Sensitive and Specific Molecular Imaging of Pulmonary Nodules

基本上需要确定在癌症患者的高血压上检测到的肺部病变是否是一种恶性肿瘤。 分辨率CT扫描是转移性疾病。虽然CT具有非凡的灵敏度，但它缺乏特异性， 做出这个重要的区分。因此，我们研究的长期目标是开发一种新的层析成像技术， 成像方法，以非侵入性标记和检测肺中的癌细胞，具有分子特异性和高 分辨率我们的方法使用超极化（HP）气体MR成像来可视化已经被破坏的癌细胞。 通过肿瘤特异性功能化氧化铁纳米颗粒（SPION）靶向。本申请的目的 在小鼠转移癌模型中优化该方法，建立其理论和 实际的检测限，并直接比较这种方法的显微CT，同时使用组织学建立 地面实况核心假设是这种新的成像方法将超过CT的灵敏度， 增加了区分转移性和良性病变所需的分子特异性。的理由 建议的研究是开发一种可以非侵入性地表征肺结节的技术 具有高灵敏度和特异性，不仅可以改善患者的预后， 癌症研究。因此，拟议的研究与NIH使命的一部分有关， 通过发展和加速应用生物医学技术来改善健康状况。以强为导 初步数据，中心假设将通过追求三个具体目标进行测试：1）建立 理论和实际检测限，2）优化图像采集、SPION输送和肿瘤 3）直接与CT比较方法的敏感性和特异性。完成 这些目标将使这项技术用于临床转化。第一个目标是建立一个理论模型， SPION图像对比度，并通过对流过包含井的体模的HP气体进行成像来验证模型。 特征性的，并且SPION的分布逐渐变小。第二个目标是开发和测试一种 提高灵敏度的图像采集策略，优化SPION的静脉输送，以实现成像 前和后SPION目标，并实施增强的图像分析方法，以进一步提高 方法的检测灵敏度。最终目的是将完全优化的方法与微型CT进行比较， 对转移性癌症与非癌性病变混合小鼠模型进行成像。所提出的方法是 创新，因为它结合了两种尖端技术，在分子水平上实现了潜在的量子飞跃。 肺中癌细胞的成像--肺是一个在历史上提出了巨大成像挑战的器官。的 拟议的研究是重要的，因为正在开发的成像方法开辟了一个全新的 灵敏检测和分子表征肺转移的能力，以及更广泛的 使肺部的高分辨率分子成像成为可能。

A fundamental need exists to determine whether pulmonary lesions detected on a cancer patient's high- resolution CT scan are metastatic disease. While CT has extraordinary sensitivity, it lacks the specificity to make this critical distinction. The long-term goal of our research, therefore, is to develop a new tomographic imaging method to non-invasively tag and detect cancer cells in the lungs with molecular specificity and high resolution. Our approach uses hyperpolarized (HP) gas MR imaging to visualize cancer cells that have been targeted by tumor-specific functionalized Iron Oxide Nanoparticles (SPIONs). The objective of this application is to optimize this demonstrated method in mouse models of metastatic cancer, establish its theoretical and practical detection limits, and directly compare this method to micro-CT, while using histology to establish ground truth. The central hypothesis is that this new imaging method will surpass the sensitivity of CT, while adding the molecular specificity needed to distinguish metastatic from benign lesion. The rationale for the proposed research is that development of a technique that can non-invasively characterize pulmonary nodules with high sensitivity and specificity will not only improve patient outcomes, but also drive progress in lung cancer research. Thus, the proposed research is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating the application of biomedical technologies. Guided by strong preliminary data, the central hypothesis will be tested by pursuing three Specific Aims: 1) Establish the theoretical and practical detection limits, 2) Optimize the image acquisition, SPION delivery, and tumor visualization methods, and 3) Directly compare the method's sensitivity and specificity against CT. Completion of these aims will position this technology for clinical translation. The first aim establishes a theoretical model of SPION image contrast and validates the model by imaging HP gas flowing through a phantom containing well- characterized, and progressively smaller distributions of SPIONs. The second aim will develop and test an image acquisition strategy to increase sensitivity, optimize intravenous delivery of SPIONs to enable imaging pre- and post-SPION targeting, and implement an enhanced image analysis approach to further increase the detection sensitivity of the method. The final aim compares the fully optimized method against micro-CT to image mouse models of metastatic cancer mixed with non-cancerous lesions. The proposed approach is innovative because it combines two cutting-edge technologies to take a potential quantum leap in molecular imaging of cancer cells in the lung-an organ that has historically posed enormous imaging challenges. The proposed research is significant because the imaging method being developed opens up an entirely new capacity for sensitive detection and molecular characterization of pulmonary metastases, and more broadly enables high-resolution molecular imaging in the lung to become feasible.