Optical molecular imaging for biomedical research

光学分子成像是一项很有前途的新兴技术，它在医学物理学方面取得了重大进展。我的研究计划的长期目标是开发用于生物学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。在这笔探索基金的范围内，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，并可能在未来适用于对其他疾病模型进行成像。 卵巢癌是最致命的妇科癌症，是加拿大女性癌症死亡的第五大原因。这是一种由于缺乏明显症状而很难被发现的疾病的典型例子。尽管有许多旨在提高治疗反应的进展，但在过去的几十年里，卵巢癌的存活率只有轻微的提高。如果能够检测到卵巢表面上皮(OSE)细胞和组织的早期肿瘤性变化，如果能够更好地了解导致疾病的因素，就可能取得巨大的进展。此外，预测治疗反应的能力可能会提高患者的存活率。在这种动机下，我的研究的短期目标是： 目的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)量化光学技术在卵巢癌细胞和组织体外治疗反应中的作用。 我们将使用拉曼光谱和统计多变量分析相结合的方法，开发高精度的模型来区分不同细胞群中不同类型的小鼠OSE细胞。拉曼光谱提供了活细胞化学成分的分子指纹，因此可以提取样本之间的细微生化差异。然而，这项技术在快速化学成像方面受到限制。受激拉曼散射(SRS)是基于非线性相干拉曼散射的，非常适合于这一目的。我们将利用SRS成像与其他非线性光学技术相结合，如双光子激发荧光(TPEF)和二次谐波(SHG)成像，以解决为这一研究计划设定的短期目标。 这项研究开发的光学分子成像技术将有助于加快卵巢癌研究人员的工作，目的是发现这种疾病的基本机制及其治疗。这项工作将为未来的临床翻译提供一条更有前途的路线，这也是本研究计划的最终长期目标。所有级别的高素质人员(HQP)将接受培训，并积极参与这一高度跨学科的研究工作。

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.