Electronic Thesis and Dissertation Repository

Thesis Format



Master of Science


Medical Biophysics


StLawrence, Keith

2nd Supervisor

Diop, Mamadou



Cerebral blood flow (CBF) and oxygen delivery are tightly controlled to meet neuronal energy demands; however, studying dynamic neurovascular coupling in the human brain is challenging due to the lack of methods that can measure rapid changes in CBF and tissue oxygenation. This report presents an in-house-developed hybrid time-resolved near-infrared spectroscopy/diffuse correlation spectroscopy (TR-NIRS/DCS) device and its use to track dynamic CBF and tissue oxygen saturation (StO2) responses simultaneously with sub-second resolution following a vasodilatory stimulus (i.e., a hypercapnic challenge).

Cerebrovascular reactivity (CVR) experiments were performed on 10 healthy participants (mean age: 27 years) using a computer-controlled gas delivery system to manipulate breath-to-breath inspired CO2 levels. TR-NIRS and DCS data were acquired continuously at a sampling frequency of 3 Hz to capture dynamic CBF and oxygenation responses. CVR measurements derived from oxyhemoglobin and deoxyhemoglobin concentrations were 3.4 ± 2.6 and 3.0 ± 1.9 %/mmHg, respectively. Their dynamic component, a fitted exponential coefficient that defines the speed of the response as per the hemodynamic response function, was estimated to be 32 ± 16 and 33 ± 28 seconds. The corresponding CVR value and dynamic component derived from CBF was 3.5 ± 3.6 %/mmHg and 33 ± 18 seconds. These experiments demonstrated that the optical system had sufficient temporal resolution to capture the dynamics of the oxygenation and CBF responses to a vasodilatory stimulus.

Summary for Lay Audience

The brain needs a constant flow of blood and oxygen to keep working. The organ’s ability to react to changes and provide more blood and higher oxygen levels is called the cerebrovascular reactivity or CVR. This reactivity value is a good sign of how healthy the brain is, as lower CVR has been measured in patients with diseases such as Alzheimer's. Conventionally, CVR is determined by letting a subject breath carbon dioxide as this increases the width of the vessels in their brain, and measuring the resulting increase in blood flow and consequently, higher oxygen levels. Researchers have several tools at their disposal to measure this value such as magnetic resonance imaging, ultrasound, and positron emission tomography. However, newer laser technologies are able to make the same measurements with several key benefits. These techniques are better as they do not require injections, take up less space, are relatively inexpensive and make very quick measurements. This last point is important as fast measurements allow researchers to analyze the change in blood flow and oxygen as it is happening rather than focusing on just the total increase of both factors.

This project involves two laser technologies which were modified and combined to produce a hybrid system that could measure both oxygen content and blood flow simultaneously in the brain. Such a system has never been developed before for use on adults. CVR was measured from 10 participants as well as values that define the speed of their response to the inhaled carbon dioxide. These values matched what has been found in previous studies using more expensive devices. Scalp contamination was also investigated with depth-sensitive techniques applied to achieve more signal from the brain.

Overall, this study shows that CVR can be measured by optical systems, specifically these two simultaneously. Such a unified hybrid system has never been applied to adults, which opens up many possible applications. One immediate application could be to focus on the aging populating, measuring CVR in elderly subjects to find signs of early stage Alzheimer's disease. This could open the doors to a new diagnostic system.