Can OCT be sensitive to nanoscale structural alterations in biological tissue?

Abstract

Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distribution in tissue is quantified by its autocorrelation function modeled by the Whittle-Mateŕn functional family. By measuring the wavelengthdependent backscattering coefficient μ b (λ) and the scattering coefficient μ s , we introduce a technique called inverse spectroscopic OCT (ISOCT) to quantify the mass-density correlation function. We find that the length scale of sensitivity of ISOCT ranges from ~30 to ~450 nm. Although these subdiffractional length scales are below the spatial resolution of OCT and therefore not resolvable, they are nonetheless detectable. The subdiffractional sensitivity is validated by 1) numerical simulations; 2) tissue phantom studies; and 3) ex vivo colon tissue measurements cross-validated by scanning electron microscopy (SEM). Finally, the 3D imaging capability of ISOCT is demonstrated with ex vivo rat buccal and human colon samples.

Nano-sensitive optical coherence tomography

“…Recently the application of phase sensitive OCT to vibration measurements in the hearing organs 17 , including contribution of co-author of this paper 18 , and for investigation of human retina 19 at the nanoscale has been demonstrated. The ability of OCT to sense nanoscale structural alterations in weakly scattering media has been discussed 20 .…”

Nanosensitive optical coherence tomography for the study of changes in static and dynamic structures

“…Applica tion of the phase-sensitive OCT for measuring vibrations in the auditory organs [24,25] and studying the cornea [26] with nanoscale sensitivity has been demonstrated. A possibility of using OCT to register the changes in the nanostructured, weakly scattering media was discussed as well [27].…”

Spectroscopy of Scattered Light for the Characterization of Micro and Nanoscale Objects in Biology and Medicine

“…37,38 This approach employs a model of tissue that characterizes properties of the scattering volume. The scattering volume is assumed to be continuous position-dependent random media (not to be confused with time-dependent random media) that can be characterized by the shape of the correlation function, the correlation length, and the refractive index.…”