The problem of optical scattering was long thought to fundamentally limit the depth at which light could be focused through turbid media such as fog or biological tissue. However, recent work in the field of wavefront shaping has demonstrated that by properly shaping the input light field, light can be noninvasively focused to desired locations deep inside scattering media. This has led to the development of several new techniques which have the potential to enhance the capabilities of existing optical tools in biomedicine. Unfortunately, extending these methods to living tissue has a number of challenges related to the requirements for noninvasive guidestar operation, speed, and focusing fidelity. Of existing wavefront shaping methods, time-reversed ultrasonically encoded (TRUE) focusing is well suited for applications in living tissue since it uses ultrasound as a guidestar which enables noninvasive operation and provides compatibility with optical phase conjugation for high-speed operation. In this paper, we will discuss the results of our recent work to apply TRUE focusing for optogenetic modulation, which enables enhanced optogenetic stimulation deep in tissue with a 4-fold spatial resolution improvement in 800-micron thick acute brain slices compared to conventional focusing, and summarize future directions to further extend the impact of wavefront shaping technologies in biomedicine.

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Joshua Brake, Haowen Ruan, J. Elliott Robinson, Yan Liu, Viviana Gradinaru, and Changhuei Yang, "Time-reversed ultrasonically encoded (TRUE) focusing for deep-tissue optogenetic modulation," Proc. SPIE 10502, Adaptive Optics and Wavefront Control for Biological Systems IV, 1050210 (Presented at SPIE BiOS: January 29, 2018; Published: 23 February 2018); https://doi.org/10.1117/12.2288331.