Non-Invasive Assessment of Cerebrovascular Flow Impedance for Cerebral Autoregulation Monitoring

Maintaining appropriate cerebral perfusion is critical to the health and function of the human brain. To maintain a consistent cerebral blood flow (CBF), the body has a cerebral autoregulative (CA) mechanism which modulates cerebrovascular impedance (CVI) in response to slow baseline fluctuations in cerebral perfusion pressure (CPP). These changes in CVI are achieved through active vasoconstriction and vasodilation of the cerebral arterioles. However, in pathological disease states such as stroke or traumatic brain injury, this autoregulative mechanism can be disrupted, which in severe cases can lead to neurological damage due to ischemia or hemorrhage. Thus, measurement of CA function is invaluable for assessing cerebral health during pathological disease states where normal CBF is compromised. 

The aim of this thesis is to demonstrate a method to quantify CA function through assessments of vascular impedance. Measurements of vascular impedance have been attempted before, but the devices and techniques used have limited this assessment to only large arteries. This thesis demonstrates a novel design for a diffuse optical device that can resolve the pulsatile hemodynamics in the cerebral microvasculature based on diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). With this device, a method to measure the impedance changes using cardiac pulsations in the cerebral microvasculature is proposed. This device and method are validated using healthy human volunteers by resolving posture-driven impedance changes. 

To investigate the relationship between impedance and CA, non-human primate studies were performed to demonstrate impedance changes as a function of CPP. The results of these experiments showed that changes in impedance can reveal the upper and lower limits of autoregulation - key metrics of CA intactness. Moreover, this method was then translated to the clinical setting by applying impedance-based CA-based assessment to pediatric patients in an intensive care setting. 

Overall, the methods detailed in this thesis present a novel method for interrogating CA intactness. These methods may provide a way to assess cerebral health at the clinical bedside and will be beneficial in disease monitoring where CA may be impaired. Finally, the instrument design and methods presented in this work may enable deeper insight into information contained within the cardiac waveform, which can serve as a basis for other research opportunities.