Diversity in blood flow control of the brain: moving from individualized modelling towards personalized treatment of the injured brain.

Lead Research Organisation: University of Leicester
Department Name: Cardiovascular Sciences

Abstract

The brain, more than any other organ in the body, requires a constant supply of blood in order to maintain its function. When blood pressure drops, small arteries dilate to restore flow levels, and when pressure rises, they constrict to protect the most delicate blood vessels and avoid bleeding in the brain. This control system can however become impaired for example following stroke, head trauma, in dementia or following premature birth and this has been associated with worse outcomes for the patient. Failure of the control system also has important implications for the management of patient's blood pressure: changes in blood pressure could be dangerous without the protection of this 'autoregulatory' system.
This project aims to improve methods for measuring cerebral autoregulation and to gain a deeper understanding of the complex relationship between blood pressure and blood flow in healthy individuals and patients following stroke. While much work has been done in this field, experimental and technical challenges in assessing the control function has so far led to only limited benefit to patients. The control system is highly complex and, typical of such biological systems, there are multiple complementary physiological mechanisms working in parallel. There are indications that even in healthy individuals there are differences in the manner and the extent to which they control the flow. Impairment may also affect different mechanisms to a varying extent in different individuals. This has important implications for grading an individual's autoregulation, as the conventional approach, based on a single number to quantifying the strength of autoregulation, is likely to be inadequate.
This project sets out in a new direction for the field, by focussing on the diversity of ways in which brain blood flow may operate in different individuals, rather than studying average group behaviour, which has so far been the predominant approach. It also breaks new ground methodologically by integrating the study of blood flow control with that of blood pressure control, based on the complementary roles these have in ensuring that the brain receives sufficient blood.
We will thus investigate a sample of healthy volunteers in detail. We will repeatedly record blood pressure and flow, heart-rate and carbon dioxide levels during spontaneous fluctuations at rest, and during challenges in a range of protocols (periodic squatting, raising the upper body of volunteers, applying random pressure changes to a cuff around the thighs, breathing air with 5% CO2). Using advanced data analysis methods (signal processing and mathematical modelling), some of which will be developed and optimized as part of this project, we will quantify the simultaneous control of blood pressure and flow and aim to identify characteristic differences between individuals and sub-groups.
Building on the differences observed in the healthy subjects, we will also study a group of patients during the first days and weeks after they have suffered a stroke. We aim to quantify the impairments in blood flow and blood pressure control, with a view to improving understanding of the evolution of this condition, and how this might impact the management of their blood pressure in the acute and chronic phase. Correct functioning of these control systems is thought to be key in making effective clinical decisions, but currently there are no clear guidelines due to a lack of understanding of the impairments in each individual patient and also the methods for their measurement.
The overarching aim of this multicentre and multidisciplinary project is thus to lay the foundations for a personalized approach to managing blood pressure control after stroke, based on characterising individuals' blood pressure and flow control, and thus to protect patients' brains from further damage.

Publications

10 25 50
 
Description The Research Associate in Leicester to work on this award commenced in post on 01 Mar 2014, though then moved to a new position (recorded in the appropriate section). A new Research Associate has been appointed. They have continued to meet the objectives of the project, including:
1. REC and Trust approvals for the Leicester component of the project related to Stroke patients and healthy controls.
2. Website development.
3. Database development.
4. Investigator meetings to ensure uniformity in study protocol, and data collection and analysis.
5. Healthy volunteer and patient recruitment.
6. Generation of scientific outputs from the database (recorded in the publications section).

A full report on the project progress in Leicester, Oxford and Southampton will be provided by Professor David Simpson for the Lead Institution, University of Southampton.
Exploitation Route The brain, more than any other organ in the body, requires a constant supply of blood in order to maintain its function. When blood pressure drops, small arteries increase in size to restore flow levels, and when pressure rises, they narrow to protect the most delicate blood vessels and avoid bleeding and swelling in the brain. Failure of this control system (called cerebral autoregulation) following brain injury can lead to worse outcomes, and also influence the management of changes in blood pressure. This project aims to improve methods for measuring cerebral autoregulation and to gain a deeper understanding of the complex relationship between blood pressure and blood flow in healthy individuals as well as in patients following stroke.

