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

Lead Research Organisation: University College London
Department Name: Medical Physics and Biomedical Eng

Abstract

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.

Technical Summary

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.

Publications

10 25 50

publication icon
Banaji M (2010) Modelling of mitochondrial oxygen consumption and NIRS detection of cytochrome oxidase redox state. in Advances in experimental medicine and biology

publication icon
Elliott J (2010) The acute management of intracerebral hemorrhage: a clinical review. in Anesthesia and analgesia

publication icon
Elwell C (2011) Britton Chance 1913-2010 in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences

publication icon
Elwell CE (2011) Making light work: illuminating the future of biomedical optics. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

 
Description Ministerial Task Force on Organ Donation (Smith)
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact 14 recommendations aimed to increase organ donation rates in the UK by 50% in 5 five years
 
Description Neurocritical care stakeholders group (Smith)
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Chaired group. Developed quality standards for providers/commissioners of neurocritical care services
 
Description Pan London Academic Anaesthesia Training Advisory Group (Smith)
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Chair group. Development of training in academic anaesthesia and intensive care medicine in the five London schools of anaesthesia
 
Description Royal College of Physicians Neurology Services in District Hospitals (Smith)
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact Evidence provided on neurocritical care presented to working group on standards in national neurology services
 
Description Training Programme Director Academic Clinical Fellows in Anaesthesia & Critical Care UCL (Smith)
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Coordination of local programme and provision of academic support to ten Academic Clinical Fellows
 
Description Welsh Neuroscience Review Expert Group (Smith)
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact Reviewed neurosciene provision in Wales and recommendeed consolidation of services in regional centres with established clinical pathways from sateillite neuroscience centres
 
Description Central and East London NIHR Comprehensive Local Research Network Flexibility and Sustainability funding
Amount £50,856 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2010 
End 03/2011
 
Description Comprehensive Biomedical Research Centre Funding UCLH/Comprehensive Biomedical Research Centre UCLH
Amount £50,856 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Public
Country United Kingdom
Start 04/2010 
End 03/2011
 
Description Healthcare Technology Challenges for Engineering
Amount £999,578 (GBP)
Funding ID EP/K020315/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 07/2013 
End 06/2016
 
Description MRC Clinical Fellowship
Amount £100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2012
 
Description MRC Confidence in Global Mental Health Research
Amount £232,407 (GBP)
Funding ID 4373 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2018 
End 09/2019
 
Description MRC Programme Grant
Amount £1,900,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2008 
End 09/2013
 
Description NIAA
Amount £10,000 (GBP)
Organisation Neuroanaesthesia Society of Great Britain and Ireland (NASGBI) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2013 
End 03/2013
 
Description NIHR Efficacy and Mechanisms Evaluation (Co-App)
Amount £1,002,385 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2012 
End 04/2015
 
Description NIHR Efficacy and Mechanisms Evaluation Programme (Co_App)
Amount £1,002,385 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2012 
End 04/2015
 
Description Research Career Development Fellowship
Amount £528,536 (GBP)
Organisation Administrative Department of Science, Technology and Innovation (Colciencias) 
Sector Public
Country Colombia
Start 01/2009 
End 12/2014
 
Description Simon' Foundation
Amount £450,000 (GBP)
Organisation Simons Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2012 
End 12/2014
 
Description UCL Neuroscience ZNZ Collaboration
Amount € 8,600 (EUR)
Organisation UCL Neuroscience ZNZ Collaboration 
Sector Academic/University
Country United Kingdom
Start 06/2013 
End 06/2014
 
Description Wellcome Trust Project Grant (Integrating monitoring and modelling for real-time tracking of cerebral circulation and metabolism)
Amount £228,997 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2010 
End 03/2012
 
Description Centre for Space Medicine UCL 
Organisation University College London
Department Centre for Space Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to multidisciplinary workshop on innovations in Space Medicine
Collaborator Contribution Networking with other life science researchers and funders of space related research in life sciences
Impact Funding application submitted Nov 2012. Multidisciplinary involving solar physics, data mining, psychology, MRI
Start Year 2012
 
Description Risk Adjustment in Neurocritical Care (RAIN) 
Organisation National Institute of Environmental Health Sciences
Country United States 
Sector Academic/University 
PI Contribution Dr. Martin Smith is a co-applicant and steering committee member. Outcome data is contributed
Impact Multidisciplinary: clinical, statistics, epidemiology Still pending final results
Start Year 2009
 
Description A-level study day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Elwell has given an interactive talk to 1000 A'level physics students to demonstrate how medical physicists are developing new technologies and methods monitoring brain injury on neurocritical care

increased recruitment to undergraduate degree courses
Year(s) Of Engagement Activity 2009
 
