Laser speckle imaging of brain blood flow through a transparent nanocrystalline yttria-stabilized-zirconia cranial implant

The laser speckle flowmetry methods based on laser speckle imaging (LSI) have attracted extensive attention recently because they can image brain blood flow with high spatiotemporal resolution. However, the poor transparency of the cranial bone limits the spatial resolution and the imaging depth. This problem has previously been addressed in animal studies by removing or thinning the skull to transparency. Nevertheless, a permanent and reliable solution has not yet been developed. Our study demonstrates a new method to address this challenge in biomedical imaging research, through the use of novel transparent cranial implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). By applying LSI to underlying brain in an acute murine model, we show that spatial resolution and quantitative accuracy of blood flow measurement are improved when imaging through transparent nc-YSZ implants relative to native cranium. As such, these results provide the initial evidence supporting the feasibility of nc-YSZ transparent cranial implant as a clinically-viable long-term optical access for LSI on a chronically-recurring basis, thereby suppressing the need for repeated craniotomies. Successful development of this method has the potential to advance the study of neuropathologies or novel neuro-procedures in animal models where measurement of cerebral blood flow is of interest, such as blood flow changes during stroke, changes in blood flow due to functional activation, and spreading depolarization and its role in brain injuries, pathophysiology of migraine, and subarachnoid hemorrhage.