Neurovascular Coupling and Cerebral Perfusion Pressure- Biomarkers of Cerebral Health

 Under pressure, cerebral vessels in a healthy brain can alter their diameter to  maintain an adequate amount of blood flow and thereby a steady supply of oxygen  to the brain. This ability of the brain to compensate for perfusion pressure changes  is known as cerebral autoregulation. In several neuro-pathologies such as traumatic  brain injury, hydrocephalus, stroke, etc., this autoregulatory ability of the brain is  compromised. In such cases, a small change in pressure can cause drastic changes  in cerebral blood flow, leading to fatal secondary brain damages occurring from  ischemia (too little blood flow) or hyperemia (too much blood flow). Continuous  monitoring of cerebral health for timely diagnosis of such instances is essential to  improve patient outcome.  

This thesis proposes the use of neurovascular coupling as a non-invasive, bedside compatible biomarker for assessing cerebral perfusion pressures in relation to  autoregulatory health. Local neural activity and vascular tone are tightly coupled  in a healthy brain. This neuro-vascular coupling is essential to satiate oxidative metabolic needs from neuronal activity, regulate local tissue temperature, carry neuromodulators and post-synaptic wastes, etc. This coupling can be observed when  neural activity is evoked in a part of the brain using external stimuli causing in creases in local cerebral blood flow and volume in that region. It can also be studied  in a resting brain by mapping the coupling between local oxygen supply (cerebral  blood flow) and demand (cerebral metabolic rate of oxygen consumption), as well as  changes in resting neural signal power. However, in both instances, neurovascular coupling relies on adequate cerebral blood flow, which is impaired when autoregu lation breaks down.

 Here, through controlled pre-clinical experiments, I show that neurovascular  coupling– both stimulus- evoked, and at rest– can be used to assess cerebral health  at extreme cerebral perfusion pressures, linked to impaired autoregulation. Using  bedside compatible non-invasive measuring techniques such as diffuse optical spectroscopy and electroencephalography to assess neurovascular coupling I link changes  in neurovascular coupling to invasive measures of cerebral perfusion pressure. Finally, these techniques are used in a pediatric clinical setting to validate the clinical utility and translatability of neurovascular coupling as a biomarker for assessing  cerebral perfusion pressure and cerebral autoregulatory health.