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: 8433246
• 负责人: Rosa Tamara Branca
• 金额: $ 28.88万
• 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 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433246
• 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.

一个基本的需要存在于确定是否肺部病变检测到癌症患者的高