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.

Public Health Relevance

Cystic fibrosis (CF) causes progressive lung damage that begins in infancy. New tools are needed to monitor early lung disease, and to bring new therapies to infants and toddlers with CF. In this proposal, we will use new imaging and blood-based technologies to improve our ability to monitor lung status in young children with CF.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZHL1)
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Smith, Robert A
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Sun, Hongtao; Harris, William T; Kortyka, Stephanie et al. (2014) Tgf-beta downregulation of distinct chloride channels in cystic fibrosis-affected epithelia. PLoS One 9:e106842
Fleck, Robert; McPhail, Gary; Szczesniak, Rhonda et al. (2013) Aortopulmonary collateral flow in cystic fibrosis assessed with phase-contrast MRI. Pediatr Radiol 43:1279-86