High-speed multi-parametric photoacoustic microscopy of cerebral hemodynamic and metabolic responses to acute...

The ability of hemodilution to improve vascular circulatory impairment has been demonstrated. However, the effects of acute hemodilution on cerebral hemodynamics and oxygen metabolism have not been assessed at the microscopic level, due to technical limitations. To fill this void, we have developed a new, to the best of our knowledge, photoacoustic microscopy system, which enables high-speed imaging of blood hemoglobin concentration, oxygenation, flow, and oxygen metabolism in vivo. The system performance was examined in both phantoms and the awake mouse brain. This new technique enabled wide-field (4.5 × 3 mm²) multi-parametric imaging of the mouse cortex at 1 frame/min. Narrowing the field of view to 1.5 × 1.5 mm² allowed dynamic imaging of the cerebral hemodynamic and metabolic responses to acute hypervolemic hemodilution at 6 frames/min. Quantitative analysis of the hemodilution-induced cerebrovascular responses over time showed rapid increases in the vessel diameter (within 50-210 s) and blood flow (50-210 s), as well as decreases in the hemoglobin concentration (10-480 s) and metabolic rate of oxygen (20-480 s) after the acute hemodilution, followed by a gradual recovery to the baseline levels in 1440 s. Providing comprehensive insights into dynamic changes of the cerebrovascular structure and function in vivo, this technique opens new opportunities for mechanistic studies of acute brain diseases or responses to various stimuli.