We are actively recruiting all patients providing consent (or legal representative consent), as soon as possible after stroke onset, undertaking six assessments of blood pressure, heart rate, and brain blood flow in total. These assessments will be taken at rest, and in response to movement of the arm and during breathing a 5% concentration of carbon dioxide (the body's waste gas). Up to 5 of these assessments will be in the acute stroke phase, up to 72 hours from stroke onset (at 9, 12, 24 and 48 hours, depending on how soon after stroke you were admitted). The last two assessments will carried out in the subacute phase (within 2 weeks) and in the chronic phase (at 3 months after your stroke).

By recruiting all patients, i.e. having very few reasons to exclude patients, we aim to quantify all impairments in blood flow and blood pressure control using advanced data analysis methods, with a view to improving understanding of how this might impact on the management of an individual patient's blood pressure in the acute and chronic phases following stroke. In turn, this will impact on the future treatment of this common clinical problem in acute stroke.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare

 
Description Intercalated BSc Programme
Amount £1,000 (GBP)
Organisation University of Leicester 
Sector Academic/University
Country United Kingdom
Start 08/2017 
End 06/2018
 
Title Validating the measurements of cerebral autoregulation 
Description A paper on the statistical criteria for estimation of cerebral autoregulation has just been published. It outlines a new criterion for analysing and evaluating the data that we have recently gathered. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2016 
Provided To Others? Yes  
Impact N/A 
 
Title Leicester Cerebral Haemodynamics Database 
Description We have a longstanding research interest in cerebral haemodynamics in health and disease, including stroke, in Leicester. This includes the use of spontaneous blood pressure changes, motor paradigms (active, passive, imagined), and changes in carbon dioxide tension (hypocapnia, hypercapnia) in the assessment of cerebral auto regulation, cerebrovascular reactivity and neuromuscular coupling. The data generated from this project in respect of TCD assessment of cerebral haemodynamics have been added to the database. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact An initial publication of normative data has been produced, and added to the publications section. Additional publications are planned with respect to the stroke patients, including the influences of stroke severity, stroke subtype and thrombolysis on cerebral haemodynamics. 
 
Title The Leicester Cerebral Haemodynamics Database 
Description The Leicester Cerebral Haemodynamics Database has been created from the archives of the research teams past work and studies. It contains data on several subgroups (healthy volunteers, ischaemic stroke patients, Parkinson patients) that are being further analysed by our research team and the collaborators previously mentioned. The interim analysis on the stroke database will be presented at European Stroke Organisation Conference 2016, Barcelona. Further analysis will be published later in the year. A database containing the recordings of all the ectopic beats and arrhythmia is being investigated for the best methods off analysis and data extraction. 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact The two recent research papers, written as a consequence of this database ('The Leicester cerebral haemodynamics database: normative values and the influence of age and sex' and 'Statistical criteria for estimation of the cerebral autoregulation index (ARI) at rest') has been recognised by the journal as Physiological Measurement Highlights of 2016. Also, the database has been shared with other groups and has created the following output: Liu J, Simpson DM, Kouchakpour H, Panerai RB, Chen J, Gao S, Zhang P, Wu X 2014 Rapid pressure-to-flow dynamics of cerebral autoregulation induced by instantaneous changes of arterial CO2. Medical Engineering & Physics 36:1636-1643. Angarita-Jaimes N, Kouchakpour H, Liu J, Panerai RB, Simpson DM 2014 Optimising the assessment of cerebral autoregulation from black box models. Med Eng & Phys 36:607-612. Liu J, Koochakpour H, Panerai RB, Katsogridakis E, Wang Z, Simpson DM 2013 Tracking instantaneous pressure-to-flow dynamics of cerebral autoregulation induced by CO2 reactivity. Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:3929-3932. Fan L, Bush G, Katsogridakis E, Simpson DM, Allen R, Potter J, Birch AA, Panerai RB 2013 Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function. Med Biol Eng Comput. 51:709-718. 
 
