Novel noninvasive optical methods to characterise cerebral oxygen delivery and utilisation after traumatic brain injury

Head injury is a major cause of death and severe disability, affecting mainly young people. The injury itself causes immediate and irreversible damage and also initiates a cascade of changes that lead to continued brain damage (secondary injury) that can, in some circumstances, be prevented or treated. The degree of cell damage and death is related to reduction in brain oxygen supply and the inability of some brain cells to utilise oxygen effectively. Different regions of the brain will be affected to different degrees. Patients with severe head injury are monitored and treated on intensive care units where the aim is to minimise secondary brain injury.

Measurement of the pressure inside the head and the oxygen levels in the brain helps to guide the intensive care treatment of head injury. However, most established brain monitors have disadvantages; many are invasive and provide information about only a small part of the brain whereas others make ?average? measurements of the whole brain and miss important regional changes. Modern imaging techniques can provide sophisticated maps of the injured brain but such techniques are not generally available at the bedside and, in any case, only provide a ?snapshot? of information at one particular moment in time.

Near infrared spectroscopy (NIRS) is an inexpensive optical technique using low light levels to measure the distribution of oxygen and blood in the brain and crucially how oxygen is being utilised at a cellular level. The equipment is portable and well suited to measurements during neurointensive care. We have recently developed a novel NIRS system that specifically assesses cellular oxygen utilisation in the adult brain. The aim of this project is to use this new system to monitor brain oxygen levels in a large number of patients with head injury and to determine whether the brain cells are effectively utilising delivered oxygen. Because this system is non-invasive, measurements can be made at multiple sites in the brain, allowing a comparison of injured and uninjured areas. Continuous monitoring also allows minute-to-minute changes to be identified. This information will help doctors to decide which part of the brain is most affected by the injury and assist them in the delivery of targeted treatment.

The applicants have a strong history of public engagement in science activities including the Royal Society Science Exhibition (2006), radio and television programmes, lectures at the House of Commons and Royal Institution and numerous schools.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in the first four decades of life. Cerebral ischaemia and cellular hypoxia are central to the evolution of secondary brain injury and adversely affect outcome after TBI, although these pathophysiological processes are difficult to monitor continuously and non invasively during the intensive care management of head injury. The aim of this proposal is to use a novel, non invasive near infrared spectroscopy (NIRS) system to provide bedside measurements of oxygenation, haemodynamics and cellular oxygen metabolism continuously in brain injured patients. Specifically, a frequency domain multi distance spatially resolved broadband spectrometer will be used to monitor the redox state of cerebral oxidised cytochrome c oxidase (oxCCO), absolute tissue oxygen saturation and cerebral blood volume. This dual channelled system will allow measurements to be made simultaneously over injured and non-injured brain regions. We will perform a prospective, controlled, observational and interventional study in 70 patients with TBI over a two year period. We will monitor the above NIRS variables during standard protocol-guided treatment of TBI and during physiological perturbations. Patients will act as their own controls. NIRS signals will be correlated with measurements from a number of standard invasive intracranial monitors, including intracranial pressure, brain tissue oxygen tension, jugular venous oxygen saturation and tissue biochemistry (cerebral microdialysis), and with other non invasive measures including cerebral blood flow velocity (transcranial Doppler ultrasonography).
The data collected during these studies will allow us to characterise the time course of oxygenation, haemodynamic and metabolic changes in the injured brain continuously and non invasively for the first time. Characterisation of the changes in oxCCO might offer insights not only into the pathophysiology of brain injury but also into the effects of treatment interventions. Clinical data will also be incorporated into a mathematical model of cerebral autoregulation and mitochondrial energetics in order to aid the interpretation of the physiological basis of the NIRS oxCCO signal.

This project combines expertise in the intensive care management of head injury, medical physics, bioengineering and biochemistry and all of the investigators have a proven track record of interdisciplinary and translational research in this area. The results from this project may be used to guide neuroprotective strategies for brain injured patients and to inform the development of non invasive bedside monitors of the injured brain.