Live tissue viability and chemosensitivity assays using digital holographic motility contrast imaging

Holographic optical coherence imaging is an en face form of optical coherence tomography that uses low-coherence digital holography as a coherence gate to select light from a chosen depth inside scattering tissue. By acquiring successive holograms at a high camera frame rate at a fixed depth, dynamic speckle provides information concerning dynamic light scattering from intracellular motility. Motility contrast imaging (MCI) uses living motion as a label-free and functional biomarker. MCI provides a new form of viability assay and also is applicable for proliferation and cytotoxicity assays. The results presented here demonstrate that low-coherence digital holography can extract viability information from biologically relevant three-dimensional (3D) tissue based on multicellular tumor spheroids by moving beyond the format of two-dimensional cell culture used for conventional high-content analysis. This paper also demonstrates the use of MCI for chemosensitivity assays on tumor exgrafts of excised ovarian cancer tumors responding to standard-of-care cisplatin chemotherapy. This ex vivo application extends the applicability of MCI beyond 3D tissue culture grown in vitro.