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 Professor TG Robinson, Dr MA Horsfield and Professor RB Panerai).