Improving multiple-scattering quantitative phase imaging using focus stepping

Quantitative phase imaging of biologically thick samples is challenging because multiple scattering events scramble the incoming and outgoing light fields, introducing an ill-posed inverse problem. While previous work on multiple-scattering inverse solvers for Optical and Intensity Diffraction Tomography (ODT/IDT) made progress in recovering the refractive index within highly scattering samples, it is still not clear what the best strategy is to image deep within such samples. One potential approach to constrain the set of possible solutions is to use Differential Phase Contrast (DPC) microscopy. DPC acquires images of the scattered light field from a low number of patterns at multiple discrete focus positions, in contrast to ODT/IDT approaches that acquire hundreds to thousands of patterns at one focus. To test if the additional prior information on the focal plane improves multiple scattering reconstruction of the refractive index (RI), we built a microscope with an LED illuminator capable of both DPC and IDT RI imaging modes. Using both DPC and IDT, we imaged 10-um polystyrene beads, C. elegans, and mouse intestinal tissue organoids. Here, we present ongoing work characterizing both weak-scattering and multiple-scattering inverse solvers on these datasets.