Geometric transformation adaptive optics (GTAO) for volumetric deep brain imaging through gradient-index lenses

The advance of genetic function indicators has enabled the observation of neuronal activities at single-cell resolutions. A major challenge for the applications on mammalian brains is the limited optical access depth. Currently, the method of choice to access deep brain structures is to insert miniature optical components. Among these validated miniature optics, the gradient-index (GRIN) lens has been widely employed for its compactness and simplicity. However, due to strong fourth-order astigmatism, GRIN lenses suffer from a small imaging field of view, which severely limits the measurement throughput and success rate. To overcome these challenges, we developed geometric transformation adaptive optics (GTAO), which enables adaptable achromatic large-volume correction through GRIN lenses. We demonstrate its major advances through in vivo structural and functional imaging of mouse brains. The results suggest that GTAO can serve as a versatile solution to enable large-volume recording of deep brain structures and activities through GRIN lenses. The GRIN lenses widely used for deep brain functional imaging suffer from a small measurement field of view due to strong fourth-order astigmatism. Here the authors report Geometric Transformation Adaptive Optics (GTAO) that corrects field-dependent astigmatism and enables large-volume in vivo imaging of deep mouse brain through 0.5 mm GRIN lenses.