According to the Brain Trauma Foundation Guidelines (4th Edition, 2016), ‘it is not monitoring per se that affects outcomes; rather, it is using the information from monitoring to direct treatment. Treatment informed by data from monitoring may result in better outcomes than treatment informed solely by data from clinical assessment. These recommendations are related to the influence on patient outcomes of three types of monitoring: ICP, cerebral perfusion pressure monitoring and advanced cerebral monitoring (eg intracerebral microdialysis). Clinical practice in most high-income countries incorporates multiple monitoring approaches as well as ongoing clinical assessment. As such, treatment decisions are not made using one source of information in isolation. Conversely, limited resources in low-and- middle- income countries often do not allow for technology-based monitoring, and medical decisions may be driven by clinical assessment alone.’ There is considerable scope for innovative technology in the field of brain injury which will enhance current clinical investigation and treatment and develop novel approaches in both adults and in children in both high and low/middle income countries.
Aims and specific short (1 year), medium (2-3 years) and long (4-5 years) objectives
Short (1 year):
- Find: Revisit unmet needs with patient and carers and other sectors (sports, industry, etc.). In addition to stakeholder workshops, run BITT tank to establish gaps to inform year 2-3.
Medium (2-3 years)
- Faciliate: Focus pilot competition in areas identified in year 1, and follow projects and build further collaborations.
Long (4-5 years)
- Foster: Work with wider-innovation landscape to leverage further funding
SUBTHEME 1: Clinical application of multimodality monitoring in intensive care
Brain oxygen and microdialysis monitoring technology have been established in clinical practice to assist in the management of patients on an intention to treat basis. This has been facilitated by two major consensus conferences (Neuro Critical Care Consensus meeting; Philadelphia; Menon, Hutchinson, Czosnyka and the International Microdialysis Forum held in Cambridge; Hutchinson, Carpenter, Helmy, Menon). Experience in monitoring over 500 patients in Cambridge, with intracranial pressure, brain tissue oxygen and microdialysis monitoring (lactate/pyruvate ratio; glucose), has provided the data to define treatment targets based on derangements in oxygenation and metabolism. Current treatment is directed by an algorithm based on intracranial pressure.
Multimodality monitoring in children with acute brain injury
The Technicam cranial access device with combined intracranial pressure, brain tissue oxygenation and brain chemistry monitoring pioneered in adults has been applied to paediatric traumatic brain injury. Preliminary results show a relationship between monitored parameters and outcome and the data is being used to define treatment thresholds (Young 2016 J Neurosurg Pediatr Res).
Refining clinical protocols
We will develop protocols for both traumatic brain injury and subarachnoid haemorrhage with refinements in the ICM+ technology to capture and display all data parameters. This approach will be applied to both adults and children to address the challenge of different pathophysiology (e.g. increased tendency to hyperaemia in paedatric traumatic brain injury) and to address age-related thresholds.
SUBTHEME 2: Increasing the understanding of the pathophysiology of acute brain injury
Novel substrates (13C chemistry) are being applied to map metabolic pathways and potentiate impaired cerebral metabolism. These include the use of 13C glucose to map glycolysis and the pentose phosphate pathway and 13C succinate to potentiate the action of the tricarboxylic acid (TCA) cycle. 13C studies to date have focused on administration as microdialysis substrate to dose a focal volume of brain.
We propose extending this concept to intravenous administration to monitor the whole brain in conjunction with MRI. This will require the production of new iv 13C substrate (glucose and acetate) and enable the measurement of TCA cycle activity and ATP production (31P MRS).
SUBTHEME 3: Novel monitoring technology
Refining microdialysis technology
Multimodality monitoring utilising catheters is by its nature focal and hitherto the exact volume of monitored brain remains unclear. We plan to add gadolinium to the microdialysis substrate followed by MRI in to determine the extent of diffusion and flow characteristics of microdialysis monitoring.
We are developing a new chemistry sensor to enable cerebral metabolism to be monitored continuously (collaboration with Professor Stephen Elliot and Dr Tanya Hutter, Department of Chemistry). The benefits objective is too streamline the analysis (dispense with manual vial changes) increase the time resolution and reduce costs. Initial funding from the NIHR brain injury HTC enabling pilot work has led onto successful grants from MRC confidence in concepts and NIHR i4i programs.
