Seeing Through the Fog: Using Scattered Light to Peer Deeper into Biological Tissue

Abstract

Optical scattering is a fundamental problem in biomedical optics and limits most optical techniques to shallow operating depths less than 1 millimeter. However, although the scattering behavior of tissue scrambles the information it contains, it does not destroy it. Therefore, if you can unscramble the scattered light, it increases the accessible imaging depths up the absorption limit of light (several centimeters deep). One such way to beat optical scattering is using wavefront shaping. Borrowing ideas from adaptive optics in astronomy and phased arrays in radar and ultrasonic imaging, the basic concept of wavefront shaping is to control the phase and amplitude of the light field in order to harness scattered light. Using wavefront shaping techniques, scattered light can be used to form focal spots or transmit information through or inside optically scattering media. Furthermore, even without correcting for scattering directly by shaping the input light field, the properties of the scattered light can be analyzed to recover information about the structure and dynamic properties of a sample using methods from diffuse optics. The main contributions of this thesis are along these two lines of research: moving wavefront shaping toward more practical applications and developing new techniques to recover useful physiological information from scattered light. This is developed through three main projects: (1) an investigation of how dynamic samples impact the scattering process and the practical implications of these dynamics on wavefront shaping systems, (2) the development of a wavefront shaping system combining light and ultrasound to focus light inside acute brain slices to improve light delivery for optogenetics, (3) a novel method to sensitively detect the dynamics of scattered light and use it to tease out information about the flow of blood within the tissue sample of interest.