Developing Wavefront Shaping Techniques for Focusing through Highly Dynamic Scattering Media

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit of ~1 mm in soft tissue. This greatly restricts the utility of optical diagnostic and therapeutic techniques, such as optogenetics, microsurgery, optical tweezing, and phototherapy of deep tissue, which require focused light in order to function. Wavefront shaping extends the depth at which optical focusing may be achieved by compensating for phase distortions induced by scattering, allowing for focusing through constructive interference. However, due to physiological motion, scattering of light in tissue is deterministic only within a brief speckle correlation time. In in vivo soft tissue, this speckle correlation is on the order of milliseconds. Because wavefront shaping relies on deterministic scattering in order to compensate for the resulting phase distortion, the wavefront must be optimized within this brief period. This presents a challenge as the speed of digital wavefront shaping has typically been limited by the relatively long time required to measure and display the optimal phase pattern due to the low speed of cameras, data transfer and processing, and spatial light modulators. In order to overcome these restrictions, wavefront shaping techniques which minimize the time required in measurement and display are therefore vital. In this dissertation, I will describe our efforts to improve the speed of wavefront shaping without sacrificing the performance of the systems. To this end, we have successfully developed several systems which are capable of full-phase wavefront shaping with latencies of 9 ms or less. In addition, we report an all-digital alignment compensation protocol, which may be used to obtain optimal alignment in digital optical phase conjugation systems, a key component when acquiring the best possible focusing performance