Description CARNet Organisation 
Organisation The Cerebral Autoregulation Research Network
Country Unknown 
Sector Learned Society 
PI Contribution The Cerebral Autoregulation Research Network (CARNet) is a non-profit organisation comprised of approximately 100 scientists from approximately 12 different countries, with the aim to provide a framework for collaboration and exchange of ideas in the field of human cerebrovascular research.
Collaborator Contribution Participants of the EPSRC grant, in Leicester, Southampton and Oxford (Grant Collaborators) have been instrumental in the founding of CARNet and have acted in different roles in its steering committee, in the organisation of annual conferences, in collaborative multi-centre projects and in joint publications.
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling. The first outputs to this collaboration from our group are: (1) an overview of the variations in the transfer function technique as it is used in the scientific literature to assess dynamic CA for spontaneous oscillations in BP and CBFV; (2) the assessment of the variability that may occur in the collaborators analytical methods to the same data set; (3) the publication of the white paper detailing and standardising the research techniques used in the field of cerebral autoregulation. Meel-van den Abeelen ASs, can Beek AH, Slump CH, Panerai RB, Claassen JA 2014 Transfer function analysis for the assessment of cerebral autoregulation using spontaneous oscillations in blood pressure and cerebral blood flow. Med Eng & Phys 36:563-575. Meel-van den Abeelen, A. S. S., Simpson, D. M., Wang, L. J. Y., Slump, C. H., Zhang, R., Tarumi, T., Rickards, C. A., Payne, S., Mitsis, G. D., Kostoglou, K., Marmarelis, V., Shin, D., Tzeng, Y. C., Ainslie, P. N., Gommer, E., Muller, M., Dorado, A. C., Smielewski, P., Yelicich, B., Puppo, C., Liu, X. Y., Czosnyka, M., Wang, C. Y., Novak, V., Panerai, R. B., Claassen, J. A. H. R. 2014, Between-centre variability in transfer function analysis, a widely used method for linear quantification of the dynamic pressure-flow relation: The CARNet study, Medical Engineering & Physics, 36, pp. 620-627. Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network. Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB; international Cerebral Autoregulation Research Network (CARNet). J Cereb Blood Flow Metab. 2016 Jan 18. pii: 0271678X15626425. [Epub ahead of print] Review. PMID: 26782760
Start Year 2011
 
Description Diversity on Blood Flow Control to the Brain 
Organisation University Hospital Southampton NHS Foundation Trust
Country United Kingdom 
Sector Hospitals 
PI Contribution We are responsible for providing acute stroke patients and healthy controls, as well as expertise in data analysis, to meet the following project objectives: 1. To propose and test simple bedside methods for the integrated multi-dimensional assessment of cardiovascular (baroreceptor) and cerebrovascular (cerebral autoregulation) control. 2. To evaluate the diversity of autoregulatory responses of healthy subjects in anticipation that these reflect real individual differences in physiological strategies for brain blood flow control rather than random error. 3. To evaluate the diversity of autoregulatory responses of a stroke population during the acute (<72 hours), subacute (2 weeks) and chronic (3 months) phases of stroke. 4. To develop a grading system which takes into account the interaction of multiple individual cerebro- and cardiovascular parameters, using data collected from both populations, and therefore: a. To develop a scale to differentiate between a healthy and impaired system, based on the interaction between control systems. b. To extend these scales to patients with concomitant comorbidity (e.g. atrial fibrillation) that excluded them from previous studies in order to move towards future personalised care. 5. To develop further studies to use this system for informing future management decisions in the acutely unstable stroke patient population and assess if these methods provide clinically meaningful results for the management of these patients.
Collaborator Contribution Our partners have focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls (University of Southampton, University Hospital Southampton NHS Trust), and data analysis and individualised modelling (Universities of Southampton and Oxford).
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling.
Start Year 2013
 
