Optical molecular imaging for biomedical research

用于生物医学研究的光学分子成像

• 批准号: RGPIN-2015-06154
• 负责人: Murugkar, Sangeeta
• 金额: $ 1.6万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=660501
• 关键词: Optical; molecular; imaging; biomedical; research

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.**

光学分子成像是一项有前途的新兴技术，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。在这项发现基金的范围内，最初的研究使用卵巢癌作为生物学模型。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，并且可以在未来适应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。由于缺乏明显的症状，这是一种非常难以发现的疾病的主要例子。尽管有许多进步旨在提高对治疗的反应，但在过去的几十年里，卵巢癌的存活率只有轻微的提高。如果卵巢表面上皮（OSE）细胞和组织的早期肿瘤改变能够被检测到，如果导致疾病的因素能够得到更好的理解，那么将会取得巨大的进展。此外，预测治疗反应的能力可以提高患者的生存率。基于此动机，我的短期研究目标是：***目的1)确定光学生物标志物来区分正常和变异的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治疗反应的效率。***我们将利用拉曼光谱结合统计多元分析，建立在异质细胞群中区分不同类型小鼠OSE细胞的高精度模型。拉曼光谱提供了活细胞化学成分的分子指纹，因此可以提取出样本之间细微的生化差异。然而，这种技术在快速化学成像方面受到限制。受激拉曼散射（SRS）基于非线性相干拉曼散射，非常适合于这一目的。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）成像来解决为本研究计划设定的短期目标。***本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发现该疾病的基本机制及其治疗方法的工作。这项工作将为未来的临床转化提供更有希望的途径，这是本研究项目最终的长期目标。各级高素质人才（HQP）将得到培训，并积极参与这一高度跨学科的研究工作