Abstract

Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. Conventional intensity-based OCT provides depth-resolved imaging with a typical resolution and sensitivity to structural alterations of about 5–10 microns. It would be desirable for functional biological imaging to detect smaller features in tissues due to the nature of pathological processes. In this article, we perform the analysis of the spatial frequency content of the OCT signal based on scattering theory. We demonstrate that the OCT signal, even at limited spectral bandwidth, contains information about high spatial frequencies present in the object which relates to the small, sub-wavelength size structures. Experimental single frame imaging of phantoms with well-known sub-micron internal structures confirms the theory. Examples of visualization of the nanoscale structural changes within mesenchymal stem cells (MSC), which are invisible using conventional OCT, are also shown. Presented results provide a theoretical and experimental basis for the extraction of high spatial frequency information to substantially improve the sensitivity of OCT to structural alterations at clinically relevant depths.

Highlights

  • Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis

  • To confirm that information about small, sub-micron size structures in the object is present in Fourier domain OCT (FDOCT) signal and for further validation of the nano-sensitive OCT (nsOCT) approach, we imaged two samples from OptiGrate Corp., USA, which consist of axial periodic structure with different periods

  • B the peaks which correspond to structures with 431.6 nm and 441.7 nm periods are clearly seen. These results confirm that high spatial frequencies that correspond to small, submicron size structure are present in the OCT signal

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Summary

Introduction

Optical coherence tomography (OCT) is a rapidly evolving technology with a broad range of applications, including biomedical imaging and diagnosis. We analyze the spatial frequency content of the OCT signal based on general scattering ­theory[16] and show, theoretically and experimentally, that the information about high spatial frequencies of the object, that relates to its small, sub-wavelength size structure, is present in the OCT signal. This information is detected using FDOCT; the recorded spectral interference signal is a rescaled complex Fourier spectrum of the axial high spatial frequencies of the object. The visualization of the sub-wavelength structures, which would be invisible with conventional OCT, is demonstrated experimentally using phantoms with known internal structure, and on mesenchymal stem cells (MSCs)

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