Development of a photoacoustic microscopy technique to assess peritubular capillary function and oxygen metabolism in the mouse kidney

Microcirculatory changes and oxidative stress have long been associated with acute kidney injury. Despite substantial progress made by two-photon microscopy of microvascular responses to acute kidney injury in rodent models, little is known about the underlying changes in blood oxygen delivery and tissue oxygen metabolism. To fill this gap, we developed a label-free kidney imaging technique based on photoacoustic microscopy, which enables simultaneous quantification of hemoglobin concentration, oxygen saturation of hemoglobin, and blood flow in peritubular capillaries in vivo. Based on these microvascular parameters, microregional oxygen metabolism was quantified. We demonstrated the utility of this technique by studying kidney hemodynamic and oxygen-metabolic responses to acute kidney injury in mice subject to lipopolysaccharide-induced sepsis. Dynamic photoacoustic microscopy of the peritubular capillary function and tissue oxygen metabolism revealed that sepsis induced an acute and significant reduction in peritubular capillary oxygen saturation of hemoglobin, concomitant with a marked reduction in kidney ATP levels and contrasted with nominal changes in peritubular capillary flow and plasma creatinine. Thus, our technique opens new opportunities to study microvascular and metabolic dysfunction in acute and chronic kidney diseases.