Imaging Unit

Vancouver, Canada

Imaging Unit

Vancouver, Canada

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MacAulay C.,Imaging Unit | Follen M.,Texas Tech University Health Sciences Center | Guillaud M.,Imaging Unit
Biomedical Optics Express | Year: 2014

We use an extensive set of quantitative histopathology data to construct realistic three-dimensional models of normal and dysplastic cervical cell nuclei at different epithelial depths. We then employ the finitedifference time-domain method to numerically simulate the light scattering response of these representative models as a function of the polar and azimuthal scattering angles. The results indicate that intensity and shape metrics computed from two-dimensional scattering patterns can be used to distinguish between different diagnostic categories. Our numerical study also suggests that different epithelial layers and angular ranges need to be considered separately to fully exploit the diagnostic potential of twodimensional light scattering measurements. © 2014 Optical Society of America.


MacAulay C.,Imaging Unit | Follen M.,Texas Tech University Health Sciences Center | Guillaud M.,Imaging Unit
Optics InfoBase Conference Papers | Year: 2013

Dysplastic progression is known to be associated with changes in morphology and internal structure of cells. A detailed assessment of the influence of these changes on cellular scattering response is needed to develop and optimize optical diagnostic techniques. In this study, we first analyzed a set of quantitative histopathologic images from cervical biopsies and we obtained detailed information on morphometric and photometric features of segmented epithelial cell nuclei. Morphometric parameters included average size and eccentricity of the best-fit ellipse. Photometric parameters included optical density measures that can be related to dielectric properties and texture characteristics of the nuclei. These features enabled us to construct realistic three-dimensional computational models of basal, parabasal, intermediate, and superficial cell nuclei that were representative of four diagnostic categories, namely normal (or negative for dysplasia), mild dysplasia, moderate dysplasia, and severe dysplasia or carcinoma in situ. We then employed the finite-difference time-domain method, a popular numerical tool in electromagnetics, to compute the angle-resolved light scattering properties of these representative models. Results indicated that a high degree of variability can characterize a given diagnostic category, but scattering from moderately and severely dysplastic or cancerous nuclei was generally observed to be stronger compared to scattering from normal and mildly dysplastic nuclei. Simulation results also pointed to significant intensity level variations among different epithelial depths. This suggests that intensity changes associated with dysplastic progression need to be analyzed in a depth-dependent manner. © 2013 OSA-SPIE.


Macaulay C.,Imaging Unit | Follen M.,Texas Tech University Health Sciences Center | Guillaud M.,Imaging Unit
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2014

Dysplastic progression in epithelial tissues is linked to changes in morphology and internal structure of cell nuclei. These changes lead to alterations in nuclear light scattering profiles that can potentially be monitored for diagnostic purposes. Numerical tools allow for simulation of complex nuclear models and are particularly useful for quantifying the optical response of cell nuclei as dysplasia progresses. In this study, we first analyze a set of quantitative histopathology images from twenty cervical biopsy sections stained with Feulgen-thionin. Since Feulgen-thionin is stoichiometric for DNA, the images enable us to obtain detailed information on size, shape, and chromatin content of all the segmented nuclei. We use this extensive data set to construct realistic three-dimensional computational models of cervical cell nuclei that are representative of four diagnostic categories, namely normal or negative for dysplasia, mild dysplasia, moderate dysplasia, and severe dysplasia or carcinoma in situ (CIS). We then carry out finite-difference time-domain simulations to compute the light scattering response of the constructed models as a function of the polar scattering angle and the azimuthal scattering angle. The results show that these two-dimensional scattering patterns exhibit characteristic intensity ridges that change form with progression of dysplasia; pattern processing reveals that Haralick features can be used to distinguish moderately and severely dysplastic or CIS nuclei from normal and mildly dysplastic nuclei. Our numerical study also suggests that different angular ranges need to be considered separately to fully exploit the diagnostic potential of two-dimensional light scattering measurements. © 2014 SPIE.


PubMed | Imaging Unit and Texas Tech University Health Sciences Center
Type: Journal Article | Journal: Biomedical optics express | Year: 2014

We use an extensive set of quantitative histopathology data to construct realistic three-dimensional models of normal and dysplastic cervical cell nuclei at different epithelial depths. We then employ the finite-difference time-domain method to numerically simulate the light scattering response of these representative models as a function of the polar and azimuthal scattering angles. The results indicate that intensity and shape metrics computed from two-dimensional scattering patterns can be used to distinguish between different diagnostic categories. Our numerical study also suggests that different epithelial layers and angular ranges need to be considered separately to fully exploit the diagnostic potential of two-dimensional light scattering measurements.


PubMed | Imaging Unit, University of British Columbia, British Columbia Cancer Agency and Brookdale University Hospital and Medical Center
Type: | Journal: Biomedical engineering online | Year: 2015

Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions.We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software.The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 m below the epithelial surface were respectively 100, 100, and 92 %.Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical settings.


