Flow-diffusion qBOLD MRI: a physiology-informed framework for simultaneous oxygen metabolism and perfusion mapping

Cerebral oxygen consumption measurement is paramount to our understanding of neuronal function, energy production and brain health. Current strategies for brain oxygenation mapping use MRI and the blood oxygen level dependent (BOLD) effect. However, few methods have been adopted in clinical practice, with the most successful ones relying on physiology-informed models of brain perfusion and oxygen delivery, with additional requirements of contrast-agent injection or calibration based on gas or respiratory challenges. In this study we propose to integrate a physiology-informed model of flow-diffusion of oxygen transport into a contrast-agent-free and gas/respiratory challenge-free quantitative BOLD framework (flow-diffusion qBOLD). The proposed method was characterised through simulations to identify and quantify sources of error when estimating oxygen consumption and blood perfusion parameters. Flow-diffusion qBOLD was then applied to MRI acquisitions in 12 healthy volunteers and results were compared to a breath-hold based calibrated BOLD (cBOLD) method. Lastly, a variance analysis of blood perfusion estimates further explored the model’s dependence on MRI measurements involved in flow-diffusion qBOLD and the potential effect of noise. Simulations uncovered sources of error yielding variations up to 5% on oxygen consumption estimates in physiological conditions. In vivo applications showed significant correlations between flow-diffusion qBOLD and cBOLD oxygen consumption estimates whilst identifying differential biases affecting the two methods. Overall we propose a well characterised physiology-informed model which provides a relevant alternative to calibrated protocols for studies in challenging clinical populations.