An innovative transparent cranial window based on skull optical clearing

Noninvasive optical methods for viewing the structural and functional organization of cortex have been playing important roles in brain research, which usually suffer from turbid skull. Various cranial window models based on surgical operation have been proposed, but have respective limitations. Here, an innovative transparent cranial window of mouse was established by topically treatment with a skull optical clearing solution (SOCS), rather than by craniotomy. Based on the experiment of optical clearing efficacy of skull in vitro , we found that the turbid skull became transparent within 25 min after application of SOCS. The USAF target is visible through the treated skull, and the calculated resolution can achieve 8.4 μm. After the in vivo skull was topically treated with SOCS, the cortical micro-vessels can be visible clearly. The quantitative analysis indicated that the minimum resolution diameter of micro-vessels in 14.4±0.8 μm through the transparent cranial window closed to that in 12.8±0.9 μm of the exposed cortical micro-vessels. Further, preliminary results from Laser Speckle Imaging demonstrated that there was no influence on cortical blood flow distribution of mouse after topically treatment with SOCS on skull. This transparent cranial window will provide a convenient model for cortex imaging in vivo , which is very significant for neuroscience research.