Comprehensive characterization of cerebrovascular oxygenation dynamics in awake mice using high-resolution photoacoustic imaging

Aims: Investigating cerebral oxygen saturation dynamics in awake animal models presents significant technical challenges. We introduce a novel approach utilizing high-resolution ultrasound photoacoustic (PA) imaging to monitor deep cerebrovascular oxygen saturation dynamics in awake mice.Methods: Swiss male and female mice (n=5-6) were immobilized using the Mobile HomeCage (Neurotar, Finland) floating platform. We used high-resolution ultrasound associated with PA imaging (VevoLAZR-X, Visualsonics) to track neurovascular oxygenation trajectories in awake mice in response to 2% isoflurane or dobutamine infusion (4.5 μg/g body weight).Results and Conclusions: High-resolution PA imaging successfully obtained deep brain oxygenation status in awake and intact-skull mice. Characterizing the hemodynamic responses of the mouse brain to isoflurane, we observed a rapid and transient increase in cerebrovascular sO2 (55.01 ± 1.10 % vs 60.15 ± 1.51 %, p<0.01) and increased hemoglobin in the brain cortex (24040 ± 2509 UA vs 25396 ± 2742 UA, p<0.05). Subsequently, challenging awake mice with the adrenergic agonist dobutamine revealed an increase in brain oxygen saturation correlated with heightened heart rate and cardiac output. Our study demonstrates the utility of high-resolution PA imaging for comprehensively characterizing cerebrovascular oxygenation dynamics in awake mice. These findings have implications for preclinical research and clinical practice, offering a non-invasive approach to investigate the effects of anesthesia and cardiovascular modulation on cerebral oxygen metabolism.