Title: A non-invasive intracranial pressure (nICP) monitoring system
Funder: Department of Health and Social Care

Abstract: The project will build on work already undertaken to develop a first version of the probe and instrumentation. On-going experiments using an in vitro cardiovascular circuit have provided proof of concept that pressure within a closed cavity can be estimated from optical signals from the tissue(9). The remainder of the current period of funding (until September 2016) will focus on collection of data under different physiological conditions in preparation for the commencement of the three-year project. Phase I: Development of hardware, calibration and in vitro evaluation The probe, which is designed for placement on the forehead above the eye, will be refined using experimental data and computer models of light interaction with tissue layers developed by the investigators. The current layout and specification of the optoelectronic components is based on our experience of sensors developed for past projects. Infrared radiation penetrates the skull and brain tissue and is partially absorbed by haemoglobin in the arterial blood, resulting in modulation of the backscattered optical signal by the principle of photoplethysmography (PPG). Multiple wavelengths will be used allowing selection of the detection depth to a region of optimum depth in the frontal lobe. An array of photodetectors will eliminate unwanted signals from extra-cerebral tissue (e.g. the scalp), while a reference signal is recorded from the scalp arteries to track changes in vascular tone and blood pressure. The pressure surrounding the cerebral arteries affect the characteristics and overall morphology of the recorded optical pulse waveform, so nICP may be calculated by analysing the differences between quantifiable features of the cerebral PPG signal and the scalp reference signal. These features are pulse arrival time, upstroke velocity, downstroke velocity/acceleration, pulse width and spectral components. The probe and instrumentation will be designed in consultation with patient and relatives focus groups and will meet all safety and medical device regulatory requirements. Once the probe design is finalised it will be manufactured using biocompatible materials and packaged ready for use by the manufacturing partner, Schurter Electronics Ltd. Phase II: Volunteer study and regulatory approval The system will be evaluated in healthy volunteers in the laboratories at City University to ensure reliability and reproducibility of reported nICP values. The aim of this study is to evaluate the functionality of the sensor and instrumentation and allow for the calibration for different head sizes, skull thicknesses etc. Service user involvement will be requested in aiding the design of the clinical investigations. A clinical trial protocol, patients and relatives information sheets and consent/assent forms will be developed with the full collaboration of service user groups. Research Ethics and MHRA applications will be made, requesting permission to perform measurements in 40 head-trauma and/or post-surgical patients. Phase III: Clinical Trial and Dissemination Following ethics approval, a pilot clinical trial will be conducted in the department of neurosurgery and trauma at the Royal London Hospital, the UK's largest major trauma centre. Forty head trauma and post-surgery patients indicated for invasive ICP monitors will be studied and nICP values will be compared with simultaneously recorded reference invasive ICP readings. Acquired data will be analysed and trends in the measured data will be correlated with clinical monitoring data and observations. Results will be disseminated in peer-reviewed journals, national and international conferences and at a service user discussion group. The project will deliver a prototype ready for full clinical validation. Throughout all phases of the project the corresponding technology transfer offices of both City University and Barts Health NHS Trust will engage in detailed market research analysis, securement of all IP, economic evaluation of the developed technology and actions to engage with potential manufacturing partners/licensees.

Lay abstract: Medical treatment received immediately after traumatic head injury is critical to the survival and recovery of the patient. Brain swelling often causes a rise in pressure within the rigid confines of the skull. This increase in so-called intracranial pressure can cause a reduction in blood supply to brain leading to irreversible injury or death in patients with severe head injuries. Standard pressure monitoring requires insertion of a sensor through a hole drilled into the skull by a neurosurgeon, a procedure that carries risks of life threatening bleeding and infection as well as delay in starting monitoring. The project aims to further develop a system for continuous non-invasive monitoring of intracranial pressure. A prototype is currently under development based on a probe that is placed on the forehead and illuminates the underlying brain tissue. Light sensors in the probe detect the light reflected back from the brain, which pulses as a result of the pulsation of the brain s blood vessels. Changes in the pressure surrounding the arteries affect the shape of the recorded pulse wave, so analysing the wave shape will allow calculation of the pressure within the skull, which will be displayed to the clinician in real time. The reported intracranial pressure will enable rapid assessment of newly admitted head injured patients to indicate the need for emergency procedures such as drainage of fluid from around the brain and allow doctors to plan long-term treatment. The proposed monitor could lead to significant improvements in survival rates, shortened hospital stays and reduced long-term disability. The technology could also benefit patients suffering from meningitis, hydrocephalus (water on the brain), liver failure and migraine. A final version of the system, designed for use in ambulances, emergency departments or intensive care units, will be developed and tested in healthy volunteers and hospital patients.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INJURIES AND ACCIDENTS