Noninvasive label-free imaging of microhemodynamics by optical-resolution photoacoustic microscopy

In vivo microcirculatory imaging facilitates the fundamental understanding of many major diseases. However, existing techniques generally require invasive procedures or exogenous contrast agents, which perturb the intrinsic physiology of the microcirculation. Here, we report on optical-resolution photoacoustic microscopy (OR-PAM) for noninvasive label-free microcirculatory imaging at cellular levels. For the first time, OR- PAM demonstrates quantification of hemoglobin concentration and oxygenation in single microvessels down to capillaries. Using this technique, we imaged several important yet elusive microhemodynamic activities-including vasomotion and vasodilation-in small animals in vivo. OR-PAM enables functional volumetric imaging of the intact microcirculation, thereby providing greatly improved accuracy and versatility for broad biological and clinical applications.