Description Diversity on Blood Flow Control to the Brain 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We are responsible for providing acute stroke patients and healthy controls, as well as expertise in data analysis, to meet the following project objectives: 1. To propose and test simple bedside methods for the integrated multi-dimensional assessment of cardiovascular (baroreceptor) and cerebrovascular (cerebral autoregulation) control. 2. To evaluate the diversity of autoregulatory responses of healthy subjects in anticipation that these reflect real individual differences in physiological strategies for brain blood flow control rather than random error. 3. To evaluate the diversity of autoregulatory responses of a stroke population during the acute (<72 hours), subacute (2 weeks) and chronic (3 months) phases of stroke. 4. To develop a grading system which takes into account the interaction of multiple individual cerebro- and cardiovascular parameters, using data collected from both populations, and therefore: a. To develop a scale to differentiate between a healthy and impaired system, based on the interaction between control systems. b. To extend these scales to patients with concomitant comorbidity (e.g. atrial fibrillation) that excluded them from previous studies in order to move towards future personalised care. 5. To develop further studies to use this system for informing future management decisions in the acutely unstable stroke patient population and assess if these methods provide clinically meaningful results for the management of these patients.
Collaborator Contribution Our partners have focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls (University of Southampton, University Hospital Southampton NHS Trust), and data analysis and individualised modelling (Universities of Southampton and Oxford).
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling.
Start Year 2013
 
Description Diversity on Blood Flow Control to the Brain 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution We are responsible for providing acute stroke patients and healthy controls, as well as expertise in data analysis, to meet the following project objectives: 1. To propose and test simple bedside methods for the integrated multi-dimensional assessment of cardiovascular (baroreceptor) and cerebrovascular (cerebral autoregulation) control. 2. To evaluate the diversity of autoregulatory responses of healthy subjects in anticipation that these reflect real individual differences in physiological strategies for brain blood flow control rather than random error. 3. To evaluate the diversity of autoregulatory responses of a stroke population during the acute (<72 hours), subacute (2 weeks) and chronic (3 months) phases of stroke. 4. To develop a grading system which takes into account the interaction of multiple individual cerebro- and cardiovascular parameters, using data collected from both populations, and therefore: a. To develop a scale to differentiate between a healthy and impaired system, based on the interaction between control systems. b. To extend these scales to patients with concomitant comorbidity (e.g. atrial fibrillation) that excluded them from previous studies in order to move towards future personalised care. 5. To develop further studies to use this system for informing future management decisions in the acutely unstable stroke patient population and assess if these methods provide clinically meaningful results for the management of these patients.
Collaborator Contribution Our partners have focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls (University of Southampton, University Hospital Southampton NHS Trust), and data analysis and individualised modelling (Universities of Southampton and Oxford).
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling.
Start Year 2013
 
