Cancer Holography for Personalized Medicine

Abstract

Digital holography can measure the 3D physiology and motion of cancer cells, allowing identification of effective chemotherapies for patients.

A 3D reconstruction of a small living cancer tumor, acquired using low-coherence digital holography that performs laser ranging up to 1 mm deep into tissue, is color-coded for intracellular Doppler activity, displaying the high activity (red) of dividing cells and low activity (blue) in the low-oxygen core. Adapted from Z. Li et al., Appl. Opt. 60, A222 (2021)

Left: In digital holography, a pixel array (CCD) records the interference fringes of light scattered from a biological sample interfering with a reference wave (off-axis angle exaggerated) to form a speckle hologram. A phase image of the sample is numerically reconstructed from the hologram. Right: Quantitative phase imaging uses a galvo mirror to change the illumination angle on the sample to generate a series of holograms, allowing the numerical reconstruction of the 3D refractive-index variations in the sample (shown on the right for a live HeLa cell).

Optical schematic of the biodynamic imaging system in a Mach-Zehnder configuration. Light, backscattered from living tissue, is Fourier-transformed onto a pixel array, where it intersects a reference beam in an off-axis digital-holography configuration.

A digital hologram with holographic fringes modulating spatial speckle (left); its fast Fourier transform, showing the side-band images of the tissue section (center); and non-zero-path (NZP) subtraction, which removes the zero order.

Optical coherence image (OCI) of the midsection of a 600-μm-diameter tumor spheroid; a motility contrast image (MCI) representing the time-dependent speckle contrast; and volumetric MCI acquired by successive depth gates.