Computational adaptive optics for broadband optical interferometric tomography of biological tissue

High-resolution real-time tomography of biological tissues is important for many areas of biological investigations and medical applications. Cellular level optical tomography, however, has been challenging because of the compromise between transverse imaging resolution and depth-of-field, the system and sample aberrations that may be present, and the low imaging sensitivity deep in scattering tissues. The use of computed optical imaging techniques has the potential to address several of these long-standing limitations and challenges. Two related techniques are interferometric synthetic aperture microscopy (ISAM) and computational adaptive optics (CAO). Through three-dimensional Fourierdomain resampling, in combination with high-speed OCT, ISAM can be used to achieve high-resolution in vivo tomography with enhanced depth sensitivity over a depth-of-field extended by more than an order-of-magnitude, in realtime. Subsequently, aberration correction with CAO can be performed in a tomogram, rather than to the optical beam of a broadband optical interferometry system. Based on principles of Fourier optics, aberration correction with CAO is performed on a virtual pupil using Zernike polynomials, offering the potential to augment or even replace the more complicated and expensive adaptive optics hardware with algorithms implemented on a standard desktop computer. Interferometric tomographic reconstructions are characterized with tissue phantoms containing sub-resolution scattering particles, and in both ex vivo and in vivo biological tissue. This review will collectively establish the foundation for high-speed volumetric cellular-level optical interferometric tomography in living tissues.