Neurosurgical INTENSIVE CARE UNIT Research Group

Incorporating the Brain Monitoring Research Group

SUMMARY

Brain injury is a significant health burden because it causes death and severe disability, often in young people. Current techniques for monitoring the injured brain have disadvantages. We have developed and tested a comprehensive range of innovative, non-invasive optical monitors which measure regional changes in metabolic as well as oxygenation and haemodynamic variables as indicators of cerebral ischaemic damage following brain injury. In association with other components of the multi-modal array, these techniques offer the possibility to identify windows for targeted therapy after brain injury, thereby potentially reducing the risk of secondary brain damage. This might improve outcome in survivors and reduce the length of stay in neurointensive care, which is a costly and scarce resource in the UK.

The Neurosurgical Intensive Care Unit Research Group is a multidisciplinary group comprising neurointensivists, medical physicists, bioengineers and a mathematical modeller from the Departments of Neurosurgical Critical Care at the National Hospital for Neurology and Neurosurgery, UCLH and Medical Physics and Bioengineering, UCL.

RESEARCH TEAM

Head of department

Dr Martin Smith, Consultant and Honorary Professor in Neurocritical Care

Clinical Research Fellows

Dr Arnab Ghosh, Clinical Research Associate

Dr David Highton, Academic Clinical Fellow in Anaesthesia and Critical Care

Principle collaborator

Professor Clare Elwell, Department of Medical Physics and Bioengineering, UCL

Other collaborators

Dr Ilias Tachtsidis

Dr Murad Banjee

Dr Terence Leung

CURRENT PROJECTS

Investigation of cerebral oxygenation, haemodynamic and metabolic variables after brain injury

The Brain Monitoring Research Group continues to develop and test near infrared spectroscopic techniques for non-invasive bedside monitoring of cerebral oxygenation, haemodynamic and metabolic variables in real-time. We are:

· Measuring, for the first time in adults, changes in cerebral cytochrome c oxidase concentration (oxCCO) as part of a UKCRN portfolio registered study. oxCCO redox state reflects cellular energy status and may be a superior measure of cerebral oxygen delivery and utilization, and of impending ischaemia, than more conventional NIRS and other monitored variables.

· Developing and testing a novel hybrid optical spectrometer (HOS) that has been optimized to quantify sub-micromolar concentration changes of cerebral oxCCO in vivo. The HOS is a combination of a multi-distance frequency domain spectrometer, capable of decoupling scattering and absorption changes within tissue, in association with a multi-distance broadband spectrometer which provides an optimized spectral range and sensitivity and the ability to isolate oxCCO changes in the intracerebral layers of the adult head.

· Developing a mathematical model of cerebral physiology that has been used successfully to aid the interpretation of signals from multimodal monitors of systemic and cerebral physiology. Pilot data provide compelling evidence that measured data can be converted into relevant clinical information at the bedside.

Risk prediction models for traumatic brain injury

In association with colleagues from ICNARC and Cambridge, MS is one of the lead investigators of the UKCRN Portfolio registered Risk Adjustment in Neurocritical Care (RAIN) study. This prospective validation of risk prediction models for adult patients with acute traumatic brain injury is designed to evaluate the optimum location and comparative costs of neurocritical care in the NHS. The study began in 2009 and continues to recruit patients from many centres in the UK. In addition to being a lead investigator, MS is a member of the Study Steering Group.

TEACHING ACTIVITY

MD/PhD supervision

Postgraduate teaching

Royal College courses, intercalated BSc students,

Undergraduate teaching

Neuroanaesthesia & neurocritical care module, Anaesthesia final year SSM, Intercalated BSc students

SELECTED PUBLICATIONS

For a full list visit:

http://www.ucl.ac.uk/neuroscience/Page.php?ID=12&ResearcherID=511

The effect on cerebral tissue oxygenation index of changes in the concentrations of inspired oxygen and end-tidal carbon dioxide in healthy volunteers. Tisdall M, Taylor C, Tachtsidis I, Leung T, Elwell C, Smith M. Anesth Analg 2009; 109: 906-13

Relationship between brain tissue haemodynamics, oxygenation and metabolism in the healthy human adult brain during hyperoxia and hypercapnea. Tachtsidis I, Tisdall M, Leung T, Pritchard C, Cooper C, Smith M, Elwell C. Adv Exp Med Biol 2009; 645:315-20

Increase in cerebral aerobic metabolism by normobaric hyperoxia after traumatic brain injury. Tisdall M, Tachtsidis I, Leung T, Elwell, C, Smith M. J Neurosurg 2008; 109: 424-32

Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study. Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M. Acta Neurochir (Wien) 2008; 150: 461-70

Monitoring intracranial pressure in traumatic brain injury. Smith M. Anesth Analg 2008; 106: 240-248

Investigation of frontal cortex, motor cortex and systemic haemodynamic changes during anagram solving. Tachtsidis I, Leung T, Tisdall M, Devendra P. Smith M, Elwell C. Adv Exp Med Biol 2008; 614: 21-28

Perioperative uses of transcranial perfusion monitoring. Smith M. Neurosurg Clin N Am 2008; 19: 489-502

Changes in the attenuation of near infrared spectra by the healthy adult brain during hypoxaemia cannot be accounted for solely by changes in the concentrations of oxy- and deoxy-haemoglobin. Tisdall M, Tachtsidis I, Leung T, Elwell C, Smith M. Adv Exp Med Biol 2008; 614: 217-225

Multimodal monitoring in traumatic brain injury: current status and future directions. Tisdall M, Smith M. Br J Anaesth 2007; 99: 61-67

Near infrared spectroscopic quantification of changes in the concentration of oxidised cytochrome oxidase in the healthy human brain during hypoxaemia. Tisdall M, Tachtsidis I, Leung T, Elwell C, Smith M. J Biomed Opt 2007; 12: 024002/1-024002/7

Theoretical investigation of measuring cerebral blood flow in the adult human head using bolus indocyanine green injection and near-infrared spectroscopy. Leung T, Tachtsidis I, Tisdall M, Smith M, Delpy D, Elwell C. Appl Opt 2007; 46: 1604-14

Intensive care management of patients with subarachnoid haemorrhage. Smith M. Curr Opin Anaesthesiol 2007; 20: 400-407

Investigation of in-vivo measurement of cerebral cythochrome-c-oxidase redox changes using near-infrared spectroscopy in patients with orthostatic hypotension. Tachtsidis I, Tisdall M, Leung T, Cooper C, Delpy D, Smith M, Elwell C. Physiol Meas 2007; 28: 199-211

Early identification of secondary brain damage in subarachnoid haemorrhage: a role for glial fibrillary acidic protein. Petzold A, Keir G, Kerr M, Kay A, Kitchen N, Smith M, Thompson E. J Neurotrauma 2006; 23: 1179-1184

Cerebral microdialysis: research technique or clinical tool? Tisdall M, Smith M. Br J Anaesth 2006; 97: 18-25

Changes in cerebral oxygenation and haemodynamics during postural blood pressure changes in patients with autonomic failure. Hunt K, Tachtsidis I, Bleasdale-Barr K, Elwell C, Mathias C, Smith M. Physiol Meas 2006; 27: 777-785

Extracellular N-acetylaspartate depletion in traumatic brain injury. Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M, Tavazzi B, Vagnozzi R, Signoretti S, Amorini A, Bellia F, Lazzarino G. J Neurochem 2006; 96: 861-9

Axonal pathology in subarachnoid and intracerebral hemorrhage. Petzold A, Rejdak K, Belli A, Sen J, Keir G, Kitchen N, Smith M, Thompson EJ. J Neurotrauma 2005; 22: 407-14

Consensus meeting on microdialysis in neurointensive care. Bellander B, Cantais E, Enblad P, Hutchinson P, Nordstrom CH, Robertson C, Sahuquillo J, Smith M, Stocchetti N, Ungerstedt U, Unterberg A, Olsen N. Intensive Care Med 2004; 30: 2166-69

Measuring cerebral oxygenation during normobaric hyperoxia: a comparison of tissue microprobes, near-infrared spectroscopy, and jugular venous oximetry in head injury. McLeod AD, Igielman F, Elwell CE, Cope M, Smith M. Anesth Analg 2003; 97: 851-6

Role of serum S100B as an early predictor of high intracranial pressure and mortality in brain injury: a pilot study. Petzold A, Green AJ, Kier G, Fairley S, Kitchen N, Smith M, Thompson EJ. Crit Care Med 2002; 30: 2705-2710

SOURCES OF FUNDING

Medical Research Council

Wellcome Trust

UCL/UCLH Comprehensive Biomedical Centre

Central and East London CLRN

National Institute for Health Research

LINKS

http://www.ucl.ac.uk/neuroscience/Page.php?ID=12&ResearcherID=511

http://www.ucl.ac.uk/anaesthesia/

http://www.ucl.ac.uk/medphys/research/borl/

The UCL Institute of Neurology promotes teaching and research of the highest quality in neurology and the neurosciences. The Institute of Neurology and the National Hospital for Neurology and Neurosurgery are members of  UCL Partners, Europe's largest academic health science partnership.