Project Summary The objective of this study is to investigate an optically computed compressive optical coherence tomography (OCC- OCT) technology for ultra-high speed phase-resolved dynamic imaging. Optical coherence tomography (OCT) is a cross- sectional imaging modality based on low coherence light interferometry. OCT has been used to image mechanical motion at cellular and tissue level for various biomedical applications. However, the state-of-the-art OCT technology does not provide sufficiently high spatiotemporal resolution to image en face plane or other arbitrary 2D planes, which limits its capability to study many biologically significant dynamic events. Here we propose an OCC-OCT technology that tracks subtle motion within an extended field of view, by utilizing an innovative optical computation strategy for snap shot phase resolved imaging. To achieve depth resolution and phase sensitivity, the OCC-OCT system uses a hardware optical computation module to calculate the inner product between interferometric spectra and a chosen Fourier basis function. In addition, the output of the optical computation module is hardware compressed within the framework of compressive sensing. A digital micromirror device (DMD) imposes a set of random spatial masks during the camera’s exposure time. Given the known random pattern used for modulation, high speed scenes are reconstructed within the framework of compressive sensing by promoting sparsity. With unprecedented spatiotemporal accuracy, OCC-OCT enables quantitative analysis of dynamic phenomenon (A(r, t)) on its temporal evolution (∂A(r, t)/∂t) and spatial propagation (∇A(r, t)), which is crucial to establish mathematical models to reveal the underlying mechanisms of dynamic events in biological systems. In this project, OCC-OCT system will be developed and evaluated. The imaging system will be used to perform spatially resolved dynamic imaging and 3D cell tracking. OCC-OCT is anticipated to advance many fields of biophotonics, including optical coherence elastography, optical coherence angiography, optogenetics and neural activity imaging, 3D tracking of unlabeled cells, etc.