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)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-F (S1))
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Banks-Schlegel, Susan P
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Cincinnati Children's Hospital Medical Center
United States
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Pennati, Francesca; Roach, David J; Clancy, John P et al. (2018) Assessment of pulmonary structure-function relationships in young children and adolescents with cystic fibrosis by multivolume proton-MRI and CT. J Magn Reson Imaging 48:531-542
Thomen, Robert P; Walkup, Laura L; Roach, David J et al. (2017) Hyperpolarized129Xe for investigation of mild cystic fibrosis lung disease in pediatric patients. J Cyst Fibros 16:275-282
Muhlebach, Marianne S; Clancy, J P; Heltshe, Sonya L et al. (2016) Biomarkers for cystic fibrosis drug development. J Cyst Fibros 15:714-723
Walkup, Laura L; Thomen, Robert P; Akinyi, Teckla G et al. (2016) Feasibility, tolerability and safety of pediatric hyperpolarized (129)Xe magnetic resonance imaging in healthy volunteers and children with cystic fibrosis. Pediatr Radiol 46:1651-1662
Spielberg, David R; Clancy, John P (2016) Cystic Fibrosis and Its Management Through Established and Emerging Therapies. Annu Rev Genomics Hum Genet 17:155-75
Kramer, Elizabeth L; Clancy, John P (2016) CFTR Modulator Therapies in Pediatric Cystic Fibrosis: Focus on Ivacaftor. Expert Opin Orphan Drugs 4:1033-1042
Roach, David J; Crémillieux, Yannick; Fleck, Robert J et al. (2016) Ultrashort Echo-Time Magnetic Resonance Imaging Is a Sensitive Method for the Evaluation of Early Cystic Fibrosis Lung Disease. Ann Am Thorac Soc 13:1923-1931
Kotha, Kavitha; Szczesniak, Rhonda D; Naren, Anjaparavanda P et al. (2015) Concentration of fractional excretion of nitric oxide (FENO): A potential airway biomarker of restored CFTR function. J Cyst Fibros 14:733-40
Ehsan, Zarmina; Clancy, John P (2015) Management of Pseudomonas aeruginosa infection in cystic fibrosis patients using inhaled antibiotics with a focus on nebulized liposomal amikacin. Future Microbiol 10:1901-12
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

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