Quantification of the impact of variable mass transfer coefficients on oxygen transport in the brain

Oxygen is essential for brain function, as neurons have very high metabolic demands and even small changes in oxygen availability can affect their activity. The brain relies on a dense microcirculation network to deliver oxygen efficiently to all regions. Despite years of research, the understanding of oxygen transport in the brain remains limited. Computational modeling has become an important tool to explore these mechanisms and provide insights that experiments alone cannot deliver. A key element in oxygen transport is the exchange of oxygen between red blood cells (RBCs) and plasma, quantified by the mass transfer coefficient (MTC). The MTC determines the rate at which oxygen moves from RBCs to plasma, thereby influencing tissue oxygenation. While often assumed constant, recent studies showed that it varies with hematocrit and oxygen saturation. Accounting for this variability in models enhances their accuracy and better reflects the biological reality of oxygen transport. The aim of this project is to investigate the impact of MTCs on oxygen transport in the brain. Relationships between the MTC, hematocrit, and oxygen saturation were first derived from literature and then integrated into an existing computational model of cerebral oxygen transport. The numerical study followed a stepwise approach. Simplified test cases were first used to isolate the effect of variable MTCs, facilitating the evaluation of their direct impact on intravascular oxygen exchange. Subsequently, the model was applied to a realistic microvascular network containing approximately 950 vessels embedded in a cubic tissue domain, representing a small region of the somatosensory cortex of a mouse. This allowed assessment of how MTC variability shapes both vascular oxygen distribution and tissue oxygenation under more complex and physiologically realistic conditions. Results indicate that accounting for MTC variability improves the fidelity of oxygen transport predictions, particularly in regions with low hematocrit. Introducing variable MTCs increased the spatial heterogeneity of tissue oxygenation, leading to local differences of up to 20–25 mmHg and average variations of about 2–3 mmHg relative to the constant formulation. The proposed models produced consistent and physiologically grounded predictions, with Lücker providing the best trade-off between accuracy and computational cost. In conclusion, this project extends existing models by introducing a variable formulation of the MTC. The work highlights the importance of considering microvascular heterogeneity and shows its impact on predictions of oxygen dynamics. These findings improve the ability to model cerebral physiology and may also support the study of pathological conditions where oxygen supply is impaired.