Skin cancer margin detection using nanosensitive optical coherence tomography and a comparative study with confocal microscopy

Abstract

Excision biopsy and histology represent the gold standard for morphological investigation of the skin, in particular for cancer diagnostics. Nevertheless, a biopsy may alter the original morphology, usually requires several weeks for results, is non-repeatable on the same site and always requires an iatrogenic trauma. Hence, diagnosis and clinical management of diseases may be substantially improved by new non-invasive imaging techniques. Optical Coherence Tomography (OCT) is a non-invasive depth-resolved optical imaging modality based on low coherence interferometry that enables high-resolution, cross-sectional imaging in biological tissues and it can be used to obtain both structural and functional information. Beyond the resolution limit, it is not possible to detect structural and functional information using conventional OCT. In this paper, we present a recently developed technique, nanosensitive OCT (nsOCT), improved using broadband supercontinuum laser, and demonstrate nanoscale sensitivity to structural changes within ex vivo human skin tissue. The extended spectral bandwidth permitted access to a wider distribution of spatial frequencies and improved the dynamic range of the nsOCT. Firstly, we demonstrate numerical and experimental detection of a few nanometers structural difference using the nsOCT method from single B-scan images of phantoms with sub-micron periodic structures, acting like Bragg gratings, along the depth. Secondly, our study shows that nsOCT can distinguish nanoscale structural changes at the skin cancer margin from the healthy region in en face images at clinically relevant depths. Finally, we compare the nsOCT en face image with a high-resolution confocal microscopy image to confirm the structural differences between the healthy and lesional/cancerous regions, allowing the detection of the skin cancer margin.

Synthetic Fourier Domain Optical Coherence Tomography

“…For further visualization of the size of structures in an object in larger regions, where difference in periodicity cannot be seen, and ease of interpretation, a color map can be created. Each pixel in the color map is assigned its dominant spatial periodicity and the color of each pixel in the image corresponds to the particular dominant spatial periodicity assigned to that pixel, similar to nsOCT images, [16][17][18][19][20][21][22][23][24][25][26] as presented in Figure 4c. However, in contrast to nsOCT, synOCT facilitates imaging of the subwavelength structure within regions of interest in the depth (axial) direction, smaller than the resolution limit of the imaging system.…”

“…An approach to detect and visualize this information in an OCT image without resolving the depth structure spatially, nanosensitive OCT (nsOCT), has been published previously. [16][17][18][19][20][21][22][23][24][25][26] Here, we introduce and demonstrate a novel imaging approach which permits the estimation of the contribution of each detected axial spatial Fourier component of the object's structure in image formation. This can be achieved at any small areas within the image and provides quantitative access to subwavelength-sized structures in an object with nanosensitivity to structural changes.…”

“…An approach to detect and visualize this information in an OCT image without resolving the depth structure spatially, nanosensitive OCT (nsOCT), has been published previously. [ 16–26 ]…”

Super-resolution optical coherence tomography for biomedical applications

“…Where, n is the refractive index (~1.5 for biological tissue) and λ is the wavelength of the light source, Δλ is the bandwidth of the light source, λs and λl are the shortest and longest wavelengths of the light source spectrum, respectively [7]. The ns-OCT is capable of detecting high spatial frequencies which are lost during the process of reconstruction by Fourier transform in the conventional OCT.…”

“…The nanosensitive OCT assists in label-free, depth-resolved visualization of nanoscale structural changes in the spatial distribution, on a single OCT B-scan [3]. This approach has been used for detecting structural changes in time within milk and for detecting structural changes in nail fold by occluding the forearm, for the detection of tissue morphology using spatial frequency domain correlation mapping OCT [4], for the assessment of corneal wound healing [5], detection of alteration in the morphological structures during different stages of tumor progression by multifractal analysis [6], and for detecting the margin between healthy and cancerous/lesional ex vivo skin tissues [7].…”