Computational augmentation of full-field optical coherence microscope for a single-shot volumetric cellular-resolution and millimeter-depth imaging

The optical coherence tomography microscope (OCM) is expected to provide a few millimeters of imaging depth. However, the high numerical aperture for cellular-level resolution results in only a-few-micrometers depth-of-focus (DOF). Although computational refocusing can sharpen the image, the confocality still limits the imaging depth. Additionally, the inevitable speckle significantly reduces the effective resolution. To overcome these limitations, we demonstrate a no-pinhole spatially coherent full-field OCM hardware with several holographic signal processing methods. The hardware provides the in-focus lateral resolution of 1.7 µm but its DOF is only 5.5 µm. However, the absence of the confocal pinhole and additional phase-only spatial frequency filtering enable post-acquisition extension of the imaging depth up to a few millimeters. Furthermore, newly introduced speckle-reduction method significantly improved the effective lateral resolution. The high-contrast and cellular-level volumetric imaging of cancer spheroids is demonstrated over the full depth of the sample (around 0.3 mm).