Cerebral Haemodynamics in Ageing and Stroke Medicine

Cerebral Haemodynamics in Ageing and Stroke Medicine

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CHiASM MembersGroup Members

Karen Appiah, Hardeep S. Aujla, Caroline Banahan, Juliana Caldas Ribeiro Bittencourt, Emma Chung, Max Chacon, Alice C. Durham, Kaza Evangelia, Claire L. Gibson, Victoria Haunton, Man Lam, Osian Llwyd, Jatinder Minhas, Amit Mistri, Ronney Panerai, Kumar Ramnarine, Thompson G. Robinson.

Summary

Researchers in the CHiASM group combine clinical research with experiments in healthy volunteers, in vitro studies, and mathematical models to develop our understanding of cerebral haemodynamics in health, ageing and disease. In addition to studies of dementia and Parkinson’s disease, a major research focus of our group is Stroke. Stroke is the second leading cause of death in the world resulting in 6.7 million deaths each year. The burden of disease (disability, illness and premature deaths) caused by stroke is set to double worldwide by 2030. The CHIASM group’s research interests include the development of novel ultrasound methods for the detection of brain injury, development of novel biometrics for assessing carotid plaque vulnerability (a major cause of stroke), ultrasound embolus detection, and detection of impaired cerebral autoregulation. The aim of our research is to develop novel diagnostic imaging, physiological measurements, and interventions for patient benefit.

CHiASM Research

Cerebral Haemodynamics and Autoregulation

The group use an array of laboratory techniques and mathematical models to research and develop the field of cerebral haemodynamics. Using acute neuroimaging techniques (mainly Ultrasound and MRI) the groups’ main research interest is the cerebral autoregulatory (CA) system.  A mechanism that continuously adjusts the diameters of arteries in response to the metabolic demands of brain tissue or fluctuations in blood pressure.  This ensures an adequate supply of oxygenated blood is maintained to the brain and it protects brain tissue from receiving too much or too little blood flow.  In the absence of CA there would be a tendency for individuals to lose consciousness when changing posture, or for capillaries to rupture during exercise.

Stroke Medicine

Stroke is the second single most common cause of death in the world causing 6.7 million deaths each year. The burden of disease (disability, illness and premature deaths) caused by stroke is set to double worldwide by 2030. The CHIASM group’s research interests include the study of cerebral haemodynamics, and in particular the impact of changes in cerebral haemodynamic control mechanisms on the management of blood pressure, blood pressure variability and other physiological perturbations following acute stroke. We also collaborate with basic researchers using experimental models of stroke.

Further information on our latest work and projects can be found in the links below.

Current research includes:

 

Cardiovascular Research Centre imageBRU and Translational Medicine Facility imageDavid Wilson Biobank imagevan Geest Biomarker Facility image

Cerebral Autoregulation

Impaired regulation of cerebral blood flow is implicated in a number of clinical conditions, such as ischaemic stroke, severe head injury, liver failure, diabetes, autonomic nervous system failure, carotid artery disease, dementia, pre-eclampsia and neonatal prematurity. In the last 20 years, investigators in the UHL Department of Medical Physics and University of Leicester Department of Cardiovascular Sciences, led by Professors Thompson G Robinson and Ronney Panerai, and Dr Victoria Haunton have worked in collaboration with several clinical specialties in pioneering new techniques for assessment of cerebral autoregulation in a clinical setting.

The cerebral autoregulatory (CA) system continuously adjusts the diameters of arteries in response to the metabolic demands of brain tissue to maintain an adequate supply of oxygenated blood to the brain by compensating for changes in blood pressure and carbon dioxide (CO2) levels. This protects brain tissue from receiving too much or too little blood flow. In the absence of CA there would be a tendency for individuals to lose consciousness when changing posture, or for capillaries to rupture during exercise.


New Protocol for Assessing Dynamic Cerebral Autoregulation

The dynamic response of cerebral blood flow to sudden changes in blood pressure (BP), or blood CO2 levels, can be assessed using the sudden release of thigh cuffs to disturb mean BP, or inhalation of CO2. Our team recently showed that the combination of spontaneous fluctuations in BP and CBF, coupled with novel signal processing techniques, can provide indices of dynamic CA, as long as sufficient variability in BP is present. To guarantee BP variability and allow widespread use of this approach by the patient's bedside, the EPSRC funded a project in Leicester to design and test a computer controlled system to increase BP variability using a 'pseudo-random binary sequence' for inflation and deflation of a pair of thigh cuffs. This technique can also be used to control administration of CO2 gas, which greatly enhances it's clinical usefulness.

