Relevant Degree Programs
Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - Nov 2019)
Lung cancer has an 18% five year survival rate, which is among the lowest in all cancer types. Typically, this low survival rate is due to the detection of the disease at a late stage not amendable to curative therapy. To combat this poor prognosis, many efforts have been made to detect early lung cancers before they become metastatic. Diagnosis of lung cancer involves localization and biopsy but the diagnostic accuracy of small lung lesions is currently sub-optimal. In the central airways autofluorescent bronchoscopy can localize suspicious areas for biopsy with high sensitivity but the specificity is relatively low. In the peripheral airways abnormal tissue is localized through the radial endobronchial ultrasound procedure. The diagnostic yield is relatively low in the sixty percent range, therefore, there remains a need for real time detailed information about benign versus malignant lung tissue for endoscopic diagnosis. Raman spectroscopy, a technique that utilizes the inelastic scattering of light by a molecule, has the ability to show detailed biochemical information that current procedures do not provide. Here we study the feasibility of incorporating Raman spectroscopy into standard clinical procedures. In the central airways we conduct a large scale single centre trial using Raman Spectroscopy as an adjunct to autofluorescence bronchoscopy procedures. It was found that adjunct RS can greatly improve the classification of malignant from benign/normal lesions with a high diagnostic sensitivity (90%) and good specificity (65%). In the peripheral airways, we present the design and development of a novel miniature Raman probe capable of navigating the bronchial architecture into the small airways. To our knowledge, we show the first in vivo clinical test of a fibre bundle peripheral probe and the first Raman spectra of peripheral lung cancer and normal tissue. With follow up clinical testing and validation we believe the opportunity to use Raman spectroscopy as an adjunct device in the entire lung is feasible.
Accurate and early diagnosis of skin diseases will improve clinical outcomes. Visual inspection alone has limited diagnostic accuracy, while biopsy followed by histopathology examination is invasive and time-consuming. The objective is to design and develop a multimodal optical instrument that provides biochemical and morphological information on human skin in vivo. Raman spectroscopy (RS) is capable of providing biochemical information of tissues. Reflectance confocal microscopy (RCM), which generates micron-level resolution images with capability of optical sectioning, can provide refractive-index-based morphological information of the skin. Multiphoton microscopy (MPM) could simultaneously provide biochemistry-based morphological information from two-photon fluorescence (TPF) and second-harmonic-generation (SHG) images. The thesis hypothesis is that a multimodality instrument combining RS, RCM, and MPM could be developed and provide complementary information in real-time for in vivo skin evaluation and aiding non-invasive diagnosis. A confocal Raman spectroscopy system was initially developed and tested in a study on in vivo mouse skin. Spectral biomarkers (899 and 1325-1330 cm-¹) were found to differentiate tumor-bearing skin from normal skin. A RCM system was then integrated with the spectroscopy system to guide spectral measurements. Noninvasive morphological and biochemical analysis was performed on ex vivo and in vivo human skin. The system was further enhanced by adding an MPM module that can image cellular structures with TPF signals from keratin, NADH, and melanin, as well as image elastic and collaii gen fibers via TPF and SHG signals, respectively. The finalized system was utilized to noninvasively measure a cherry angioma lesion and its surrounding structures on the skin of a volunteer. Confocal Raman spectra from various regions-of-interest acquired under the guidance of MPM and RCM imaging showed different spectral patterns for blood vessels, keratinocytes, and dermal fibers. The system was also successfully used to perform imaging directed two-photon absorption based photothermolysis on ex vivo mouse skin. All the results showed positive evidence, well supporting the overall hypothesis. The developed multimodality system, capable of acquiring co-registered RCM, TPF and SHG images simultaneously at video-rate, and performing image-guided region-of-interest Raman spectral measurements of human skin in vivo, is a powerful tool for non-invasive skin evaluation and diagnosis.
Master's Student Supervision (2010 - 2018)
Viruses are the most abundant biological entity in aquatic ecosystems. In each milliliter of marine or fresh water, there are typically between one to ten million viruses. Aquatic viruses influence microbial diversity, mortality and evolution, which in turn affect biogeochemical cycles and energy fluxes in marine ecosystems. As most aquatic microbes have not been cultured, the viruses which infect them cannot be cultured; hence, non-culture based approaches are needed to ascertain changes in the composition and diversity of virus communities.This research involves using PCR amplicons and high-throughput sequencing to uncover unknown diversity in marine and freshwater viruses and determine its temporal and spatial variation. Differences in the taxonomic profiles of viruses in the families Phycodnaviridae, Myoviridae, and Podoviridae across marine locations were assessed using 454 pyrosequencing. Temporal and spatial changes in the taxonomic profiles of viruses in the family Myoviridae were assessed in a stream using Illumina sequencing.Results show that high-throughput sequencing of marker genes is a robust method to explore viral diversity, and revealed many previously unknown Operational Taxonomic Units (OTUs). Furthermore, distributions of OTUs within virus families differed markedly among samples, indicating that the virus distributions were spatially dynamic. Moreover, the variation of OTUs within the freshwater Myoviridae communities suggested that some OTUs could be used as indicators of agricultural runoff.
Lung cancer is the top cancer killer in Canada and North America. Current lung cancerdetection tools involving X-ray, CT and bronchoscopy are relatively time-consuming andcostly. Breath analyses done by mass spectrometry have shown that certain endogenousvolatile organic compounds (VOCs) are related to lung cancer and revealed the potential ofbreath analysis for lung cancer detection. But mass spectrometry is costly and has slowturnaround times. Raman spectroscopy is a promising candidate for breath analysis because itcan offer unique fingerprint-type signals for molecular identification. Hollow core-photoniccrystal fibre (HC-PCF) is a novel light guide which allows light to be guided in a smallhollow core and it can be filled with a gaseous sample (i.e., human breath) for spectralanalysis. Our objective is to develop a simple, cost-effective and non-invasive tool based onRaman spectroscopy for breath analysis and potentially lung cancer screening.A Raman-gas analyzer was designed, based on photonics technology. A gas supply systemwas built to provide a sealed environment for the loading and unloading of gaseous samples.A laser source at 785 nm was used as the pump for molecular excitation. Stokes Ramansignals generated in the hollow core of the HC-PCF can be guided by collection optics andanalyzed by a Raman spectrometer. Raman spectra have been obtained successfully from air,reference gases (hydrogen gas, oxygen gas, carbon dioxide gas), and human breath. The limitof detection of the system was found to be approximately 15 parts per million by CO²concentration in the ambient air, characterized by the Raman peaks at 1286 cm₋¹ and 1388cm-1. This is more than a 100-fold improvement over the recently reported detection limit with a reflective capillary fibre-based Raman cell. Furthermore the detection limit can be further improved by changes to the optical configurations, optimizing the interaction length of the HC-PCF and possible pre-concentration method to enhance signal-to-noise ratio. This work demonstrated a working prototype of a simple, compact, and cost-effective Raman-gas analyzer based on hollow core photonic crystal fibre, which could potentially be used for lung cancer screening through breath analysis.