Abstract
Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals. However, an active CCW capable of sensing the concealed in vivo environment while simultaneously providing longitudinal optical access to the brain is not currently available. Here we report a disposable ultrasound-sensing CCW (usCCW) featuring an integrated transparent nanophotonic ultrasonic detector fabricated using soft nanoimprint lithography process. We optimize the sensor design and the associated fabrication process to significantly improve detection sensitivity and reliability, which are critical for the intend longitudinal in vivo investigations. Surgically implanting the usCCW on the skull creates a self-contained environment, maintaining optical access while eliminating the need for external ultrasound coupling medium for photoacoustic imaging. Using this usCCW, we demonstrate photoacoustic microscopy of cortical vascular network in live mice over 28 days. This work establishes the foundation for integrating photoacoustic imaging with modern brain research.
Highlights
Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals
To demonstrate that active CCW allows additional measurement capability other than optical access, we show that ultrasound-sensing CCW (usCCW) enables longitudinal photoacoustic microscopy (PAM) cortical imaging (Fig. 4a) for nearly one a d e
While our usCCW is compatible with both configurations, we find that thinned-skull configuration results in weaker ultrasound signal (Supplementary Note 6 and Supplementary Fig. 7) due to higher acoustic attenuation caused by the residual bone structure
Summary
Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals. Implanting the usCCW on the skull creates a self-contained environment, maintaining optical access while eliminating the need for external ultrasound coupling medium for photoacoustic imaging. Using this usCCW, we demonstrate photoacoustic microscopy of cortical vascular network in live mice over 28 days. Researchers incorporated CCW with optogenetic tools to achieve selective optical stimulation and suppression of neuron activities in live animals[8] Despite these successes, the surgical implantation of CCW precludes direct physical access to the brain other than optical access. Transforming CCW into an active sensing device would provide a highly desirable solution for conducting additional long-term studies, while still preventing contaminating the brain and keeping the animal in a healthy condition Such a device is not currently available. The functions of the active usCCW is validated experimentally through longitudinal photoacoustic microscopy (PAM) imaging of cortical vasculatures in live mice over 28 days
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