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

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.

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.