Tissue Oxygen (pO2) Measurement by Photoacoustic Imaging

描述（由申请人提供）：在许多癌症类型中观察到肿瘤缺氧。据信这是新脉管系统无组织生长的结果。靠近血管的癌细胞由于快速增殖而具有高耗氧量。较远的细胞被氧气供应所掩盖。这些低氧癌细胞大多处于细胞周期停滞阶段，因此对化疗和放疗具有高度抗性，而化疗和放疗主要影响分裂细胞。已经研究了不同的治疗技术以靶向低氧肿瘤。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，必须评估组织中的氧分布。然而，在临床竞技场中还没有建立用于评估组织氧合的现有方法。 在R21应用中，我们提出开发一种用于组织氧的非侵入性高分辨率成像方法。基于我们最近的发展，光声探测氧敏染料的寿命，我们提出了一种技术，结合时间分辨荧光方法的准确性和灵敏度与光声成像的高分辨率和深穿透。它有潜力填补差距，快速，易于使用，实时成像的肿瘤缺氧。 这项研究计划涉及开发这种新成像方法的基本方面。首先，我们将构建一个原型系统，并在Phanomenon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，并比较不同的染料管理方法的小动物。这些结果将作为继续研究的基础，将其转化为临床工具。 我们对该项目最终成果的愿景是一种非侵入性临床成像模式，用于在大多数头颈部癌症（肿瘤可被光穿透）病例中进行更好的预后和治疗决策。对于较深的肿瘤位置（例如乳腺癌肿瘤），将考虑侵入性光纤照明。这种成像模式可能对肿瘤学，特别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.