In Vivo Cancer Therapy Monitoring with Diffuse Optical Methods

描述（由申请人提供）：我的长期目标是评估和提高漫射光学方法在乳腺癌检测、诊断和治疗监测中的能力。使用近红外光的漫射光学方法提供了几个独特的功能参数（如总血红蛋白浓度、血氧饱和度、血流量、水和脂质浓度），以增强肿瘤的敏感性和特异性。此外，深层组织微环境（如血管渗漏、酸性）可以通过漫射荧光成像/光谱进行探测。漫射光学方法可以在早期阶段影响癌症治疗的监测和计划，因为治疗引起的代谢变化可能先于临床触诊或传统成像方式测量的解剖大小变化。我在宾夕法尼亚大学从事漫射光学断层扫描以检测和表征乳腺癌已有10年了。我在仪器仪表和数值分析方面获得了良好的教育和经验，也获得了宝贵的临床经验。然而，随着研究的迅速发展和向临床领域的扩展，需要更深入的生物医学培训来将漫射光学技术转化为临床。因此，我建议在我的导师，物理系的Arjun Yodh博士和共同导师Mitchell Schnall博士，放射科的Jerry Glickson博士和血液科肿瘤科的Angela DeMichele博士的指导下拓展我的视野。在这个指导阶段（K99），我将接受肿瘤生物学和生理学以及生物统计学的基础训练。对于K99的研究，我将探索便携式漫射光学装置在评估乳腺癌患者新辅助化疗反应中的应用。在随后的独立研究者阶段（ROO）中，我将比较使用一种浓度对应葡萄糖水平的新型光学染料的荧光漫射光学方法与放射自显影/PET对人乳腺癌小鼠异种移植模型的影响。一旦我确定了这种染料的性能，我将把它作为葡萄糖代谢的替代标记物。我将研究所有光学方法同时监测葡萄糖和氧代谢是否可以增强对治疗效果的评估。这项独立的研究将为分子成像在体内用于治疗监测和诊断铺平道路，当它可用于人类时。

DESCRIPTION (provided by applicant): My long-range goal is to assess and improve the capability of diffuse optical methods in detection, diagnosis and therapeutic monitoring of breast cancer. Diffuse optical methods using near-infrared light provide several unique functional parameters (such as total hemoglobin concentration, blood oxygen saturation, blood flow, water and lipid concentration) to enhance tumor sensitivity and specificity. Moreover, deep tissue micro-environment (e.g. vascular leakiness, acidity) can be probed with diffuse fluorescence imaging/spectroscopy. Diffuse optical methods can impact on cancer therapy monitoring and planning at early stages since the metabolic changes due to therapy may precede the anatomical size changes measured by clinical palpation or conventional imaging modalities. I have worked on diffuse optical tomography to detect and characterize breast cancer for -10 years at the University of Pennsylvania. I have acquired excellent education and experience in instrumentation and numerical analysis and also got valuable clinical experience. However, as the research is growing rapidly and expanding more into the clinical regime, more in-depth biomedical training is becoming necessary to translate the diffuse optical technology into the clinic. Therefore, I am proposing to expand my horizons under my mentor, Dr. Arjun Yodh from Physics department and co-mentors, Dr. Mitchell Schnall, Dr. Jerry Glickson from Radiology and Dr. Angela DeMichele from Hematology-Oncology. During this mentored phase (K99), I will take courses to get fundamental training on tumor biology and physiology as well as biostatistics. For K99 research, I will explore the utility of portable diffuse optical device to assess neoadjuvant chemotherapy response of subjects with breast cancer. In the subsequent independent investigator phase (ROO), I will compare fluorescence diffuse optical method using a new optical dye whose concentration corresponds to glucose level with autoradiography/PET on mouse xenograft model of human breast cancer. Once I establish the performance of this dye, I will use it as a surrogate marker for glucose metabolism. I will investigate whether simultaneous monitoring of glucose and oxygen metabolism accessible by all optical methods can enhance the assessment of treatment efficacy. This independent research will pave the ways for molecular imaging in vivo for therapy monitoring and diagnosis when it becomes available for human use.