Ultrasonically Sculpted Virtual Optical Patterns for Imaging and Photostimulation in Brain Tissue

Optical imaging and photostimulation have been widely used in biological and medical applications. Penetration of light is limited by the scattering and absorption in tissue. Moreover, studying neural circuits using optogenetics to identify and isolate specific pathways and projections requires individual or simultaneous stimulation of multiple regions within the brain, which is not easily possible using existing optrodes. Here, we present a novel technique for guiding and steering of light deep in scattering tissue using non-invasive ultrasound. We show that a tunable virtual optical graded-index (GRIN) lens can be sculpted in tissue by using reconfigurable ultrasonic interference patterns, enabling bidirectional light delivery without implanting any physical light guide. The interaction of ultrasound and light is mediated through the tissue itself. We show that the ultrasonically sculpted tunable GRIN lenses can be used for light delivery as well as relaying images of the underlying structures within tissue, thus providing a noninvasive alternative for invasive implantable endoscopes. Using a custom-designed cylindrical ultrasonic array, complex patterns of light can be sculpted in the medium, including dipole and quadrupole shapes for multisite illumination. Finally, we demonstrate that this technique can be used to define spatial patterns of light to selectively target neurons in a mouse brain slice.