Description Grant Collaborators 
Organisation University Hospital Southampton NHS Foundation Trust
Country United Kingdom 
Sector Hospitals 
PI Contribution We are responsible for collecting and providing physiological measurements (cerebral haemodynamics, blood pressure, ECG, respiratory CO2 levels) on healthy controls and acute ischaemic stroke patients. These data can be used to give estimates on the cerebral autoregulation integrity. We have also collated, organised and provided a database that contains all the physiological measurements that our research team has gathered in previous years. These data will be shared with our Grant Collaborators from the University of Southampton and University of Oxford. We have used the database to provide the normative values of subpopulations and various demographics. It has also been used for further statistical analysis that has established robust confidence limits to the modelling that is used in estimating cerebral autoregulation. Our experience and expertise in analysing such multivariate data is also being used to establish the key parameters that can identify patterns of recovery following stroke and to provide meaningful results for the management of these patients.
Collaborator Contribution Our partners focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls. Based on the data that we provide to them, they give expertise in data analysis, optimisation of analysing methods and integrated modelling, aiming to develop tools that can support individualised patient care.
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling. There have been several outputs in recent years that have focused on optimisation of the analytical methods and modelling used to determine cerebral autoregulation. This grant is a continuation of this work with specific objectives. Liu J, Simpson DM, Kouchakpour H, Panerai RB, Chen J, Gao S, Zhang P, Wu X 2014 Rapid pressure-to-flow dynamics of cerebral autoregulation induced by instantaneous changes of arterial CO2. Medical Engineering & Physics 36:1636-1643. Angarita-Jaimes N, Kouchakpour H, Liu J, Panerai RB, Simpson DM 2014 Optimising the assessment of cerebral autoregulation from black box models. Med Eng & Phys 36:607-612. Liu J, Koochakpour H, Panerai RB, Katsogridakis E, Wang Z, Simpson DM 2013 Tracking instantaneous pressure-to-flow dynamics of cerebral autoregulation induced by CO2 reactivity. Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:3929-3932. Fan L, Bush G, Katsogridakis E, Simpson DM, Allen R, Potter J, Birch AA, Panerai RB 2013 Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function. Med Biol Eng Comput. 51:709-718.
Start Year 2013
 
Description Grant Collaborators 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We are responsible for collecting and providing physiological measurements (cerebral haemodynamics, blood pressure, ECG, respiratory CO2 levels) on healthy controls and acute ischaemic stroke patients. These data can be used to give estimates on the cerebral autoregulation integrity. We have also collated, organised and provided a database that contains all the physiological measurements that our research team has gathered in previous years. These data will be shared with our Grant Collaborators from the University of Southampton and University of Oxford. We have used the database to provide the normative values of subpopulations and various demographics. It has also been used for further statistical analysis that has established robust confidence limits to the modelling that is used in estimating cerebral autoregulation. Our experience and expertise in analysing such multivariate data is also being used to establish the key parameters that can identify patterns of recovery following stroke and to provide meaningful results for the management of these patients.
Collaborator Contribution Our partners focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls. Based on the data that we provide to them, they give expertise in data analysis, optimisation of analysing methods and integrated modelling, aiming to develop tools that can support individualised patient care.
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling. There have been several outputs in recent years that have focused on optimisation of the analytical methods and modelling used to determine cerebral autoregulation. This grant is a continuation of this work with specific objectives. Liu J, Simpson DM, Kouchakpour H, Panerai RB, Chen J, Gao S, Zhang P, Wu X 2014 Rapid pressure-to-flow dynamics of cerebral autoregulation induced by instantaneous changes of arterial CO2. Medical Engineering & Physics 36:1636-1643. Angarita-Jaimes N, Kouchakpour H, Liu J, Panerai RB, Simpson DM 2014 Optimising the assessment of cerebral autoregulation from black box models. Med Eng & Phys 36:607-612. Liu J, Koochakpour H, Panerai RB, Katsogridakis E, Wang Z, Simpson DM 2013 Tracking instantaneous pressure-to-flow dynamics of cerebral autoregulation induced by CO2 reactivity. Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:3929-3932. Fan L, Bush G, Katsogridakis E, Simpson DM, Allen R, Potter J, Birch AA, Panerai RB 2013 Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function. Med Biol Eng Comput. 51:709-718.
Start Year 2013
 
