerlabs.co.uk) to commercialize these technologies - a process that has resulted in the production of a commercial device which is now for sale and generating revenue for the UK.
Exploitation Route In addition to the commercialization of this technology described above (www.gowerlabs.co.uk/LUMO), we have already seen several other groups produce work that is directly inspired by our own (e.g. Wyser et al., Neurophotonics, 4(4), 041413 (2017); von Lühmann et al., OSA BIOMED 2020 (https://www.researchgate.net/publication/338709993_Towards_Neuroscience_in_the_Everyday_World_Progress_in_wearable_fNIRS_instrumentation_and_applications)).
Sectors Education,Electronics,Healthcare,Manufacturing, including Industrial Biotechology

URL http://www.ucl.ac.uk/dot-hub
 
Description In collaboration with our industrial parter, Gowerlabs Ltd. , this technology has already have commercial impact - namely in the creation of the device 'LUMO' for the research market (www.gowerlabs.co.uk/LUMO). This commercialization success is approximately 2 years ahead of the schedule set out in my Pathways to Impact, and has resulted in a number of sales and the generation of hundreds of thousands of pounds for the UK economy.
First Year Of Impact 2019
Sector Electronics,Healthcare
Impact Types Economic

 
Description Collaboration with Basque Center for Brain and Language (BCBL, Spain) 
Organisation Basque Center on Cognition, Brain and Language
Country Spain 
Sector Academic/University 
PI Contribution In establishing a collaboration with BCBL, I hosted a visiting PhD student at UCL for 6 months and provided extensive training and support.
Collaborator Contribution This researcher (Borja Blanco) was present in my group at UCL for 6 months and contributed directly to my project research goals.
Impact Sleep State Modulates Resting-State Functional Connectivity in Neonates, Front Neurosci - Brain Imaging Methods - in press.
Start Year 2019
 
Description Collaboration with Centre for the Developing Brain 
Organisation St Thomas' Hospital
Department Centre for the Developing Brain
Country United Kingdom 
Sector Hospitals 
PI Contribution One of the PhD student's in my team (Liam Collins-Jones) has been working full time with the CDB to process elements of the brain imaging data from the developing human connectome project in order to make it suitable for application as part of my research project.
Collaborator Contribution Dr. Tom Arichi has supervised Liam at CDB, and has contributed a significant amount of time to support the project.
Impact Abstract submitted and poster presented/to be presented at: SFNIRS, 2018, Tokyo Japan OHBM, 2019, Rome, Italy, BioMedEnd 2019, London, UK
Start Year 2018
 
Description Royal Institute Family Fun Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact My research group (DOT-HUB) led a research engagement stall at the Royal Institute Family Fun Day in October of 2019. This was a full day of discussing science (particularly optics) with members of the public - both children and adults.
Year(s) Of Engagement Activity 2019
URL https://www.rigb.org/whats-on/events-2019/october/public-family-fun-day-chaos-contagions-and-cur