Using MRI to Observe Lung Changes in Infants With CF Compared to Infants Without CF
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Observational

Summary: 
      Our research is comparing the lungs of babies and young children with CF (cystic fibrosis) to
      those without CF. We are looking at the blood flow in the lungs to help doctors better
      understand how CF damages lungs and how to prevent this damage in the future. We will use MRI
      (Magnetic Resonance Imaging) and special blood tests as ways to understand early changes in
      the lungs of babies and young children with CF. We will look at the special blood tests to
      see if they can work as signals for the doctors to better understand when changes are
      happening in the lungs.

      For the babies with CF, we will compare MRI images of the lungs to their CT images (also
      sometimes called CAT scans or Computerized Tomography). We hope that this study will help us
      reduce the number of X-rays and CT scans children with CF might get in the future. Because
      MRI's do not use radiation, this could reduce the amount of radiation exposure that children
      with CF would get over their lifetime.
    

Detailed description: 
      Cystic fibrosis (CF) is a well characterized multi-organ disease producing mucus obstruction,
      chronic lung infection, inflammation, and oxidant stress. These processes result in airway
      damage, chronic pulmonary symptoms, and ultimately death in young adulthood. These processes
      are largely silent in the infant and toddler CF population, and ultimately result in lung
      damage and symptoms of CF. Detection and monitoring of lung disease in infants and toddlers
      with CF is currently limited, and is a major barrier to advancements in care and research for
      this population.

      This study will be performed in CF and non-CF controls age 6 months - 4.5 years, with
      repeated measures in CF patients over this window. We intend to examine new techniques to
      evaluate the lung of CF infants based on magnetic resonance imaging (MRI) that incorporates
      measurements of lung structure and blood flow. In the CF group, we will augment MRI images
      with CT images to determine structural relationships between MR and CT (a gold standard to
      assess lung structure in CF). We will correlate imaging data with core peripheral biomarkers
      of CF using an unbiased, metabolomic and proteomic-based approach. It is hoped that the
      results of this study will provide support for the use of MRI to monitor lung structure and
      blood flow in early CF lung disease, potentially providing a modality to monitor disease
      status independent of radiation exposure.

      We hypothesize that MRI of the lung and pulmonary circulation has the potential to serve as a
      sensitive and portable tool to monitor early CF lung disease. We will examine three
      functional 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.

      This proposal couples advancements in magnetic resonance imaging (MRI) techniques with the
      emerging technologies of metabolomics and proteomics, linking new MR imaging to candidate and
      novel pathway analysis. We will use the new technologies (metabolomics and proteomics -
      performed on peripheral blood samples) to determine if altered signaling pathways detected in
      the blood are related to changes in the lung. We hypothesize that changes in pulmonary
      perfusion and/or structure can be correlated with peripheral biomarkers identified by
      metabolomics and proteomic methodology.

      Candidate metabolomic pathways that have been shown to 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. Proteomics will serve a validating
      function, helping to assign enzyme pathways to metabolomics alterations.

      The study design includes 30 CF subjects divided into 2 age groups (6 to 12 month old and 24
      to 36 month old) who will receive chest CT and High Resolution CT (HRCT) at baseline and 12
      months later. They will be compared to 30 age matched non-CF subjects who will have one visit
      of MRI with contrast. The non-CF group only includes subjects scheduled for MRI for clinical
      reasons and will have an additional chest imaging at the end of their scheduled MRI. Both
      groups will have blood drawn to measure metabolomic and proteomic markers.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        CF infants 6 to 12 months or CF infants 24 to 36 months or non-CF controls between 6 months
        to 52 months scheduled for clinical MRI and willing to have contrast.
      
Biospecimen description: 
      serum
    
Keywords: Cystic Fibrosis; CF; MRI; vascularization; perfusion