Description Grant Collaborators 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution We are responsible for collecting and providing physiological measurements (cerebral haemodynamics, blood pressure, ECG, respiratory CO2 levels) on healthy controls and acute ischaemic stroke patients. These data can be used to give estimates on the cerebral autoregulation integrity. We have also collated, organised and provided a database that contains all the physiological measurements that our research team has gathered in previous years. These data will be shared with our Grant Collaborators from the University of Southampton and University of Oxford. We have used the database to provide the normative values of subpopulations and various demographics. It has also been used for further statistical analysis that has established robust confidence limits to the modelling that is used in estimating cerebral autoregulation. Our experience and expertise in analysing such multivariate data is also being used to establish the key parameters that can identify patterns of recovery following stroke and to provide meaningful results for the management of these patients.
Collaborator Contribution Our partners focus on similar objectives, specifically with respect to subarachnoid haemorrhage patients and healthy controls. Based on the data that we provide to them, they give expertise in data analysis, optimisation of analysing methods and integrated modelling, aiming to develop tools that can support individualised patient care.
Impact This is a multidisciplinary collaboration between stroke physicians, neurosurgeons, medical physicists, and experts in mathematics, physics and computer modelling. There have been several outputs in recent years that have focused on optimisation of the analytical methods and modelling used to determine cerebral autoregulation. This grant is a continuation of this work with specific objectives. Liu J, Simpson DM, Kouchakpour H, Panerai RB, Chen J, Gao S, Zhang P, Wu X 2014 Rapid pressure-to-flow dynamics of cerebral autoregulation induced by instantaneous changes of arterial CO2. Medical Engineering & Physics 36:1636-1643. Angarita-Jaimes N, Kouchakpour H, Liu J, Panerai RB, Simpson DM 2014 Optimising the assessment of cerebral autoregulation from black box models. Med Eng & Phys 36:607-612. Liu J, Koochakpour H, Panerai RB, Katsogridakis E, Wang Z, Simpson DM 2013 Tracking instantaneous pressure-to-flow dynamics of cerebral autoregulation induced by CO2 reactivity. Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:3929-3932. Fan L, Bush G, Katsogridakis E, Simpson DM, Allen R, Potter J, Birch AA, Panerai RB 2013 Adaptive feedback analysis and control of programmable stimuli for assessment of cerebrovascular function. Med Biol Eng Comput. 51:709-718.
Start Year 2013
 
Description Santiago Collaboration 
Organisation University of Santiago, Chile
Country Chile 
Sector Academic/University 
PI Contribution We have collated, organised and provided a database that contains all the physiological measurements that our research team has gathered in previous years. With this database, we are responsible for providing physiological measurements (cerebral haemodynamics, blood pressure, ECG, respiratory CO2 levels) on healthy controls and acute ischaemic stroke patients. These data can be used to give estimates on the cerebral autoregulation integrity. These data will be shared with our Santiago Collaborators from the University of Santiago, Chile and it has been used for further statistical analysis to establish robust confidence limits to the modelling that is used in estimating cerebral autoregulation.
Collaborator Contribution Our collaborators have expertise in analytical methods and modelling used to determine cerebral autoregulation. By using their own analytical methods they will use the multivariate data available within the database for optimisation of analysing methods and integrated modelling, that are aimed to develop tools that can support individualised patient care.
Impact This is a multidisciplinary collaboration between Stroke physicians, Biomedical Scientists, experts in mathematics, physics and computer modelling. Some of the outputs in previous year include include: Chacón M, Jara JL, Panerai RB. A new model-free index of dynamic cerebral blood flow autoregulation. PLoS One. 2014 Oct 14;9(10):e108281. doi: 10.1371/journal.pone.0108281. eCollection 2014. This collaboration is a continuation of this work involving data generated by the current grant.
Start Year 2016
 
