Quantitative Optical Imaging of Oxygen in Brain Vasculature.

The intimate relationship between neuronal activity and cerebral oxygenation underpins fundamental brain functions like cognition, sensation, and motor control. Optical imaging offers a noninvasive approach to assess brain oxygenation and often serves as an indirect proxy for neuronal activity. However, deciphering neurovascular coupling─the intricate interplay between neuronal activity, blood flow, and oxygen delivery─necessitates independent, high spatial resolution, and high temporal resolution measurements of both microvasculature oxygenation and neuronal activation. This Perspective examines the established optical techniques employed for brain oxygen imaging, specifically functional near-infrared spectroscopy, photoacoustic imaging, optical coherence tomography, and two-photon phosphorescent lifetime microscopy, highlighting their fundamental principles, strengths, and limitations. Several other emerging optical techniques are also introduced. Finally, we discuss key technological challenges and future directions for quantitative optical oxygen imaging, paving the way for a deeper understanding of oxygen metabolism in the brain.