Noninvasive photoacoustic computed mesoscopy for longitudinal brain imaging

Photoacoustic imaging has become a powerful tool for visualizing the brain morphology, function, and metabolism. However, severe optical scattering and high-frequency acoustic attenuation within the brain degrade the performance of photoacoustic brain imaging. To address such limitation, we propose a line scanning–based photoacoustic computed mesoscopic (PACMes) approach for noninvasive, high-resolution, and longitudinal visualization of cerebral vasculature inside the intact mouse brain. This technique uses converging near-infrared (NIR) lines scanned at multiple angles for tight optical excitation; a low-frequency, full-ring ultrasound transducer array for high-sensitivity detection; and a compound reconstruction algorithm integrating filtered back-projection and optical localization of photoacoustic signals to recover the image. We perform long-term (>5 months), noninvasive imaging of the entire cortex of mice through the intact scalp and skull with a field of view of 13 millimeters and a spatial resolution of 33 micrometers. The results demonstrate the potential of PACMes for investigating brain function and disease.