Tissue Oxygen (pO2) Measurement by Photoacoustic Imaging

描述（由申请人提供）：肿瘤缺氧在许多癌症类型中都存在。它被认为是新生脉管系统无组织生长的结果。靠近血管的癌细胞由于增殖迅速，耗氧量高。距离较远的细胞无法获得氧气供应。这些缺氧癌细胞大多处于细胞周期停滞阶段，因此对主要影响分裂细胞的化疗和放疗具有高度耐药性。针对缺氧肿瘤，研究了不同的治疗技术。为了预测放射治疗对癌症患者的疗效并选择最佳治疗策略，评估组织中的氧分布是必不可少的。然而，现有的评估组织氧合的方法尚未在临床领域建立。在本R21应用中，我们建议开发一种非侵入性、高分辨率的组织氧成像方法。基于近年来光声探测氧敏染料寿命的研究进展，我们提出了一种将时间分辨荧光法的准确性和灵敏度与光声成像的高分辨率和深穿透性相结合的技术。它有可能填补快速、易于使用、实时肿瘤缺氧成像的空白。本研究计划涉及开发这种新成像方法的基本方面。首先，我们将建立一个原型系统，将在幽灵上进行测试。这将是我们优化系统硬件设计和软件算法的主要工具。然后，我们将测试该系统，并在小动物身上比较不同的染料给药方法。这些结果将作为将其转化为临床工具的持续研究的基础。我们对该项目的最终结果的愿景是一种非侵入性临床成像模式，为大多数头颈部癌症（肿瘤可被光线穿透）提供更好的预后和治疗决策。对于较深的肿瘤位置（如乳腺癌肿瘤），将考虑采用侵入性光纤照明。这种成像方式将对肿瘤学尤其是放射肿瘤学的临床实践产生深远的影响。

DESCRIPTION (provided by applicant): Tumor hypoxia is observed in many cancer types. It is believed to be a consequence of unorganized growth of new vasculature. Cancer cells close to the blood vessels have high oxygen consumption due to rapid proliferation. Cells that are farther away are masked from oxygen supply. These hypoxic cancer cells are mostly in a phase of cell cycle arrest and therefore become highly resistant to chemotherapy and radiation therapy which mostly affects dividing cells. Different therapy techniques have been studied to target hypoxic tumors. To predict the efficacy of radiation therapy for a cancer patient and to select optimal therapy strategy it is essential to assess oxygen distribution in the tissue. However, none of the existing methods for assessing tissue oxygenation has yet been established in the clinical arena. In this R21 application we propose to develop a non-invasive, high resolution imaging method for tissue oxygen. Based on our recent development of photoacoustic probing of oxygen sensitive dye's lifetime, we propose a technique that combines the accuracy and sensitivity of time-resolved fluorescence methods with the high resolution and deep penetration of photoacoustic imaging. It has the potential to fill the gap for a fast, easy to use, real-time imaging of tumor hypoxia. This research proposal addresses the basic aspects of developing this new imaging method. First, we will build a prototype system that will be tested on phantoms. This would be our prime vehicle for optimizing the system hardware design and software algorithms. Then we will test the system and compare different dye administration methods on small animals. These results will serve as a basis for a continuing research to translate it into a clinical tool. Our vision for the ultimate outcome of this project is a non-invasive clinical imaging modality for better prognosis and treatment decision making in most cases of head and neck cancers (where tumor is accessible to light penetration). For deeper tumor locations (e.g. breast cancer tumors) invasive optical fiber illumination will be considered. Such imaging modality could have a profound impact on clinical practice in oncology and particularly in radiation oncology.