Sensitive and Specific Molecular Imaging of Pulmonary Nodules

肺结节的灵敏和特异性分子成像

• 批准号: 8611716
• 负责人: Rosa Tamara Branca
• 金额: $ 29.78万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8611716
• 关键词: Architecture; Benign; Biomedical Technology; Bleomycin; Blinded; Camping; Cancer Patient; Cessation of life; Clinical; Clinical Management; Collaborations; Custom; Data; Detection; Development; Diagnostic; Disease; Disseminated Malignant Neoplasm; Environment; Gases; Goals; Head; Health; Healthcare Systems; Histology; Histopathology; Housing; Image; Image Analysis; Imagery; Imaging Techniques; Imaging technology; Injection of therapeutic agent; Intravenous; Lesion; Lung; Lung nodule; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Metastatic Lesion; Metastatic Neoplasm to the Lung; Methods; Microscopy; Mission; Modality; Modeling; Molecular; Mus; Neoplasm Metastasis; Noble Gases; Organ; Outcome; Patients; Physicians; Positioning Attribute; Positron-Emission Tomography; Predisposition; Primary Neoplasm; Public Health; Pulmonary Pathology; Reader; Relative (related person); Relaxation; Research; Resolution; Sensitivity and Specificity; Specificity; Staging; Techniques; Technology; Testing; Theoretical model; Therapeutic; Time; Translations; United States National Institutes of Health; Visual; Work; X-Ray Computed Tomography; anticancer research; base; cancer cell; cancer imaging; cost; foot; imaging modality; improved; in vivo; innovation; iron oxide; lung imaging; malignant breast neoplasm; minimally invasive; molecular imaging; mouse model; nanoparticle; quantum; success; theories; tool; tumor

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.

存在基本需求，以确定是否在癌症患者的高位上检测到肺部病变 分辨率CT扫描是转移性疾病。尽管CT具有非凡的敏感性，但它缺乏特异性 做出这种临界区别。因此，我们研究的长期目标是开发新的层析成像 非侵入性标记和检测具有分子特异性和高肺中癌细胞的成像方法 解决。我们的方法使用超极化（HP）气体MR成像来可视化已经 由肿瘤特异性功能化氧化铁纳米颗粒（SPIONS）靶向。此应用的目的 是在转移性癌症的小鼠模型中优化这种证明的方法，建立其理论和 实际检测极限，并直接将此方法与Micro-CT进行比较，同时使用组织学建立 地面真相。中心假设是这种新成像方法将超过CT的灵敏度，而 添加区分转移性和良性病变所需的分子特异性。理由 拟议的研究是一种可以非侵入性肺结节的技术的开发 具有高灵敏度和特异性，不仅会改善患者的预后，而且可以推动肺部的进展 癌症研究。因此，拟议的研究与NIH任务的那部分有关 通过开发和加速生物医学技术来改善健康。在强者的指导下 初步数据，中心假设将通过追求三个特定目的来检验：1）确定 理论和实际检测极限，2）优化图像采集，SPION递送和肿瘤 可视化方法和3）直接比较该方法对CT的敏感性和特异性。完成 这些目的将使这项技术定位为临床翻译。第一个目的建立了一个理论模型 SPION图像对比，并通过成像流经包含良好的幻影的HP气体来验证模型 表征，逐渐较小的SPION分布。第二个目标将发展和测试 图像采集策略以提高灵敏度，优化SPION的静脉输送以启用成像 固定前后的定位，并实施增强的图像分析方法，以进一步增加 该方法的检测灵敏度。最终目标将针对Micro-CT的完全优化方法与 转移性癌症的图像小鼠模型与非癌性病变混合。建议的方法是 创新性，因为它结合了两种尖端技术，以在分子中进行潜在的量子飞跃 历史上构成巨大成像挑战的肺部器官中癌细胞的成像。这 拟议的研究很重要，因为开发的成像方法可以打开一个全新的 肺转移敏感检测和分子表征的能力，更广泛地 使肺中的高分辨率分子成像变得可行。

项目成果

Influence of Gold Nanoshell on Hyperthermia of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs).

• DOI: 10.1021/jp105807r
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY C
• 影响因子: 3.7
• 作者: Mohammad, Faruq;Balaji, Gopalan;Weber, Andrew;Uppu, Rao M.;Kumar, Challa S. S. R.
• 通讯作者: Kumar, Challa S. S. R.

Effects of superparamagnetic iron oxide nanoparticles on the longitudinal and transverse relaxation of hyperpolarized xenon gas.

超顺磁性氧化铁纳米颗粒对超极化氙气纵向和横向弛豫的影响。

• DOI: 10.1016/j.jmr.2018.04.001
• 发表时间: 2018
• 期刊: Journal of magnetic resonance (San Diego, Calif. : 1997)
• 作者: Burant,Alex;Antonacci,Michael;McCallister,Drew;Zhang,Le;Branca,RosaTamara
• 通讯作者: Branca,RosaTamara