High-resolution optical longitudinal cortical imaging usually uses cranial window, which involves removing a skull portion and sealing the exposed brain area with a transparent cover glass, allowing ballistic photons to reach the cortex with minimal disturbance of the brain function. It enables obtaining high-resolution brain images in extended periods of time for long-term neuronal activity studies using confocal and two-photon microscopies. Photoacoustic microscopy (PAM), as the only imaging method that directly measure absorption contrast, is a complementary functional imaging method to provide absorption related brain information, such as total concentration of hemoglobin and oxygen saturation of hemoglobin. However, the use of traditional piezoelectric transducers (PZT) to collect ultrasound signal greatly limits the versatility of PAM. Though highly sensitive, PZT transducers are usually bulky and optically opaque. It blocks the light and is hard to be inserted into the limited distance between the optical objective and imaging sample, which are normally less than one millimeter when using a high- numerical aperture (NA) objective to achieve submicron resolution.
Here, we developed a simple and cost-efficient soft nanoimprint lithography (NIL) process to fabricate fully embedded micro-ring resonator ultrasound detectors on optically transparent substrates, and integrated the detector onto a cranial window, making cranial window itself an ultrasonic detector. We implanted this functional cranial window on mouse head and achieved longitudinal monitoring of cortex vasculature using PAM. Our low-cost, disposable, and optically transparent detector may potentially reshape the longitudinal functional brain imaging using PAM in small animals.
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