Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Ellis, Christopher G.

2nd Supervisor

Diop, Mamadou

Joint Supervisor

Abstract

The microcirculation is the site of oxygen exchange in the body, and little work has been done to determine if different microvascular beds respond similarly to a simultaneous vascular challenge. A hybrid microvascular monitoring device was developed that uses hyperspectral near-infrared spectroscopy and diffuse correlation spectroscopy to simultaneously monitor the brain and skeletal muscle. Experiments were conducted on Sprague Dawley rats (n=6, 156g±6.4g) to discern the effect that phenylephrine (0.1 mL bolus, 10 mg/kg) has on the mean arterial pressure (MAP), hemoglobin concentration, and blood flow in each microvasculature. Hemoglobin concentration increased by 2.1±0.2 mmol in the brain, and decreased by 2.5±1.0 mmol in skeletal muscle. Cerebral blood flow increased by 20.8±7.2% while muscular blood flow decreased by 7.5±1.5%. The response in the brain was dependent on the initial baseline MAP. This non-invasive method can be used to aid in clinical translation of findings in animal models.

Summary for Lay Audience

The microcirculation is the distal functioning unit of the cardiovascular system, where small blood vessels called capillaries are responsible for oxygen exchange. Red blood cells travel through capillaries and transport the protein responsible for carrying oxygen in the body, hemoglobin. The microcirculation regulates oxygen delivery, but the needs of the microcirculation changes from organ to organ; muscular blood flow can change nearly 100-fold, where cerebral blood flow must remain relatively constant.

Hemoglobin is a main light absorber in tissue, and we can take advantage of this light absorbing property to monitor changes in its characteristics non-invasively using light-based methods. This thesis accomplishes this by using two optical methods: hyperspectral near infrared spectroscopy (h-NIRS) and diffuse correlation spectroscopy (DCS). The h-NIRS device uses a white halogen lamp that was simultaneously directed at both the rat scalp to monitor the brain and the rat left hind limb to monitor the skeletal muscle. The DCS device uses a laser, which emits light at a single near-infrared wavelength, that was also simultaneously directed at both the brain and the skeletal muscle. Multiple injections of a vasoconstrictor, which constricts larger blood vessels like arteries and arterioles, were administered to increase blood pressure.

The purpose of this work was to develop a hybrid h-NIRS/DCS system that can simultaneously monitor the microcirculation in the brain and in skeletal muscle, and to demonstrate that this system can monitor changes in tissue dynamics. Comparing the results from the brain to those from skeletal muscle, we found that the response of the brain depended highly on the baseline blood pressure while the results for skeletal muscle do not. When blood pressure was low, there was an increase of blood to the brain and vice versa. This difference in response between the brain and skeletal muscle is likely due to strict regulation that occurs in the brain. This device could be used in diseases like diabetes and sepsis that have been shown to have microvascular deficits, as well as help bridge the gap between small animal disease models and what is seen in patients.

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