Description Edinburgh Science Festival 2010 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Over 50,000 attendess for the whole festival with a sell out for the Blood Bar. Over 500 children had hands on experience of the exhibit

I have been asked back to the Edinburgh Festival for 2011 and been invited to expand the Blood Bank to include live demonstrations of NIRS for the children. I have also been asked to provide a popular talk on biomedical optics for the general public at the festival.
Year(s) Of Engagement Activity 2010
 
Description Edinburgh Science Festival 2011 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact The successful children's Blood Bar 2010 event was repeated in 2011. It was complemented by a hands on demonstration where children took part in a real life in vivo optics research study accompanied by blog and publication (targeted for 2012). An evening public lecture on Biomedical Optics was given to target an older audience.

Asked to sit on a scientific advisory board for a large scale optics/exercise event on Arthur's Seat as part of the 2012 Edinburgh Festival (the real one not the science one). The event doubles as Scotland's contribution to the 2012 Cultural Olympiad.
Year(s) Of Engagement Activity 2011
 
Description Girls in Engineering Masterclass 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact Hosted 80 girls interested in Engineering. Spent day in presentations and demonstrations

Follow up emails and applications for degree according to UCAS forms
Year(s) Of Engagement Activity 2012
 
Description I'm a Scientist - Get me Out of Here 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Web based competition to encourage schoolchildren to engage directly with scientists.

Schoolchildren sparked to think about what scientists actually do. Follow up questions on different science topics
Year(s) Of Engagement Activity 2010
 
Description Interview on BBC Radio 4 Woman's Hour 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interview on BBC Radio 4 Woman's Hour in recognition of Prof Elwell's nomination for 2016 Women in Science and Engineering Research Award - which she went on to win.
Profile for projects
Year(s) Of Engagement Activity 2016
URL https://t.co/jggRPOMh54
 
Description La Swap 6th Form college talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact Spoke to 6th Form students about Medical Physics prompting discussion about career choices

Request to speak again at next year's event
Year(s) Of Engagement Activity 2012
 
Description MP:scientist exchange ( 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Policymakers/politicians
Results and Impact A one-to-one relationship was built up with a new MP, Stephen Metcalfe, who sits on the House of Commons Science and Technology Select Committee. Three visits were made through 2010 and 2011.

Demonstrated how cutting edge research can be explained in simple chemistry and physics experiments. Some of these were optics studies relevant to this grant. The select committee subsequently launched an inquiry into school science experiments. The government accepted some (but not many!) of the committee's recommendations.
Year(s) Of Engagement Activity 2010,2011
 
Description Medical Physics Taster Course and Masterclass 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Schools
Results and Impact Over 120 students attended two events aimed at encouraging students to consider degrees in Medical Physics and Bioengineering

Increase in degree applications, follow emails from students interested in more information
Year(s) Of Engagement Activity 2012
 
Description Research Update for UCLH/UCL R&D Staff 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Rsearch group update to 20 non-clinical memebrs o teh UCLH/UCL R&D department as pat of an on-going programme

Feedback to R&D staff about projects that they have been/are invovled with.
Year(s) Of Engagement Activity 2011
 
Description SNACC Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Prof Clare Elwell was invited to deliver the Maurice Albin Lecture at the 2016 Society for Neuroanesthesia and Neurocritical Care meeting in Chicago
Year(s) Of Engagement Activity 2016
URL http://www.snacc.org/wp-content/uploads/2016/06/SNACC-Summer2016-newsletter-spanish.pdf
 
Description School visits 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Elwell has undertaken numerous visits to both primary and secondary schools. Cooper has talked to visiting schools at the University of Essex.

Raising profile of medical physics developments and collaborations with clinical sciences
Year(s) Of Engagement Activity 2009
 
Description Science Superheroes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Schools
Results and Impact 950 GCSE students attended talk on "From Marie Curie to 21st Century Medical Physics"
Talk was given on two occasions in 2012 reaching over 1800 students

Usual impact includes increased interest in Medical Physics degree course, as quoted on UCAS application forms
Year(s) Of Engagement Activity 2012
 
Description Suffrage Science 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Provided career inforamtion and interview for inclusion in publication for release in Spring 2013

TBC
Year(s) Of Engagement Activity 2012
 
Description TV Show 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact TV filming for BBC production for national broadcast in Jan 2013

Networking with other researchers and science communicators
Year(s) Of Engagement Activity 2012
 
Description UCL Summer School 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact Presentation to Year 11 students about careers in physics and engineering.

Extremely positive feedback on an inspiring talk

Extremely positive feedback on an inspiring talk

Students asked speaker to write an autobiography!
Year(s) Of Engagement Activity 2013