Multimodal Optical Imaging of Ex Vivo Fallopian Tubes to Distinguish Early and Occult Tubo-Ovarian Cancers.

There are currently no effective screening measures to detect early or occult tubo-ovarian cancers, resulting in late-stage detection and high mortality. This work explores whether an optical imaging catheter can detect early-stage tubo-ovarian cancers or precursor lesions where they originate in the fallopian tubes. This device collects co-registered optical coherence tomography (OCT) and autofluorescence imaging (AFI).

Imaging Biomarkers of Oral Dysplasia and Carcinoma Measured with In Vivo Endoscopic Optical Coherence Tomography.

Optical coherence tomography is a noninvasive imaging technique that provides three-dimensional visualization of subsurface tissue structures. OCT has been proposed and explored in the literature as a tool to assess oral cancer status, select biopsy sites, or identify surgical margins. Our endoscopic OCT device can generate widefield (centimeters long) imaging of lesions at any location in the oral cavity-but it is challenging for raters to quantitatively assess and score large volumes of data.

Three-Dimension Epithelial Segmentation in Optical Coherence Tomography of the Oral Cavity Using Deep Learning.

This paper aims to simplify the application of optical coherence tomography (OCT) for the examination of subsurface morphology in the oral cavity and reduce barriers towards the adoption of OCT as a biopsy guidance device. The aim of this work was to develop automated software tools for the simplified analysis of the large volume of data collected during OCT. Imaging and corresponding histopathology were acquired in-clinic using a wide-field endoscopic OCT system.

Tensor radiomics: paradigm for systematic incorporation of multi-flavoured radiomics features.

Background: Radiomics features hold significant value as quantitative imaging biomarkers for diagnosis, prognosis, and treatment response assessment. To generate radiomics features and ultimately develop signatures, various factors can be manipulated, including image discretization parameters (e.g.

Delineating spatial cell-cell interactions in the solid tumour microenvironment through the lens of highly multiplexed imaging.

The growth and metastasis of solid tumours is known to be facilitated by the tumour microenvironment (TME), which is composed of a highly diverse collection of cell types that interact and communicate with one another extensively. Many of these interactions involve the immune cell population within the TME, referred to as the tumour immune microenvironment (TIME). These non-cell autonomous interactions exert substantial influence over cell behaviour and contribute to the reprogramming of immune and stromal cells into numerous pro-tumourigenic phenotypes.

DNA Ploidy as a Potential Adjunct Prognostic Marker of Low-Risk Prostate Cancer Progression after Radical Prostatectomy.

Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population.

Prediction of Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer with High PD-L1 Expression Using Baseline CT Disease Quantification and Smoking Pack Years.

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress.

Automated PD-L1 Scoring for Non-Small Cell Lung Carcinoma Using Open-Source Software.

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to immunotherapy, but scoring of PD-L1 immunohistochemistry shows considerable interobserver variability. Automated methods may allow more consistent and expedient PD-L1 scoring. We aimed to assess the technical concordance of PD-L1 scores produced using free open source QuPath software with the manual scores of three pathologists.

An improved algorithm using a Health Canada-approved DNA-image cytometry system for non-invasive screening of high-grade oral lesions.

Background: DNA-image cytometry (DNA-ICM) is able to detect gross alterations of cellular DNA-content representing aneuploidy, a biomarker of malignancy. A Health Canada-approved DNA-ICM system, ClearCyte in combination with a cytopathologist's review, has demonstrated high sensitivity (89%) and specificity (97%) in identifying high-grade oral lesions. The study objective was to create an improved automated algorithm (iClearcyte) and test its robustness in differentiating high grade from benign reactive oral lesions without a cytopathologist's input.

Imaging intracellular motion with dynamic micro-optical coherence tomography.

This paper describes a new technology that uses 1-µm-resolution optical coherence tomography (µOCT) to obtain cross-sectional images of intracellular dynamics with dramatically enhanced image contrast. This so-called dynamic µOCT (d-µOCT) is accomplished by acquiring a time series of µOCT images and conducting power frequency analysis of the temporal fluctuations that arise from intracellular motion on a pixel-per-pixel basis. Here, we demonstrate d-µOCT imaging of freshly excised human esophageal and cervical biopsy samples.

Miniaturized multimodal multiphoton microscope for simultaneous two-photon and three-photon imaging with a dual-wavelength Er-doped fiber laser.

A multimodal multiphoton microscopy (MPM) is developed to acquire both two-photon microscopy (2PM) and three-photon microscopy (3PM) signals. A dual-wavelength Er-doped fiber laser is used as the light source, which provides the fundamental pulse at 1580 nm to excite third harmonic generation (THG) and the frequency-doubled pulse at 790 nm to excite intrinsic two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG). Due to their different contrast mechanisms, the TPEF, SHG, and THG images can acquire complementary information about tissues, including cells, collagen fibers, lipids, and interfaces, all label-free.

Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma.

Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity.

Submillimeter diameter rotary-pullback fiber-optic endoscope for narrowband red-green-blue reflectance, optical coherence tomography, and autofluorescence in vivo imaging.

