When
Where
Student: Akshita Sharma, Program in Applied Mathematics
Title: Theoretical Models for Control of Blood Flow and Oxygen Transport in Cerebral Microvascular Networks
Advisors: Tim Secomb, Physiology Dept.
Location: ENR2, Room N595
Abstract: Neurovascular coupling (NVC) is a complex process that links neuronal activity to blood flow and oxygen delivery in the cerebral cortex. Existing literature on NVC often independently considers vascular regulation, flow redistribution, and oxygen transport. In this dissertation, a mathematical modeling approach is taken to explore how these mechanisms are coordinated in the microcirculation to ensure adequate oxygen delivery in response to varying levels of neuronal activity. To examine how blood flow affects oxygen availability, a network-based model of blood flow and oxygen transport is applied to a realistic 3D microvascular network structure. The effects of single and multiple arteriolar constrictions on flow redistribution and consequently tissue oxygen perfusion are examined. A model of vascular diameter regulation is developed, based on known and hypothesized electrophysiological properties of the endothelial cells that line blood vessel walls, and on the active properties of vascular smooth muscle in the walls of arterioles. This model allows simulation of the causal sequence linking neuronal activity, conducted responses propagation, vascular regulation, flow redistribution, and oxygen transport. Finally, this model is used to predict how local changes in neuronal activity generate the BOLD fMRI signal, a widely used non-invasive method for studying brain activity. The results establish quantitative mechanistic explanations for observed features of the BOLD fMRI signal, including its temporal features and variation through the thickness of the brain cortex.