Lonergan K.M.,Genetics Unit | Chari R.,Genetics Unit | Coe B.P.,Genetics Unit | Wilson I.M.,Genetics Unit | And 6 more authors.
PLoS ONE | Year: 2010

Background: Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease. Methodology/Principal Findings: Through the construction and analysis of SAGE libraries, we have determined transcriptome profiles for preinvasive carcinoma-in-situ (CIS) and invasive squamous cell carcinoma (SCC) of the lung, and compared these with expression profiles generated from both bronchial epithelium, and precancerous metaplastic and dysplastic lesions using Ingenuity Pathway Analysis. Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions. Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer. Genes related to tissue fibrosis and acute phase immune response are characteristic of the invasive SCC phenotype. Moreover, the data presented here suggests that tissue remodeling/fibrosis is initiated at the early stages of CIS. Additionally, this study indicates that alteration in copy-number status represents a plausible mechanism for differential gene expression in CIS and invasive SCC. Conclusions/Significance: This study is the first report of large-scale expression profiling of CIS of the lung. Unbiased expression profiling of these preinvasive and invasive lesions provides a platform for further investigations into the molecular genetic events relevant to early stages of squamous NSCLC development. Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection. © 2010 Lonergan et al.


Arifler D.,Middle East Technical University | Guillaud M.,Imaging Unit
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2015

Optical scattering provides an intrinsic contrast mechanism for the diagnosis of early precancerous changes in tissues. There have been a multitude of numerical studies targeted at delineating the relationship between cancer-related alterations in morphology and internal structure of cells and the resulting changes in their optical scattering properties. Despite these efforts, we still need to further our understanding of inherent scattering signatures that can be linked to precancer progression. As such, computational studies aimed at relating electromagnetic wave interactions to cellular and subcellular structural alterations are likely to provide a quantitative framework for a better assessment of the diagnostic content of optical signals. In this study, we aim to determine the influence of structural length-scale variations on two-dimensional light scattering properties of cells. We numerically construct cell models with different lower bounds on the size of refractive index heterogeneities and we employ the finite-difference time-domain method to compute their azimuth-resolved light scattering patterns. The results indicate that changes in length-scale variations can significantly alter the two-dimensional scattering patterns of cell models. More specifically, the degree of azimuthal asymmetry characterizing these patterns is observed to be highly dependent on the range of length-scale variations. Overall, the study described here is expected to offer useful insights into whether azimuth-resolved measurements can be explored for diagnostic purposes. © 2015 SPIE.


Chari R.,Genetics Unit | Thu K.L.,Genetics Unit | Thu K.L.,University of British Columbia | Wilson I.M.,Genetics Unit | And 12 more authors.
Cancer and Metastasis Reviews | Year: 2010

Advances in high-throughput, genome-wide profiling technologies have allowed for an unprecedented view of the cancer genome landscape. Specifically, high-density microarrays and sequencing-based strategies have been widely utilized to identify genetic (such as gene dosage, allelic status, and mutations in gene sequence) and epigenetic (such as DNA methylation, histone modification, and microRNA) aberrations in cancer. Although the application of these profiling technologies in unidimensional analyses has been instrumental in cancer gene discovery, genes affected by low-frequency events are often overlooked. The integrative approach of analyzing parallel dimensions has enabled the identification of (a) genes that are often disrupted by multiple mechanisms but at low frequencies by any one mechanism and (b) pathways that are often disrupted at multiple components but at low frequencies at individual components. These benefits of using an integrative approach illustrate the concept that the whole is greater than the sum of its parts. As efforts have now turned toward parallel and integrative multidimensional approaches for studying the cancer genome landscape in hopes of obtaining a more insightful understanding of the key genes and pathways driving cancer cells, this review describes key findings disseminating from such high-throughput, integrative analyses, including contributions to our understanding of causative genetic events in cancer cell biology. © 2010 Springer Science+Business Media, LLC.


Zurawska J.H.,University of British Columbia | Jen R.,University of British Columbia | Lam S.,University of British Columbia | Lam S.,Imaging Unit | And 3 more authors.
Chest | Year: 2012

Lung cancer is the leading cause of cancer-related mortality in the United States and around the world. There are >90 million current and ex-smokers in the United States who are at increased risk of lung cancer. The published data from the National Lung Screening Trial (NLST) suggest that yearly screening with low-dose thoracic CT scan in heavy smokers can reduce lung cancer mortality by 20% and all-cause mortality by 7%. However, to implement this program nationwide using the NLST inclusion and exclusion criteria would be extremely expensive, with CT scan costs alone > $2 billion per annum. In this article, we offer a possible low-cost strategy to risk-stratify smokers on the basis of spirometry measurements and emphysema scoring by radiologists on CT scans. © 2012 American College of Chest Physicians.


Pahlevaninezhad H.,Imaging Unit | Lee A.M.D.,Imaging Unit | Shaipanich T.,Imaging Unit | Raizada R.,Imaging Unit | And 6 more authors.
Biomedical Optics Express | Year: 2014

We present a power-efficient fiber-based imaging system capable of co-registered autofluorescence imaging and optical coherence tomography (AF/OCT). The system employs a custom fiber optic rotary joint (FORJ) with an embedded dichroic mirror to efficiently combine the OCT and AF pathways. This three-port wavelength multiplexing FORJ setup has a throughput of more than 83% for collected AF emission, significantly more efficient compared to previously reported fiber-based methods. A custom 900 μm diameter catheter - consisting of a rotating lens assembly, double-clad fiber (DCF), and torque cable in a stationary plastic tube - was fabricated to allow AF/OCT imaging of small airways in vivo. We demonstrate the performance of this system ex vivo in resected porcine airway specimens and in vivo in human on fingers, in the oral cavity, and in peripheral airways. © 2014 Optical Society of America.

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