Novel external sensors
Current monitoring requires the insertion of three separate probes into the brain. Concurrent with the clinical trials of our new brain chemistry sensor we will explore the feasibility of combining intracranial pressure and focal oxygenation and metabolism monitoring into one cerebral catheter. A further advance is the application of wireless technology to reduce the current requirement for wires between patient and monitor, which impedes both nursing care and transfer from intensive care to radiology and theatre.
SUBTHEME 4: Development of 3D cranioplasty printing and novel internal sensors (SmartSkull: Sensor-Integrated Smart Wireless Skull-Monitoring System)
There is increasing interest in the application of decompressive craniectomy for the management of brain swelling due to trauma and other causes. Subsequent cranioplasty is now commonly undertaken with a synthetic material such as titanium. We have pioneered the development and application of 3D printing of titanium plates for skull reconstruction (cranioplasty) following decompressive craniectomy and other indications for bone flap removal. This has been successfully applied to nine patients and provides a platform for the development of a SMART cranioplasty device. Following cranioplasty, the patient is at risk of complications including raised intracranial pressure and seizures. This applies particularly to patients at risk of hydrocephalus. Currently, patients are assessed post-operatively by clinical observation, which is not sufficient.
We propose the development of new technology to integrate wireless sensors on a titanium implant to provide the ability to measure intracranial pressure and brain electrical activity. The sensors’ output will provide objective monitoring and enable treatment to be applied before patients deteriorate. We are proposing to incorporate sensors on the inner surface of the titanium cranioplasty plate – the’ SmartSkull’.
SUBTHEME 5: Addressing the challenge of assessing outcome
Fundamental to the assessment of the impact of monitoring and treatment is the determination of clinical outcome in the middle and longer term. Achieving six month follow up and beyond is a challenge in patients with acute brain injury. Currently methods include postal questionnaires, telephone follow up and clinic visit, all of which have disadvantages. We therefore propose to develop on line outcome assessments including the development of an app to improve the rate and quality of outcome data collection.
SUBTHEME 6: Developing technology for low and middle incomecountries
There is increasing recognition of the importance of head injury as a cause of death in low and middle income countries. This is particularly in relation to road traffic collisions. There are considerable gains to be made along the whole pathway of management. In addition to prevention, these include improving pre-hospital care (education of bystanders in first aid, provision of ambulances), emergency hospital care (access to emergency department resuscitation, access to CT), acute hospital care (access to neurosurgery and intensive care; provision of monitoring), on-going hospital care (in-patient rehabilitation) and community rehabilitation. We propose a number of cost-effective strategies to address each component of the pathway. These include the acute detection of haematomas using mobile technology (near- infrared scanning) in those with delayed access to CT and the development of non-invasive monitoring of ICP. Various methods are proposed and will be further explored in terms of feasibility and accuracy They include optic nerve sheath diameter (ONSD) measurement by ultrasound, tympanic membrane displacement measurement and intraocular pressure measurement.
Follow-up is a particular challenge in low and middle income countries with difficultly establishing postal addresses. The increasing application of SMART telephones is particularly attractive in these countries. We will exploit this in a number of ways including the development of an app tailored to these countries for follow up and using SMART phone displays as the monitor for portable US probes to measure optic nerve sheath diameter.
SUBTHEME 7: Monitoring mild traumatic brain injury and concussion
The recognition of concussion and mild traumatic brain injury is becoming of increasing importance, including sport-related concussion / mild traumatic brain injury. There are challenges in terms of establishing the diagnosis and decision making particularly in terms of return to activity including sport. Current approaches rely on clinical judgement supplemented by testing e.g. SCAT-3. There is a void in terms of monitoring technology, although several promising techniques are currently being investigated. These include the application of sensor arrays built into helmets, transcranial magnetic stimulation, Doppler ultrasound to detect brain pulsations and vestibulo-ocular motor screening. Research funded by the HTC, led by University of Stirling, has identified small but significant changes in brain function immediately after routine football heading practice (Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading, Wilson et al, 2016 EBioMedicine). We propose to evaluate the technology that is currently available and explore new methods to determine the nature of mild brain injury in terms of initial diagnosis, progress of symptoms and treatment.