Hardware and software components were designed and constructed by the Clinical Engineering group (Mr. Glen Bush and Dr Lingke Fan) and validation and testing of the device were performed by Emmanouil Katsogridakis as part of his PhD, which was recently awarded a 2012 Best PhD Prize by the University of Leicester College of Medicine, Biology and Psychology.

 

Multivariate System Identification of Neurovascular Coupling

Neurovascular coupling (NVC) describes the ability of the cerebral circulation to adjust to changes in metabolic demand when the brain is stimulated by motor, sensory or cognitive paradigms. This study investigates NVC in acute stroke patients, in collaboration with the Department of Cardiovascular Sciences Stroke Medicine group led by Professor TG Robinson. This project led to the recent development of a multivariate system for identifying the response of cerebral blood flow to motor stimulation of the upper limb, together with the contributions of arterial BP and blood CO2 levels. Using this approach, a single recording during motor stimulation yields the principal parameters describing NVC, together with dynamic cerebral autoregulation measurements, and quantification of vascular reactivity to CO2. In her PhD thesis, Angela Salinet applied this new approach in an innovative study of the natural history of dynamic CA and NVC in stroke patients.

 

Assessment of Cerebral Autoregulation with Magnetic Resonance Imaging

The introduction of transcranial Doppler ultrasound (TCD) in the early 80’s revolutionised the study of cerebral haemodynamics when compared to other techniques for measuring cerebral blood flow, but, a major limitation of TCD is that cerebral blood flow can only be estimated in the major cerebral arteries. This limitation is particularly critical in conditions such as stroke or traumatic head injury where there is likely to be regional impairment of cerebral blood flow. To improve the spatial resolution of dynamic CA assessment, the UK Stroke Association has funded a highly innovative project to obtain estimates of dynamic CA using MRI (led by Prof. TG Robinson, Dr. MA Horsfield and Prof. RB Panerai).

Transcranial Ultrasound

A major cause of stroke comes from embolic debris (thrombus, bubbles and pieces of plaque) that travel through the cerebral circulation and become lodged in arteries supplying the brain. Our research group has extensive expertise in the detection and characterisation of cerebral emboli using transcranial Doppler ultrasound. Recent advances include the development of software to estimate the sizes of air bubbles entering the cerebral circulation during cardiac surgery, use of 'virtual patient' simulations to estimate the impact of bubbles on cerebral blood flow, and development of digital MR subtraction software to assist Radiologists in identifying new embolic lesions. We are also investigating the potential for using an acoustic radiation force to deflect emboli away from the brain and to distinguish solid emboli from bubbles.

Detection and deflection of emboli in the bloodstream

This Engineering and Physical Sciences Research Council (EPSRC) study (P.I. Dr Emma Chung) is investigating the feasibility of using an ultrasound acoustic radiation force to deflect emboli away from vital organs, such as the brain, during surgery. We are also investigating whether differing responses of solid and gas emboli to an acoustic radiation force could provide a reliable method for distinguishing between harmful solid emboli and benign gas bubbles.

Brain injury during heart surgery

This British Heart Foundation (BHF) study (P.I. Dr Emma Chung) was the first to determine the size distribution of bubbles and volume of air entering the cerebral circulation during heart surgery. We compared the incidence, timing, and properties of bubbles released into the bloodstream during surgery with brain injury assessed using MRI and cognitive testing and found no links between the number or sizes of bubbles and brain injury. The PhD student who performed this study, Dr Nikil Patel, was awarded a College PhD prize and the results of this study were published on the cover of Stroke.

Modelling embolic stroke

This collaboration with Open University theoretical physicist, Dr Jim Hague, led to development of the first computational model of embolic stroke. Our 'virtual patient' simulations are capable of taking information about the size and composition of emboli experienced intraoperatively to provide real-time estimates of the likely impact of emboli on cerebral blood flow.

