Optical Computational Imaging

The decoupling of axial and transverse resolution makes OCT possible to achieve rapid volumetric imaging with millimeter-scale imaging depth and micrometer-scale axial resolution by using a low numerical aperture (NA) optical system. The use of low-NA optics, however, comes at the expense of low transverse resolution. In many medical and surgical scenarios, however, higher transverse resolution for visualizing cellular features in vivo is desirable. Therefore, the long-standing trade-off between transverse resolution and depth-of-field (DOF) limits further development of OCT. As a broadband interferometry-based imaging technique, dispersion mismatch between the sample and reference paths negatively affects the axial resolution in OCT. Fully compensating for dispersion leads to the highest image quality, but this is often difficult to achieve in practice. Likewise, in some cases it is not desirable, or perhaps not possible, to achieve high-quality aberration-free imaging optics. In this case, aberrations can severely degrade the OCT image quality. Together, these limitations of dispersion mismatch, DOF, and optical aberration lead to restricted performance of an otherwise powerful imaging technology. One aim of the Biophotonics Imaging Laboratory is to develop noval optical computational imaging techniques to overcome these limitations.

Interferometric Synthetic Aperture Microscopy (ISAM)

State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light-sample interaction reveals that the Fourier space coverage is independent of depth. We have shown that by solving the inverse scattering problem for coherence microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. The entire illuminated volume has spatially-invariant resolution, thus eliminating the compromise between resolution and depth-of-field. This novel computational image-formation technique is capable of real-time imaging, and has the potential to broadly impact real-time 3-D microscopy and analysis in the fields of cell and tumor biology, as well as in clinical diagnosis where in vivo imaging is preferable to biopsy. We have analyzed and demonstrated this technique for rectangular Cartesian-coordinate imaging, for rotational catheter-based imaging, and for full-field imaging.

Renderings of 3-D OCT (left) and 3-D ISAM reconstruction (right) of a silicone tissue phantom containing 1 m TiO2 scatterers, demonstrating spatially invariant resolution.

En face images from human breast tissue. Images are shown for different depths. Histological sections (a,b) show comparable features with respect to the unprocessed interferometric data (c,d) and the ISAM reconstructions (e,f). The ISAM reconstructions resolve features in the tissue that are not decipherable from the unprocessed data. The green dashed arrow indicates the fast-scanning direction for the volumetric data acquisition.

Ralston TS, Marks DL, Carney PS, Boppart SA. Interferometric synthetic aperture microscopy.  Nature Physics, 3:129-134, 2007. n/a PDF


En face ISAM and OCT images from rat adipose tissue ex vivo showing that ISAM reconstruction of a plane far from focus provides comparable resolution to moving the focus to that plane. (a) En face OCT of a plane approximately 8 Rayleigh ranges above focus. (b) ISAM reconstruction of the same en face plane. (c) En face OCT with the focal plane moved to the plane of interest in (a). The field of view in each panel is 500 m by 500 m.

Ralston TS, Adie SG, Marks DL, Boppart SA, Carney PS. Cross-validation of interferometric synthetic aperture microscopy and optical coherence tomography.  Optics Letters, 35:1683-1685, 2010. n/a n/a



Real-time ISAM visualization of highly-scattering in vivo human skin from the wrist region acquired using a 0.1 NA OCT system, after placing the focus 1.2 mm beneath the skin surface. Cross-sectional results of (a) OCT and (b) ISAM. En face planes of (c) OCT and (d) ISAM at an optical depth of 520 µm into the tissue. (e) Variation of SNR with depth shows the improvement of ISAM, which was computed using the 20% (noise) and 90% (signal) quantiles of the intensity histograms. Compared to OCT, ISAM shows significant improvement over an extended depth range. CS, coverslip; GL, glycerol; SD, stratum disjunction; SC, stratum corneum; RD, reticular dermis; SF, subcutaneous fat. Scale bars represent 500 µm.

Ahmad A,  Shemonski ND, Adie  SG,  Kim HS,  Hwu WMW,  Carney PS, and  Boppart SA, "Real-time in vivo computed optical interferometric tomography," Nat. Photonics 7: 444–448, 2013.

PubMed Abstract




Ex vivo human breast tissue acquired from a NA 0.6 OCM system. En face planes of OCM at (a) the focal plane, a plane (b) 22 µm (5.8 Rayleigh lengths) and (c) 67 µm (17.6 Rayleigh lengths) above the focus plane. (d)-(f) ISAM reconstruction of the same en face planes of (a)-(c). The bright and highly scattering nuclei are indicated by the arrows. The scale bar in (a) denotes 50 µm, and applies to all images.

Liu YZ, Shemonski ND, Adie SG, Ahmad A, Bower AJ, Carney PS, and Boppart SA, "Computed optical interferometric tomography for high-speed volumetric cellular imaging," Biomed. Opt. Express 5(9), 2988–3000, 2014

PubMed Abstract



Simulated (left) and reconstructed (right) radial OCT catheter images of randomly distributed point scatterers.

Marks DL, Ralston TS, Carney PS, Boppart SA.  Inverse scattering for rotationally scanned optical coherence tomography.  J. Opt. Soc. Am. A, 23(10):2433-2439, 2006.

PubMed Abstract



Computational Adaptive Optics (CAO)

Aberration, which causes a deviation of an ideal wavefront, is an important issue affecting image quality in many imaging modalities. With increased NA for higher transverse resolution, the optical wavefront is more susceptible to being distorted by the imperfections of the imaging optics and the sample itself. As a result, the resolution may decrease, as well as the contrast and the signal-to-noise ratio. OCT/OCM also share this limitation are directly affected by aberrations in the system optics or the sample. Sophisticated optical designs can suppress the static system aberrations, but they are not versatile for complex biological tissues that introduce unique, often dynamically changing, sample aberrations. Hardware-based adaptive optics (HAO) physically sense and correct the aberrations for improving the signal strength and resolution. The systems, however, remain expensive and complex. In addition, the aberration compensation can only be valid for one isoplanatic patch during the imaging procedure, which extends the time of the imaging session for the application of large volumetric imaging. We have utilized the phase information of OCT/OCM to compensate the aberrations through post-processing.