Molecular Photoacoustic Imaging for the Detection of Sentinel Lymph Node Metastas

描述（由申请人提供）：在癌症患者中，确定恶性肿瘤是否已扩散是用于制定治疗计划和预测预后的最重要因素。在大多数情况下，癌细胞最初通过区域淋巴结扩散。因此，临床评估区域淋巴结转移的存在是至关重要的。不幸的是，没有实时的，非侵入性的临床方法，可以可靠地检测和诊断淋巴结中的微转移。因此，临床上迫切需要一种成像技术，其广泛可用、非侵入性且操作简单、安全，并且可以可靠地检测和真实的充分诊断淋巴结微转移。我们研究计划的总体目标是开发一种先进的、体内的、非侵入性的、分子特异性成像技术，即，集成的超声和光声成像结合靶向等离子体纳米传感器，能够真实的实时立即准确评估前哨淋巴结微转移。该项目的第一个目标是开发一个组合的光声和超声成像系统和协议。该系统将包括一个高频超声机与脉冲纳秒可调谐激光器耦合。第二个目标是开发光谱图像处理算法，以检测注射等离子体纳米传感器后的前哨淋巴结转移。成像系统和算法将在与正常细胞和癌细胞孵育的纳米传感器的体外细胞样本上进行测试。最终目的是使用成像系统和光谱算法来检测体内小鼠癌症模型中的淋巴结微转移。影像学结果将与切除淋巴结的组织学相关联。为实现这些目标而提出的培训计划旨在培养具有具体技术专长的实习指导员。选定的导师是超声和光声成像和图像处理方面的专家。PI将参加研究伦理行为的正式培训以及针对其研究领域的培训，为独立研究做好准备。 公共卫生相关性：在癌症患者中，确定恶性肿瘤的扩散是制定治疗计划和预测预后的最重要因素。在大多数情况下，癌细胞最初通过区域淋巴结扩散。因此，诸如分子特异性超声和光声淋巴成像的技术能够在体内、非侵入性和准确地真实的评估区域转移，可以简化和改善对上皮恶性肿瘤患者的管理，显著改善公共健康，并降低医疗成本。

DESCRIPTION (provided by applicant): In cancer patients, determination of whether a malignancy has spread is the single most important factor used to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is of paramount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliably detect and diagnose micrometastases in lymph nodes. Thus, there is an urgent clinical need for an imaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliably detect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in vivo, noninvasive, molecular specific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targeted plasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph node micrometastases in real time. The first aim of the project is to develop a combined photoacoustic and ultrasound imaging system and protocol. The system will consist of a high frequency ultrasound machine coupled with a pulsed nanosecond tunable laser. The second aim is to develop spectroscopic image processing algorithms to detect sentinel lymph node metastasis after the injection of plasmonic nanosensors. The imaging system and algorithms will be tested on in vitro cell samples of nanosensors incubated with normal and cancerous cells. The final aim is to use the imaging system and spectroscopic algorithms to detect lymph node micrometastases in a murine cancer model in vivo. The imaging results will be correlated with histology of the resected lymph nodes. The training plan proposed to accomplish these goals has been designed to establish trainee mentors with specific technical expertise. The selected mentors are experts in ultrasound and photoacoustic imaging and image processing. The PI will enroll in formal training in the ethical conduct of research and in training specific to his research field, to prepare him for independent research. PUBLIC HEALTH RELEVANCE: In cancer patients, the determination of the spread of malignancy is the single most important factor to develop a therapeutic plan and predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Thus, a technology such as molecular specific ultrasound and photoacoustic lymphatic imaging, capable of in-vivo, noninvasive and accurate assessment of regional metastases in real time, can simplify and improve management of patients with epithelial malignancies, significantly improve public health, and reduce medical costs.