Label-free photoacoustic computed tomography of mouse cortical responses to retinal photostimulation using a pair-wise correlation map.

The lack of a non-invasive or minimally invasive imaging technique has long been a challenge to investigating brain activities in mice. Functional magnetic resonance imaging and the more recently developed diffuse optical imaging both suffer from limited spatial resolution. Photoacoustic (PA) imaging combines the sensitivity of optical excitation to hemodynamic changes and ultrasound detection's relatively high spatial resolution. In this study, we evaluated the feasibility of using a label-free, real-time PA computed tomography (PACT) system to measure visually evoked hemodynamic responses within the primary visual cortex (V1) in mice. Photostimulation of the retinas evoked significantly faster and stronger V1 responses in wild-type mice than in age-matched rod/cone-degenerate mice, consistent with known differences between rod/cone- vs. melanopsin-mediated photoreception. In conclusion, the PACT system in this study has sufficient sensitivity and spatial resolution to resolve visual cortical hemodynamics during retinal photostimulation, and PACT is a potential tool for investigating visually evoked brain activities in mouse models of retinal diseases.