Diffuse Optical Monitoring of Head and Neck Tumor Therapy

项目摘要： 放射治疗或化学放射治疗是头颈部癌症的标准疗法，但这 众所周知，治疗在患有缺氧肿瘤的患者中不太有效。此外，癌症治疗 可能改变肿瘤的生理状态，从而影响治疗效果。调节肿瘤的因素 氧合包括血流、血液氧合、氧代谢和尼古丁水平（即，烟草使用）。 然而，肿瘤血流动力学和代谢在癌症治疗期间不是常规测量的，这是由于肿瘤的血流动力学和代谢在癌症治疗期间是常规测量的。 缺乏适当的技术。计算机断层扫描（CT）和磁共振成像（MRI）是 目前可用的最佳可重复方法，用于测量选择用于客观缓解的靶病灶 评估，但这些方式需要大型和昂贵的仪器，严重限制了其日常使用 在诊所里。漫射光学系统连续监测肿瘤血流动力学和代谢的能力 最近在我们的初步研究中已经证明了在临床床边治疗期间。的 本项目的目的是开发和优化一种无创的多功能多模态临床光学 这是一种有助于在尽可能早的阶段评估和预测肿瘤反应的工具。更 具体地，该光学仪器将监测和预测对化疗的血液动力学和代谢反应， 头颈部肿瘤的放射治疗我们假设，肿瘤生理功能评估 治疗期间的状态和动态变化将为长期治疗的早期预测提供信息 结果，从而使临床医生能够以时间敏感的方式优化每个患者的治疗。实现 这一目标，我们将组装一个混合流和氧气系统，结合新开发的扩散 相关光谱（DCS）流量计与商业组织血氧计，用于同时测量 肿瘤血流量、氧合和氧代谢（从流量和氧合数据导出）。的 将对包括光学探头和软件平台在内的仪器进行测试和优化， 纵向监测肿瘤生理状态和血流动力学/代谢变化之前，期间和 吸烟者和非吸烟者（n=125）治疗后。预计， 将观察到治疗结果之间的相关性（例如，肿瘤体积变化、肿瘤毒性、至 疾病复发、存活）和肿瘤生理状态和变化以及尼古丁水平。不同 不同类型的生理参数可能显示出每个患者对癌症治疗的不同敏感性， 可以揭示影响个体治疗结果的主要因素。我们的新型混合光学系统将 提供血流动力学和代谢成像对比，作为CT和MRI的补充， 在早期评估和预测癌症治疗反应方面具有独特的潜力。我们的长期目标是发展 强大的科学合作，在早期阶段优化和个性化癌症治疗， 光学技术。

Project Summary: Treatment with radiation or chemo-radiotherapy is the standard therapy for head and neck cancers but this treatment is well known to be less efficacious in patients with hypoxic tumors. Furthermore, cancer therapy may alter tumor physiological status, thus impacting treatment efficacy. Factors that modulate tumor oxygenation include blood flow, blood oxygenation, oxygen metabolism, and nicotine levels (i.e., tobacco use). Tumor hemodynamics and metabolism, however, are not routinely measured during cancer therapy due to the lack of appropriate technologies. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the best currently available and reproducible methods to measure target lesions selected for objective response assessment, but these modalities require large and costly instrumentation that severely limits their routine use in clinics. The capabilities of diffuse optics for continuously monitoring tumor hemodynamics and metabolism during therapy at the clinical bedside have recently been demonstrated in our preliminary studies. The objective of this project is to develop and optimize a noninvasive versatile multi-modality clinical optical instrument to aid in evaluating and predicting tumor responses at the most early stage possible. More specifically, this optical instrument will monitor and predict hemodynamic and metabolic responses to chemo- radiotherapy in head and neck tumors. We hypothesize that functional assessment of tumor physiological status and dynamic changes during therapy will provide information for early prediction of long-term treatment outcomes, thus enabling clinicians to optimize therapy for each patient in a time sensitive fashion. To achieve this goal, we will assemble a hybrid flow and oxygen system that combines a newly developed diffuse correlation spectroscopy (DCS) flowmeter with a commercial tissue-oximeter for simultaneous measurement of tumor blood flow, oxygenation, and oxygen metabolism (derived from the flow and oxygenation data). The instrument including optical probes and a software platform will be tested and optimized for continuous and longitudinal monitoring of tumor physiological status and hemodynamic/metabolic changes before, during and after therapy in patients including smokers and nonsmokers (n=125). It is anticipated that significant correlations will be observed between therapy outcomes (e.g., tumor volume change, tumor toxicity, time to disease recurrence, survival) and tumor physiological status and changes as well as nicotine levels. Different types of physiological parameters may show different sensitivities to cancer therapy in each patient, which could reveal the primary factor(s) affecting individual therapy outcomes. Our novel hybrid optical system will provide hemodynamic and metabolic imaging contrasts complementary to those of CT and MRI, and holds unique potential for early evaluating and predicting cancer therapy responses. Our long-term goal is to develop robust scientific collaborations to optimize and individualize cancer therapy at early stages with noninvasive optical technologies.