Sensitive and Specific Molecular Imaging of Pulmonary Nodules

一个基本的需要是确定在癌症患者的高危人群中检测到的肺部病变 分辨率CT扫描均为转移性病变。虽然CT具有非凡的敏感性，但它缺乏对 做出这一关键的区分。因此，我们研究的长期目标是开发一种新的层析成像技术 分子特异性高的非侵入性标记和检测肺部癌细胞的成像方法 决议。我们的方法使用超极化(HP)气体磁共振成像来可视化癌细胞 以肿瘤特异性功能化氧化铁纳米粒(SPION)为靶点。本应用程序的目标是 目的是在小鼠转移癌模型中优化这一演示方法，建立其理论和实验模型 实际检测限，并直接将该方法与Micro-CT进行比较，同时用组织学方法建立 事实真相。中心假设是，这种新的成像方法将超过CT的灵敏度，而 增加了区分转移性和良性病变所需的分子特异性。该计划的基本原理 拟议的研究是开发一种可以非侵入性地表征肺结节的技术 具有高度的敏感性和特异性，不仅可以改善患者的预后，还可以推动肺部的进步 癌症研究。因此，拟议的研究与国家卫生研究院任务中与以下有关的部分有关 通过发展和加快生物医药技术的应用来改善健康。以Strong为指导 初步数据，将通过追求三个具体目标来检验中心假设：1)建立 理论和实际检测极限，2)优化图像采集、SPION传输和肿瘤 3)直接将该方法的敏感性和特异性与CT进行比较。完成 在这些目标中，将把这项技术定位于临床翻译。第一个目标是建立一个理论模型。 SPION图像对比，并通过成像HP气体流过包含井的体模来验证模型 表征了SPION的分布，并逐渐变得更小。第二个目标是开发和测试一个 图像采集策略可提高灵敏度，优化SPION的静脉给药以实现成像 Spion前后的目标定位，并实施增强的图像分析方法，以进一步提高 该方法的检测灵敏度。最终目标是将完全优化的方法与Micro-CT进行比较 建立转移癌与非癌病变混合的小鼠模型。建议的方法是 创新是因为它结合了两项尖端技术，在分子领域实现了潜在的量子飞跃 对肺中的癌细胞进行成像--这是一个历来对成像构成巨大挑战的器官。这个 提出的研究具有重要意义，因为正在开发的成像方法开辟了一种全新的 对肺转移的敏感检测和分子特征的能力，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.