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 wavelength-dependent backscattering coefficient μb(λ) and the scattering coefficient μs, 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 sub-diffractional length scales are below the spatial resolution of OCT and therefore not resolvable, they are nonetheless detectable. The sub-diffractional 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.
Highlights
Studying nanoscale structural features within live intact biological tissue, while extremely challenging, has profound significance in understanding biological systems
Other in vivo optical techniques based on the light reflectance [14], such as polarized enhanced backscattering (EBS) [15] and polarization gated spectroscopy (PGS) [16], could be sensitive to nanoscale perturbation, while they are not able to provide a geometrical image of tissue
We have demonstrated results indicating that our spectroscopic analysis by inverse spectroscopic optical coherence tomography (ISOCT) is sensitive to R.I., and the mass-density correlation function, at length scales from ~35 to ~450nm
Summary
Studying nanoscale structural features within live intact biological tissue, while extremely challenging, has profound significance in understanding biological systems. During the last three decades, numerous advanced optical techniques have been demonstrated to break the diffraction limit and visualize sub-diffractional structures [6,7,8,9,10,11,12,13] Such optics or instrumentation are only applicable to individual cells or thinly sliced tissue rather than intact, in situ tissue. We have demonstrated a technique called inverse spectroscopic optical coherence tomography (ISOCT) to quantify the tissue R.I. correlation function [29]. ISOCT measures the optical properties, including the backscattering coefficient spectrum μb(λ) and the reflection ratio α (defined as the ratio of backscattering and scattering coefficients, α = μb/ μs), to much more accurately deduce the R.I. correlation function [29]. Another advantage is that the 3D capability of OCT provides guidance to investigate a particular region of interest
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