Description Sao Paulo Collaboration 
Organisation University of Sao Paulo
Country Brazil 
Sector Academic/University 
PI Contribution As part of this collaboration we are training young researchers from the University of Sao Paulo in research methods, data collection, analysis and interpretation applied to studies of cerebral haemodynamics in healthy and diseased subjects. These have included Dr Ricardo Nogueira (PhD, 6 months trainiing), Dr Angela Salinet (PhD, 4 years), and Mrs Juliana Ribeiro (PhD, two separate 5-6 months visits, examination passed December 2016). In addition to research outputs prepared in collaboration with these young investigators, we have also shared publications with Dr Edson Shu, head of Brazilian team, and some of his more senior colleagues.
Collaborator Contribution Our partners had acquired the physiological data on patients with impaired cerebral autoregulation and healthy controls. They contributed to discussions on suitable methods for data analysis, individualised modelling, preparation and structuring of manuscripts and finalising the publication.
Impact This is a multidisciplinary collaboration between Stroke physicians, Medical Physicists, Biomedical Scientists, Neurosurgeons, Neurologists, and Physiotherapists. A paper on the statistical criteria for estimation of cerebral autoregulation has just been published. It outlines a new criterion for analysing and evaluating the data that we have recently gathered. The normative values for the cerebral haemodynamics in healthy adults and the influence of age and gender have been submitted to Journal of Cerebral Blood Flow and Metabolism (February 2016) for publication. We are currently working on normative values for ischaemic stroke patients, which will be presented at the European Stroke Organisation Conference 2016. Other outputs include analysis of various models and methods of measuring and analysing cerebral autoregulation in healthy individuals and in stroke patients. Statistical criteria for estimation of the cerebral autoregulation index (ARI) at rest. Panerai, Ronney; Haunton, Victoria; Hanby, Martha; Salinet, Angela; Robinson, Thompson. Physiological Measurement Article reference: PMEA-101193.R1 The Leicester Cerebral Haemodynamics Database: Normative Values and the Influence of Age and Gender. Nikil Patel; Ronney B Panerai; Victoria Hauton; Emmanuel Katsogridakis; Nazia P Saeed; Angela Salinet; Nazia Syed; Fiona Brodie; Schnell D'Sa; Thompson G Robinson Submitted to: Physiological Measurement, January 2016 The Leicester Cerebral Haemodynamics Database: Normative Values of Acute Ischaemic Stroke and Subtype. Osian Llwyd; Ronney B. Panerai; Shamila Rahman; Nazia P. Saeed; Angela Salinet; Emily R. Atkins; Fiona Brodie; Thompson G. Robinson. ESOC 2016, Barcelona. Abstract number: AS23-014 The Leicester Cerebral Haemodynamics Database: Assessment of cerebral Autoregulation from Ectopic Heartbeats. Osian Llwyd; Ronney B. Panerai; Victoria Hauton, Thompson G. Robinson. Submit March 20th 2016: CARNet 2016, Boston. Salinet ASM, Robinson TG, Panerai RB 2015 Effects of cerebral ischemia on human neurovascular coupling, CO2 reactivity and dynamic cerebral autoregulation. J Applied Physiol 118:170-177. Salinet ASM, Panerai RB, Robinson TG. 2014 The Longitudinal Evolution of Cerebral Blood Flow Regulation after Acute Ischaemic Stroke. Cerebrovasc Dis Extra 4:186-197. Nogueira RC, Bor-Seng-Shu E, Santos MR, Negrao CE, Teixeira MJ, Panerai RB 2013 Dynamic cerebral autoregulation changes during sub-maximal handgrip maneuver. PLoS One Vol 8 Issue 8 e70821. Salinet ASM, Robinson TG, Panerai RB 2013 Cerebral blood flow response to neural activation after acute ischemic stroke: a failure of myogenic regulation? J Neurology 260:2588-2595. Salinet AS, Robinson TG, Panerai RB. 2013 Active, Passive and Motor Imagery Paradigms: Component Analysis to Assess Neurovascular Coupling. J Appl Physiol 114:1406-1412. Bor-Seng-Shu E, Figueiredo EG, Fonoff ET, Fujimoto Y, Panerai RB, Teixeira MJ. Decompressive craniectomy and head injury: brain morphometry, ICP, cerebral hemodynamics, cerebral microvascular reactivity, and neurochemistry. Neurosurg Rev. 2013 Feb 6. [Epub ahead of print] PubMed PMID: 23385739. Salinet AS, Haunton VJ, Panerai RB, Robinson TG. 2013 A systematic review of cerebral hemodynamic responses to neural activation following stroke. J Neurol. 260:2715-2721. Bor-Seng-Shu E, Figueiredo EG, Amorim RL, Teixeira MJ, Valbuza JS, de Oliveira MM, Panerai RB. Decompressive craniectomy: a meta-analysis of influences on intracranial pressure and cerebral perfusion pressure in the treatment of traumatic brain injury. J Neurosurg. 2012 Sep;117(3):589-96. Bor-Seng-Shu E, Kita WS, Figueiredo EG, Paiva WS, Fonoff ET, Teixeira MJ, Panerai RB. 2012 Cerebral hemodynamics: concepts of clinical importance. Arq Neuropsiquiatr 70:352-356. Salinet ASM, Panerai RB, Robinson TG. 2012 Effects of active, passive and motor imagery paradigms on cerebral and peripheral hemodynamics in older volunteers: A functional TDC study. Ultrasound in Medicine and Biology 38:997-1003 Salinet ASM, Robinson TG, Panerai RB 2012 Reproducibility of cerebral and peripheral haemodynamic responses to active, passive and motor imagery paradigms in older healthy volunteers: A fTCD study. Journal of Neuroscience Methods 206:143-150 Bor-Seng-Shu E, de-Lima-Oliveira M, Teixeira MJ, Panerai RB 2011 Predicting symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 60:E501-502.
Start Year 2009
 
