Optical molecular imaging for biomedical research

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Optical molecular imaging is a promising emerging technology that offers significant advances in medical physics. The long term objective of my research program is to develop optical molecular imaging tools for biological discovery, that facilitate quantitative and rapid analysis, and have the potential for future clinical translation. Within the scope of this Discovery grant, the initial research uses ovarian cancer as the biological model. The optical molecular imaging tools developed in the course of this research, however will have broad applicability and could be adapted in the future to image other disease models. ***Ovarian cancer is the most lethal of gynecological cancers and is the fifth leading cause of cancer death among women in Canada. It is a prime example of a disease that is very difficult to detect, due to the lack of overt symptoms. Despite the many advances intended to enhance response to treatment, the survival rate in ovarian cancer has only marginally improved in the past few decades. Immense progress could be made if very early neoplastic changes in the Ovarian Surface Epithelium (OSE) cells and tissue could be detected and if factors that cause the disease could be better understood. Moreover, the ability to predict the response to treatment could result in improved patient survival. With this motivation, the short term objectives of my research are:***Objective 1) Determine optical biomarkers to distinguish between normal and variant OSE cells and tissue.***Objective 2) Quantify the efficiency of optical techniques to measure the treatment response of ovarian cancer cells and tissue in vitro.***We will employ Raman Spectroscopy combined with statistical multivariate analysis, to develop high-accuracy models for discriminating between different types of mouse OSE cells in heterogeneous cell populations. The Raman spectrum provides a molecular fingerprint of the chemical composition of a living cell, so subtle biochemical differences between specimens can be extracted out. However this technique is limited for fast chemical imaging. Stimulated Raman Scattering (SRS) is based on nonlinear coherent Raman scattering and is ideally suited for this purpose. We will utilize SRS imaging combined with other nonlinear optical techniques such as two photon excitation fluorescence (TPEF) and second harmonic generation (SHG) imaging to address the short-term objectives set for this research program.***Optical molecular imaging techniques developed in this research will help accelerate the work of ovarian cancer researchers intent on discovering the fundamental mechanisms of the disease and its treatment. This work will provide a more promising route for future clinical translational, which is the eventual long-term objective of this research program. Highly qualified personnel (HQP) at all levels will be trained and actively engaged in this highly interdisciplinary research endeavor.**