In Vivo Cancer Therapy Monitoring with Diffuse Optical Methods

我的长期目标是评估和提高漫反射光学方法在检测、诊断 和乳腺癌的治疗监测。使用近红外光的漫射光学方法提供 几个独特的功能参数(如总血红蛋白浓度，血氧饱和度， 血流、水和脂肪浓度)，以提高肿瘤的敏感性和特异性。此外，深 组织微环境(如血管渗漏、葡萄糖代谢)可以用弥散效应来探测 荧光成像/光谱学。漫反射光学方法可以影响癌症治疗监测和 在早期阶段进行计划，因为治疗引起的代谢变化可能先于解剖大小 改变。在指导的K99阶段，我探索了便携式漫反射光学设备的用途，以评估 接受肿瘤培训的乳腺癌患者的新辅助化疗反应 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 旨在通过引入荧光检测来扩展扩散光学器件的监测能力。 使用新的靶向光学荧光染料，人们可以探测肿瘤的特异性代谢和生理变化 仅靠内源性对比就能达到。特别是，我将探索脱氧葡萄糖类似物荧光 染料用于测试其探测葡萄糖代谢的能力，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基础研究平台 用于量化内源和外源的模型和漫反射光学成像/光谱系统 肿瘤对比度准确。荧光染料的生物分布、药代动力学、 用显微和宏观荧光检测小鼠移植瘤模型的肿瘤与正常对照 成像技术，并将与放射自显影和正电子发射计算机断层扫描进行比较。然后，我会调查是否 通过所有光学方法可以同时监测葡萄糖和氧代谢，可以增强 治疗效果的评估。本研究将为体内分子成像研究奠定基础。 当它可供人类使用时，监测治疗。

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.