MR predictors of infection, inflammation, and structural lung damage in CF

描述(申请人提供)：囊性纤维化(CF)婴儿和幼儿肺部疾病的检测和监测目前是有限的，这是对这一人群的护理和研究取得进展的障碍。在这项建议中，我们假设肺和肺循环的磁共振成像(MRI)有可能成为监测早期CF肺部疾病的灵敏和便携的工具，肺血流灌注和/或结构的变化可以与代谢组学和蛋白质组学方法确定的外周生物标志物相关。该提案将核磁共振技术的进步与新陈代谢组学和蛋白质组学的新兴技术结合起来，将新的磁共振成像与候选和新的途径分析联系起来。我们将通过MRI和CT检查肺血流的三个方面(全肺和局部肺血流、血管阻力和体肺侧支循环血流量)，并与肺的结构评估进行比较。这些研究将在6个月至3岁的CF和非CF对照组中进行，在CF患者中重复测量。将CF与非CF条件(包括氧化状态、嘌呤能信号和葡萄糖代谢)分开的候选代谢组途径将是初始生物标记物分析的重点，先进的生物信息学技术将应用于定义代谢组和成像之间的新关系。(摘要结束)

DESCRIPTION (provided by applicant): Detection and monitoring of lung disease in infants and toddlers with cystic fibrosis (CF) is currently limited, and is a barrier to advancements in care and research for this population. In this proposal, we hypothesize that magnetic resonance imaging (MRI) of the lung and pulmonary circulation has the potential to serve as a sensitive and portable tool to monitor early CF lung disease, and that changes in pulmonary perfusion and/or structure can be correlated with peripheral biomarkers identified by metabolomics and proteomic methodology. The proposal couples advancements in MRI techniques with the emerging technologies of metabolomics and proteomics, linking new MR imaging to candidate and novel pathway analysis. We will examine three aspects of pulmonary blood flow (total and regional pulmonary perfusion, vascular resistance, and aortopulmonary collateral blood flow) compared with structural assessment of the lung by MRI and CT. These studies will be performed in CF and non-CF controls age 6 months - 3 years, with repeated measures in CF patients. Candidate metabolomic pathways that segregate CF from non-CF conditions (including oxidative status, purinergic signaling, and glucose metabolism) will be the focus of initial biomarker analysis, with advanced bioinformatic techniques applied to define novel relationships between the metabolome and imaging. (End of Abstract)