Optical molecular imaging for biomedical research

光学分子成像是一种有前途的新兴技术，为医学物理学提供了重大进展。我的研究计划的长期目标是开发用于生物发现的光学分子成像工具，促进定量和快速分析，并具有未来临床翻译的潜力。在这项发现资助的范围内，最初的研究使用卵巢癌作为生物模型。然而，在本研究过程中开发的光学分子成像工具将具有广泛的适用性，并可在未来适用于其他疾病模型的成像。* 卵巢癌是最致命的妇科癌症，是加拿大妇女癌症死亡的第五大原因。这是一种很难发现的疾病的一个典型例子，因为缺乏明显的症状。尽管有许多进步旨在提高对治疗的反应，但在过去几十年中，卵巢癌的生存率仅略有提高。如果能够检测到卵巢表面上皮细胞和组织中的非常早期的肿瘤变化，并且如果能够更好地了解导致疾病的因素，则可以取得巨大的进展。此外，预测对治疗的反应的能力可以提高患者的生存率。有了这个动机，我的研究的短期目标是：* 目标1）确定光学生物标志物，以区分正常和变异的OSE细胞和组织。目的2）量化光学技术在体外测量卵巢癌细胞和组织的治疗反应的效率。我们将采用拉曼光谱结合统计多变量分析，开发高精度的模型，用于区分不同类型的小鼠OSE细胞在异质细胞群。拉曼光谱提供了活细胞化学成分的分子指纹，因此可以提取出标本之间细微的生化差异。然而，这种技术对于快速化学成像是有限的。受激拉曼散射（SRS）基于非线性相干拉曼散射，并且非常适合于此目的。我们将利用SRS成像结合其他非线性光学技术，如双光子激发荧光（TPEF）和二次谐波产生（SHG）成像，以解决本研究计划的短期目标。在这项研究中开发的光学分子成像技术将有助于加速卵巢癌研究人员的工作，他们的目的是发现疾病及其治疗的基本机制。这项工作将为未来的临床转化提供更有前途的途径，这是本研究计划的最终长期目标。各级高素质人员（HQP）将接受培训，并积极参与这一高度跨学科的研究奋进。

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.**