Collection of biopsies from the most pathologically advanced region is critical for histopathological assessment of potentially cancerous sites in the lung. However, current applications are limited in their ability to simultaneously image and collect samples in subsegmental airways. We demonstrate a suction-snare device guided with optical coherence tomography and autofluorescence imaging (OCT-AFI) to improve diagnostic yield in these airways. Biopsies collected in healthy ex-vivo porcine airways are shown to retain structural and functional information. Feasibility is demonstrated in an ex-vivo porcine model to assess tissue abnormality prior to biopsy collection.
Oral cancer management is challenging as many benign lesions present similarly to precancerous lesions; thus, non-invasive optical tools that can assess tissue status would provide utility in lesion monitoring and biopsy site selection. We hypothesize that there may be oral cancer-sensitive image biomarkers present in a novel image processing technique that interrogates angular scattering behaviour (multipath contrast imaging, MCI). This work retrospectively examines MCI of oral lesions imaged with a widefield endoscopic optical coherence tomography and autofluorescence imaging (OCT-AFI) device. Preliminary analysis shows subtle MCI intensity changes dysplasia and distinct visual changes in carcinoma when compared to contralateral.
We have previously demonstrated multimodal optical coherence tomography and autofluorescence imaging (OCT-AFI) in the distal airways of the lung. To combine the two modalities into a single-fiber endoscope, we use double-clad fibers, which causes additional blurred OCT images from the fibers' higher-order modes. Recently, we established multipath contrast imaging (MCI) which leverages these higher-order images to elucidate angular backscattering of tissue. MCI can be generated retroactively; we seek to re-evaluate images from our in vivo OCT-AFI lung cancer study. Early MCI results demonstrate high contrast in healthy tissue compared to blood, and for a histologically confirmed adenocarcinoma.
MOTIVATION: Biological samples are not always available to validate performance during development of optical imaging devices for in vivo detection of potentially malignant lesions. Thus, to provide readily available testing, there is a need for phantoms with optical response similar to that of target tissue.
OBJECTIVES: 1) Fabricate lung tissue phantoms that mimic structural and optical properties of central and segmental airways for 1310 ± 50 nm endoscopic OCT. 2) Simulate vascular flow to characterize angiography. 3) Produce a robust and cost-effective alternative to ex vivo tissue.
METHODS: An agar matrix is mixed with intralipid and coconut oil to achieve tissue-like absorption and scattering properties. A partitioned 3D printed mould is used to mimic airway geometry and embedded tubing is used to simulate vasculature. Fluid-flow is visualized with inter-A-line speckle decorrelation methods. Phantom optical performance is qualitatively and quantitatively compared against segmental airways in previous in vivo human studies using the same imaging system.
RESULTS: Images of common bronchial structures (eg: ducts, airway branches) reproduced in the phantoms qualitatively resemble similar structures in vivo (lung airway LB9) in OCT. Airway epithelial thickening indicative of dysplastic progression in vivo is re-created in the phantoms. Depth resolved attenuation coefficients are calculated and plotted for images collected on the same system, quantitatively characterizing replication. Live vasculature is mimicked using intralipid flow and visualized.
We hypothesize that there may be cancer-sensitive image biomarkers present in a novel image processing technique. We leverage the multipath artifacts derived from higher order modes that present in double clad fiber-based OCT systems, which are sensitive to scattering angle and as such may be sensitive to sub-resolution features such as nuclear density and size. This work explores multipath contrast in previously collected clinical imaging data; preliminary work has found that this technique can distinguish cancerous and non-cancerous fallopian tube specimens.
Multimodal imaging that includes optical coherence tomography and a secondary imaging modality in small single-channel endoscopes is often implemented using double-clad fiber (DCF). Unfortunately, the properties of DCF cladding modes generate multipath OCT artifacts degrading image quality. Curiously, the en face mean intensity projection of these multipath artifacts is a high quality image. The differential scattering of en face projections from the image and artifact could be used as an additional imaging modality, sensitive to sub-resolution features. Multipath artifacts are inherent to DCF-based OCT, meaning a wealth of previously acquired data could be explored using this technique.
Multimodal optical coherence tomography (OCT) can be implemented using double-clad fiber (DCF). A consequence of using DCF is the introduction of multipath artifacts which deteriorate the quality of OCT imaging. We demonstrate that a w-type DCF, characterized by a depressed cladding layer between the core and the multimode cladding, can eliminate OCT multipath artifacts. The modal contents of the fiber are determined from simulation and verified experimentally. A w-type fiber-based endoscope is used to generate co-registered OCT and autofluorescence imaging (AFI) with reduced artifacts. Results are compared with a DCF-based catheter.
Fluorophores associated with early development of cancer (FAD, NADH, collagen) and abnormalities in microvessel structure have been shown to correlate with oral cancer progression. Co-registered imaging approaches using optical coherence tomography (OCT) and fluorescence imaging techniques have demonstrated promise in assessing these biomarkers, but current endoscopic approaches are limited in specificity. We propose that a micromotor-based OCT angiography and fluorescence-lifetime imaging microscopy (FLIM) may provide a suitable biopsy guidance tool for oral cancer screening. We present initial work towards implementing these modalities with a micromotor catheter system, validated with phantoms. Performance is compared to our existing OCT-autofluorescence system.
Multipath artifacts in double clad fiber (DCF) based endoscopic optical coherence tomography (OCT) imaging systems are investigated and a novel mechanism for artifact generation is proposed. We present evidence that the characteristic image artifacts found in DCF OCT images are partially due to the existence of an index dip within the core of double clad optical fibers. This core dip is shown to affect the modal quality of the light propagating through the core of the DCF, causing additional peaks or ghost images to be generated within the point spread function of the OCT system. Through these investigations we hope to gain a better understanding of how modal artifacts degrade OCT image quality, allowing for the design of more ideal optical fibers which can restore the quality of the OCT imaging domain.
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