Real-time tracking of brain oxygen gradients and blood flow during functional activation

Abstract

Significance: Cerebral metabolic rate of oxygen ( ${\mathrm{CMRO}}_2$ ) consumption is a key physiological variable that characterizes brain metabolism in a steady state and during functional activation.

Aim: We aim to develop a minimally invasive optical technique for real-time measurement of ${\mathrm{CMRO}}_2$ concurrently with cerebral blood flow (CBF).

Approach: We used a pair of macromolecular phosphorescent probes with nonoverlapping optical spectra, which were localized in the intra- and extravascular compartments of the brain tissue, thus providing a readout of oxygen gradients between these two compartments. In parallel, we measured CBF using laser speckle contrast imaging.

Results: The method enables computation and tracking of ${\mathrm{CMRO}}_2$ during functional activation with high temporal resolution ( $\sim 7\mathrm{Hz}$ ). In contrast to other approaches, our assessment of ${\mathrm{CMRO}}_2$ does not require measurements of CBF or hemoglobin oxygen saturation.

Conclusions: The independent records of intravascular and extravascular partial pressures of oxygen, CBF, and ${\mathrm{CMRO}}_2$ provide information about the physiological events that accompany neuronal activation, creating opportunities for dynamic quantification of brain metabolism.

Keywords: Oxyphor; blood flow; cerebral metabolic rate of oxygen; laser speckle contrast imaging; oxygen; phosphorescence quenching.