Carotid Plaque Imaging

Researchers in Medical Physics have collaborated on the development and clinical applications of a number of medical ultrasound imaging techniques including: contrast enhanced imaging; Tissue Doppler Imaging; greyscale image processing; vector Doppler flow imaging; multigate Doppler; shear wave elastography. These enable the measurement of various vascular and physiological parameters with high temporal and spatial resolution. Well equipped labs and ultrasound facilities are available with our collaborators. For example the measurement of flow mediated dilation for assessing endothelial function supports clinical studies in the Department of Cardiovascular Sciences and the Leicester Diabetes Centre. For more information please contact Dr Kumar Ramnarine.

Assessment of Unstable Carotid Plaque

Shear Wave Elastography (SWE)One important clinical application is the use of novel ultrasound techniques to help identify the unstable carotid plaque. A common cause of stroke comes from the build-up of plaque within the carotid artery in the neck. The current process for deciding which patients should be offered surgery to remove the plaque is heavily reliant on ultrasound measurement of blood flow velocity, which is used as a surrogate measure for estimating the degree of narrowing of the artery (stenosis). The degree of stenosis, however, is a poor predictor of individual stroke risk.

In Leicester we are involved in the search for more reliable markers of plaque instability, which we hope will improve clinical decision making for patients with carotid artery disease. Medical Physics researchers work in collaboration with Vascular Surgeons, Stroke Physicians and Clinical Vascular Scientists to develop and evaluate new ultrasound techniques that could help to identify individual patients at risk of plaque rupture by assessing the ultrasonic appearance, dynamic behaviour and elasticity of the plaque. We have acquired a state-of-the-art Supersonic Imagine Aixplorer ultrasound system that utilises a novel technique known as shear wave elastography for assessment of tissue stiffness. Shear wave elastography directly measures Young's Modulus by using ultrafast ultrasound imaging techniques to map the speed of propagation of ultrasonic shear-waves through tissue. We were one of the first centres to investigate possible vascular applications and the first to demonstrate potential clinical benefit to help identify the unstable carotid plaque.

Experimental ultrasound studies

In Leicester we combine clinical in-vivo studies with experimental in-vitro studies to help assess the clinical potential of new ultrasound techniques. Experimental phantoms, test objects, flow models and tissue mimics enable the assessment of novel ultrasound techniques under well controlled laboratory conditions. Researchers in Leicester have developed ultrasound phantoms, test objects and tissue mimicking materials that are well characterised and have been widely adopted in research laboratories worldwide.

For more information please contact Dr Kumar Ramnarine

 

Brain Magnetic Resonance Imaging (MRI)

Brain MRI research conducted by our team focuses on using MRI techniques to image the arteries supplying the brain and improve the detection and quantification of brain injuries. We work closely with Neuroradiologists, Clinicians, and Scientists in developing novel imaging techniques and to support the interpretation and analysis of MRI scans for clinical research studies.

Detection of subtle changes to the brain using MRI

As we get older, there are often subtle changes in the brain, due to small pieces of debris (emboli) becoming lodged in the cerebral arteries, resulting in small lesions. Often, these lesions can be difficult for Radiologists to spot, particularly if there are pre-existing small infarcts where it can be a laborious task to distinguish the old from the new. As part of MRI research investigating brain injury following cardiac surgery, we have been refining methods for digital registration and subtraction of MRI images to provide a 'difference map' making it easier to spot subtle changes in the brains of patients between scans. This research, conducted by Dr Emma Chung in partnership with Mark Horsfield (Xinapse) is soon to be published in the American Journal of Radiology (in press).

MRI studies of cerebral Autoregulation

Our team previously developed a novel method for mapping dynamic cerebral blood flow autoregulation to assess autoregulatory efficiency throughout the brain using MRI (published in PLoS ONE).

Models of cerebrovascular anatomy

Time-of-flight MR angiography techniques can be used to create a 3D reconstruction of the cerebral arteries for inclusion in computational models of cerebral blood flow and the development of realistic vascular phantoms. Our vascular phantoms are Ultrasound and MRI compatible and can be used for fluid dynamics experiments and testing novel methods of measuring of blood flow and brain tissue motion.   

 

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