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.
Current cervical screening techniques are fairly effective at assessing the ectocervical surface, but they are limited in their capacity to assess the endocervical canal. There is a need for tools that examine the endocervical canal for cancerous or pre-cancerous lesions. This pilot study explores whether an endoscopic imaging approach combining structural and functional imaging techniques (optical coherence tomography (OCT) and autofluorescence imaging (AFI) respectively) can visualize cancerous or pre-cancerous changes in the endocervical canal. We present findings from an on-going in vivo imaging study including sample cases demonstrating precancers and cancers and preliminary features of interest.
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.
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.
The most prevalent ovarian cancers, high-grade serous carcinomas (HGSCs), begin as lesions in the fallopian tubes. There is a need for tools that examine the fallopian tubes for early-stage ovarian cancers. We hypothesize an endoscopic imaging approach combining structural and functional imaging techniques (optical coherence tomography (OCT) and autofluorescence imaging (AFI) respectively) will be able to visualize cancerous or pre-cancerous changes in the fallopian tubes for early ovarian cancer detection. We present findings from an on-going ex vivo imaging study of fallopian tubes including sample cases demonstrating various cancers and preliminary features of interest.
Significance: Chronic lung allograft dysfunction (CLAD) is the leading cause of death in transplant patients who survive past the first year post-transplant. Current diagnosis is based on sustained decline in lung function; there is a need for tools that can identify CLAD onset.
Aim: Endoscopic optical coherence tomography (OCT) can visualize structural changes in the small airways, which are of interest in CLAD progression. We aim to identify OCT features in the small airways of lung allografts that correlate with CLAD status.
Approach: Imaging was conducted with an endoscopic rotary pullback OCT catheter during routine bronchoscopy procedures (n = 54), collecting volumetric scans of three segmental airways per patient. Six features of interest were identified, and four blinded raters scored the dataset on the presence and intensity of each feature.
Results: Airway dilation (AD) was the only feature found to significantly (p < 0.003) correlate with CLAD diagnosis (R = 0.40 to 0.61). AD could also be fairly consistently scored between raters (κinter-rater = 0.48, κintra-rater = 0.64). There is a stronger relationship between AD and the combined obstructive and restrictive (BOS + RAS) phenotypes than the obstructive-only (BOS) phenotype for two raters (R = 0.92 , 0.94).
Conclusions: OCT examination of small AD shows potential as a diagnostic indicator for CLAD and CLAD phenotype and merits further exploration.
Cervical cancer continues to be among the most frequently diagnosed and fatal cancers among women, ranking fourth in both categories globally in 2018. Detecting and treating early signs of cervical cancer drastically improves patient survivability. We will present images of the inner endocervical canal and the ectocervix taken by a fiber-based imaging system capable of co-registered Optical Coherence Tomography (OCT) and Autofluorescence Imaging (AFI). The rotary-pullback double clad fiber (DCF) imaging catheter captures 3D volumetric OCT scans and 2D AFI surface maps from within the endocervix. Images are obtained from patients undergoing colposcopy-guided biopsies or Loop Electrosurgical Excision Procedure (LEEP).
Ovarian cancer is one of the most lethal gynecological conditions in the developed world. Current screening methods have only made marginal differences in overall survival over the past 30 years. The deficit of early-stage detection methods is a critical factor in the mortality associated with this disease. Recent evidence has shown that the fallopian tubes are a critical site in carcinogenesis of ovarian cancers. We present the first endoscopic co-registered OCT-AFI imaging of ex vivo fallopian tubes. This work aims to evaluate the potential of OCT-AFI to identify pre-cancerous lesions in the fallopian tubes. The BC Cancer Research Centre’s Optical Imaging Lab has developed a multimodal imaging system and catheter which enables both optical coherence tomography (OCT) and autofluorescence imaging (AFI). The imaging probe consists of a dual-clad fiber optical core inside a 0.9mm diameter sterile sheath. This system allows for resolutions of 20-30μm and imaging depths of up to 1.5mm. Samples are collected from patients consented through the OVCARE Gynecological Cancer Tissue Bank banking protocol. Volumetric OCT-AFI images are acquired for the entire catheterizable length of the sample at pullback speeds of 1mm/s. After imaging, histology is conducted according to the “sectioning and extensively examining the fimbriated end” protocol to serve as a gold standard. We present methods for obtaining scans of the ex vivo fallopian tubes, sample cases correlated with histology, and our preliminary results. As of January 2020, we have imaged 21 patients and 27 fallopian tubes including 6 cancerous specimens.
This study explores endobronchial optical coherence tomography (OCT) imaging of lung transplant patients with chronic lung allograft dysfunction (CLAD). Optical coherence tomography (OCT), the optical analog of ultrasonography with superior resolution (10μm) but shallow (2mm) penetration, allows for the visualization of the early structural changes in the small airways, which is of interest in CLAD progression. Imaging was conducted with a catheter-based rotary OCT probe during routine bronchoscopy procedures, resulting in three-dimension pullbacks of three subsegmental airways per patient (n=9). A scoring rubric for visualized features of interest was used to quantify characteristics of the image set: loss of alveolar visualization, emphysema-like alveolar enlargement, alveolar hyperinflation, airway dilation, excessive mucous, excessive duct-like structures, and an unidentified structure. Four raters, blinded to clinical status, scored the set. Statistical analysis including Pearson correlation coefficients (R), Fleiss’ Kappa (κ) were used on this score set to assess preliminary potential of these features. 3/9 patients met the diagnostic criteria for both obstructive (BOS) and restrictive (RAS) phenotypes of CLAD and 6/9 for solely the obstructive phenotype. The airway dilation feature was found to be significantly associated (p<0.05) with the BOS+RAS diagnosis for three raters (R=0.72-0.94), with fairly consistent rater reliability (κinterrater = 0.25, κintrarater = 0.59). No OCT features were significantly correlated with infection status. Small airway dilation, as measured through catheterized OCT imaging, shows potential for use in detection of CLAD and distinguishing between CLAD phenotypes.
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