A fiber-based endoscopic imaging system combining narrowband red-green-blue (RGB) reflectance with optical coherence tomography (OCT) and autofluorescence imaging (AFI) has been developed. The system uses a submillimeter diameter rotary-pullback double-clad fiber imaging catheter for sample illumination and detection. The imaging capabilities of each modality are presented and demonstrated with images of a multicolored card, fingerprints, and tongue mucosa.

Cervical cytology reproducibility and associated clinical and demographic factors.

Background: Although the Pap test has been the standard screening method for cervical precancer/cancer detection, it has been criticized for having a relatively low sensitivity and a low reproducibility between pathologists. There is limited knowledge about inter-rater agreement and what clinical and demographic factors are associated with disagreements between pathologists reading the same Pap smear.

Methods: This study aimed to assess inter- and intra- rater agreement of the Pap smear in 1619 cytologic slides with biopsy confirmation, using kappa statistics.

Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence.

Background: The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity.

Depth-multiplexed optical coherence tomography dual-beam manually-actuated distortion-corrected imaging (DMDI) with a micromotor catheter.

We present a new micromotor catheter implementation of dual-beam manually-actuated distortion-corrected imaging (DMDI). The new catheter called a depth-multiplexed dual-beam micromotor catheter, or mDBMC, maintains the primary advantage of unlimited field-of-view distortion-corrected imaging along the catheter axis. The mDBMC uses a polarization beam splitter and cube mirror to create two beams that scan circularly with approximately constant separation at the catheter surface.

Dual-beam manually actuated distortion-corrected imaging (DMDI): two dimensional scanning with a single-axis galvanometer.

We recently demonstrated a new two-dimensional imaging paradigm called dual-beam manually actuated distortion-corrected imaging (DMDI). This technique uses a single mechanical scanner and two spatially separated beams to determine relative sample velocity and simultaneously corrects image distortions due to manual actuation. DMDI was first demonstrated using a rotating dual-beam micromotor catheter.

Using quantitative tissue phenotype to assess the margins of surgical samples from a pan-Canadian surgery study.

Background: The purpose of this study was to use quantitative tissue phenotype (QTP) to assess the surgical margins to examine if a fluorescence visualization-guided surgical approach produces a shift in the surgical field by sparing normal tissue while catching high-risk tissue.

Methods: Using our QTP to calculate the degree of nuclear chromatin abnormalities, Nuclear Phenotypic Score (NPS), we analyzed 1290 biopsy specimens taken from surgical samples of 248 patients enrolled in the Efficacy of Optically-guided Surgery in the Management of Early-staged Oral Cancer (COOLS) trial. Multiple margin specimens were collected from each surgical specimen according to the presence of fluorescence visualization alterations and the distance to the surgical margins.

Correction of motion artifacts in endoscopic optical coherence tomography and autofluorescence images based on azimuthal en face image registration.

We present a method for the correction of motion artifacts present in two- and three-dimensional in vivo endoscopic images produced by rotary-pullback catheters. This method can correct for cardiac/breathing-based motion artifacts and catheter-based motion artifacts such as nonuniform rotational distortion (NURD). This method assumes that en face tissue imaging contains slowly varying structures that are roughly parallel to the pullback axis.

Quantification of large scale DNA organization for predicting prostate cancer recurrence.

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen-Thionin methodology, and scanned with a Pannoramic MIDI scanner.

Dual-beam manually-actuated distortion-corrected imaging (DMDI) with micromotor catheters.

We present a new paradigm for performing two-dimensional scanning called dual-beam manually-actuated distortion-corrected imaging (DMDI). DMDI operates by imaging the same object with two spatially-separated beams that are being mechanically scanned rapidly in one dimension with slower manual actuation along a second dimension. Registration of common features between the two imaging channels allows remapping of the images to correct for distortions due to manual actuation.

Dual-mode endomicroscopy for detection of epithelial dysplasia in the mouth: a descriptive pilot study.

Dual-mode endomicroscopy is a diagnostic tool for early cancer detection. It combines the high-resolution nuclear tissue contrast of fluorescence endomicroscopy with quantified depth-dependent epithelial backscattering as obtained by diffuse optical microscopy. In an in vivo pilot imaging study of 27 oral lesions from 21 patients, we demonstrate the complementary diagnostic value of both modalities and show correlations between grade of epithelial dysplasia and relative depth-dependent shifts in light backscattering.

Detection of precancerous lesions in the oral cavity using oblique polarized reflectance spectroscopy: a clinical feasibility study.

We developed a multifiber optical probe for oblique polarized reflectance spectroscopy (OPRS) in vivo and evaluated its performance in detection of dysplasia in the oral cavity. The probe design allows the implementation of a number of methods to enable depth resolved spectroscopic measurements including polarization gating, source–detector separation, and differential spectroscopy; this combination was evaluated in carrying out binary classification tasks between four major diagnostic categories: normal, benign, mild dysplasia (MD), and severe dysplasia (SD). Multifiber OPRS showed excellent performance in the discrimination of normal from benign, MD, SD, and MD plus SD yielding sensitivity/specificity values of 100%/93%, 96%/95%, 100%/98%, and 100%/100%, respectively.