Full-field optical coherence tomography for the analysis of fresh unstained human lobectomy specimens

Abstract

Background:Full-field optical coherence tomography (FFOCT) is a real-time imaging technique that generates high-resolution three-dimensional tomographic images from unprocessed and unstained tissues. Lack of tissue processing and associated artifacts, along with the ability to generate large-field images quickly, warrants its exploration as an alternative diagnostic tool.Materials and Methods:One section each from the tumor and from adjacent non-neoplastic tissue was collected from 13 human lobectomy specimens. They were imaged fresh with FFOCT and then submitted for routine histopathology. Two blinded pathologists independently rendered diagnoses based on FFOCT images.Results:Normal lung architecture (alveoli, bronchi, pleura and blood vessels) was readily identified with FFOCT. Using FFOCT images alone, the study pathologists were able to correctly identify all tumor specimens and in many cases, the histological subtype of tumor (e.g., adenocarcinomas with various patterns). However, benign diagnosis was provided with high confidence in roughly half the tumor-free specimens (others were diagnosed as equivocal or false positive). Further analysis of these images revealed two major confounding features: (a) Extensive lung collapse and (b) presence of smoker's macrophages. On a closer inspection, however, the smoker's macrophages could often be identified as distinct from tumor cells based on their relative location in the alveoli, size and presence of anthracosis. We posit that greater pathologist experience, complemented with morphometric analysis and color-coding of image components, may help minimize the contribution of these confounders in the future.Conclusion:Our study provides evidence for the potential utility of FFOCT in identifying and differentiating lung tumors from non-neoplastic lung tissue. We foresee its potential as an adjunct to intra-surgical frozen section analysis for margin assessment, especially in limited lung resections.

Review of optical coherence tomography in oncology

“…The characteristic features associated with normal and neoplastic bronchial tissues 74 were also reported by the other peerreviewed works. [78][79][80] Furthermore, OCT identified in situ morphological changes associated with inflammatory infiltrates. 79 Inflamed tissue results in less well-defined OCT image features, where only the epithelium and lamina propria can be clearly delineated.…”

“…79 The potential utility of FF-OCT in identifying and differentiating lung tumors from nonneoplastic lung tissue was also demonstrated. 80 In addition to identifying lung tumor, various histological patterns of tumors could be identified in the FF-OCT images, especially for adenocarcinomas with various patterns.…”

Assessment of Sentinel Node Biopsies With Full-Field Optical Coherence Tomography

“…As compared to confocal systems, FFOCT further holds the advantage not to require lasers or fast scanning elements; the technique can be integrated in a simple setup. The FFOCT has already been evaluated in the pathology laboratory in various preclinical studies on human skin, 24,25 pulmonary, 26 urologic, 27 and gastrointestinal tissue, 28 retina and cornea, 29,30 and brain. 31 Recently, a preclinical study was performed on breast tissue samples 32 and achieved sensitivity of 92% and specificity of 77%.…”

Fourier spectrum analysis of full-field optical coherence tomography for tissue imaging

“…The values of these measures may be obtained by light-scattering spectroscopy-or imaging-based techniques. The highresolution optical sectioning capability of full-field optical coherence tomography (FFOCT) makes it possible to visualize the intact, in situ live tissue and locally quantify tissue structures and their changes [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. The advantage of visualizing intact live tissue over the sliced stained tissue observation in traditional microscopy is that more accurate information about tissue structure and the relationship between tissue elements may be provided because of the absence of freezing artefacts.…”

“…Here, the spatially incoherent illumination by using extended thermal light sources is to suppress the crosstalk between the neighbouring image points. In the following discussions, all the beam scanning-based OCT techniques will be referred to as scanning OCT. FFOCT has been used for measuring the brain refractive index in vivo [12], identifying cancer cells by measuring the refractive index distribution across a single live cell [13], obtaining sectional images of normal lung tissue and differentiating lung tumours from non-neoplastic lung tissue [14][15][16], producing en face tomographic images of both normal and cancerous liver [17], non-destructively evaluating film coatings applied to spherical pellet [18].…”