In Vivo Cancer Therapy Monitoring with Diffuse Optical Methods

我的长期目标是评估和提高漫射光学方法在检测、诊断和治疗中的能力。 和乳腺癌的治疗监测。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（例如总血红蛋白浓度，血氧饱和度， 血流、水和脂质浓度）以增强肿瘤敏感性和特异性。此外，深 组织微环境（例如血管渗漏、葡萄糖代谢）可以用弥散的 荧光成像/光谱学。漫射光学方法可以影响癌症治疗监测， 由于治疗引起的代谢变化可能先于解剖尺寸， 变化在指导K99阶段，我探索了便携式漫射光学设备的实用性，以评估 新辅助化疗反应的人受试者的乳腺癌，并接受培训，在肿瘤 生物学、生物统计学和生物医学成像。拟议的研究建立在K99的初步成功基础上 阶段，旨在通过结合荧光检测来扩展漫射光学的监测能力。 使用新的靶向光学荧光染料，可以探测肿瘤特异性代谢和生理学， 仅通过内源性造影剂即可获得。特别是，我将探讨脱氧葡萄糖类似物荧光 染料，以测试其探测葡萄糖代谢的能力，这已成功地用于PET成像， 治疗监测和诊断。首先，我将建立由动物肿瘤组成的临床前研究平台， 模型和漫射光学成像/光谱系统来量化内源性和外源性 肿瘤对比准确。荧光染料将表征其生物分布，药代动力学， 以及通过显微镜和宏观荧光在小鼠异种移植模型中的肿瘤与正常对照 成像技术，并将比较放射自显影和PET。然后，我将调查是否 通过所有光学方法可同时监测葡萄糖和氧代谢， 治疗效果的评估。这项研究将为活体分子成像铺平道路， 当它可供人类使用时进行治疗监测。

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 concentrations) to enhance tumor sensitivity and specificity. Moreover, deep tissue micro-environment (e.g. vascular leakiness, glucose metabolism) can be probed with diffuse fluorescence imaging/spectroscopy. Diffuse optical methods can impact cancer therapy monitoring and planning at early stages since the metabolic changes due to therapy may precede the anatomical size changes. During the mentored K99 phase, I explored the utility of portable diffuse optical device to assess neoadjuvant chemotherapy response of human subjects with breast cancer, and received trainings in tumor biology, biostatistics and biomedical imaging. The proposed research builds on initial success from K99 phase and aims to expand the monitoring capability of dffuse optics by incorporating fluorescence detection. Using new targeted optical fluorescent dyes, one can probe tumor specific metabolism and physiology not accessible by endogenous contrast alone. In particular, I will explore deoxyglucose analogue fluorescent dye to test its ability to probe glucose metabolism, which has been successfully utilized in PET imaging for therapy monitoring and diagnosis. First, I will build preclinical study platform consisting of animal tumor models and diffuse optical imaging/spectroscopy systems to quantify both endogenous and exogenous tumor contrast accurately. The fluorescent dye will be characterized for its biodistribution, pharmacokinetics, and tumor-to-normal contrast in mouse xenograft model by microscopic and macroscopic fluorescence imaging techniques, and will be compared to autoradiography and PET. Then, I will investigate whether simultaneous monitoring of glucose and oxygen metabolism accessible by all optical methods can enhance the assessment of treatment efficacy. This research will pave the ways for molecular imaging in vivo for therapy monitoring when it becomes available for human use.