Two-photon microscopy measurement of cerebral metabolic rate of oxygen using periarteriolar oxygen concentration gradients

Abstract

© 2016 Society of Photo-Optical Instrumentation Engineers (SPIE). The cerebral metabolic rate of oxygen (CMRO2) is an essential parameter for evaluating brain function and pathophysiology. However, the currently available approaches for quantifying CMRO2 rely on complex multimodal imaging and mathematical modeling. Here, we introduce a method that allows estimation of CMRO2 based on a single measurement modality-two-photon imaging of the partial pressure of oxygen (PO2) in cortical tissue. We employed two-photon phosphorescence lifetime microscopy (2PLM) and the oxygen-sensitive nanoprobe PtP-C343 to map the tissue PO2 distribution around cortical penetrating arterioles. CMRO2 is subsequently estimated by fitting the changes of tissue PO2 around arterioles with the Krogh cylinder model of oxygen diffusion. We measured the baseline CMRO2 in anesthetized rats and modulated tissue PO2 levels by manipulating the depth of anesthesia. This method provides CMRO2 measurements localized within ∼200μm and it may provide oxygen consumption measurements in individual cortical layers or within confined cortical regions, such as in ischemic penumbra and the foci of functional activation.