Title Dynamic cerebral autoregulation modelling 
Description A suite of Fortran programmes has been developed for analysis of cerebral haemodynamic measurements, including data editing, transfer function analysis, time-domain modelling and coherent averaging. This software has been shared with collaborators in different international centres. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact The software has supported data analysis in the current grant and associated studies in the field of cerebral haemodynamics in health subjects and patients with stroke. 
 
Description Brain Awareness Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact As part of the international event, Brain Awareness Week, the research group took part in a University led open day, Brain Awareness Day, that targeted secondary school students and the general public. We disseminated the main aims and objectives of our research by presenting posters and conducting small group discussions.
Year(s) Of Engagement Activity 2016,2017
 
Description Cerebral Autoregulation Network (CARNet) Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral and poster presentations to the conference attendees about research findings that was created as a direct outcome from this grant.
Year(s) Of Engagement Activity 2016,2017
URL http://www.car-net.org/content/meetings
 
Description City Ride Leicester Health and Science Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Engagement with the public in a science fair that was running alongside a 8km bicycle festival within the city of Leicester. The research group disseminated the area of science we are working on through presentation of posters and a water activity. The activity included a demonstration of the mechanics of blood flow (colored water) when it passes from the heart (a plastic bottle) to other organs of the body through healthy arteries (wide tube) and diseased arteries (narrow tube). The public/children were encouraged to race and time the flow rate of the blood when using different arteries and describe the fluid flow/pressure leaving the arteries.
Year(s) Of Engagement Activity 2017
URL https://www.letsride.co.uk/city-ride/leicester
 
Description International Stroke Conference - ESOC 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented poster to the conference attendees about some of our findings from the database that was created as a direct outcome from this grant.
Year(s) Of Engagement Activity 2016
URL http://www.esoc2016.com/
 
Description RB Panerai - invited speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited speaker, San Diego, April 2014
Year(s) Of Engagement Activity 2014
 
Description Royal Society Autoregulation Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk 'Cerebrovascular Dysautoregulation in Acute Stroke: Implications for the Management of Haemodynamic Perturbations'.

Excellent 2-day meeting with each disease section including methodological development, preclinical and clinical aspects; I participated with the clinical aspects of the stroke section.
Year(s) Of Engagement Activity 2018
 
Description T Robinson - invited external speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited external speaker, CARNet 2015 conference, Southampton, July 2015
Year(s) Of Engagement Activity 2015
 
Description World Stroke Congress 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented poster to the conference attendees about some of the research findings in the database that was created as a direct outcome from this grant.
Year(s) Of Engagement Activity 2016
URL http://wsc.kenes.com/