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Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis
Authors:Marcus J. Couch  Matthew S. Fox  Chris Viel  Gowtham Gajawada  Tao Li  Alexei V. Ouriadov  Mitchell S. Albert
Affiliation:1. Lakehead University, Thunder Bay, Ontario, Canada;2. Thunder Bay Regional Research Institute, Thunder Bay, Ontario, Canada;3. Robarts Research Institute, Western University, London, Ontario, Canada;4. Department of Medical Biophysics, Western University, London, Ontario, Canada
Abstract:The purpose of this study was to extend established methods for fractional ventilation mapping using 19F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. 19F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O2. Fractional ventilation maps were obtained using a wash‐out approach, by switching the breathing mixture to pure O2, and acquiring images following each successive wash‐out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS‐instilled rats and 0.19 ± 0.03 for bleomycin‐instilled rats. Bleomycin‐instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS‐instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was ?0.005 ± 0.008 cm?1 for control rats, 0.013 ± 0.005 cm?1 for LPS‐instilled rats and 0.009 ± 0.018 cm?1 for bleomycin‐instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS‐instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS‐ and bleomycin‐instilled rats showed the opposite trend. Histology confirmed that LPS‐instilled rats had a significantly elevated alveolar wall thickness, while bleomycin‐instilled rats showed signs of substantial fibrosis. Overall, 19F MRI may be able to detect the effects of pulmonary inflammation and fibrosis using a simple and inexpensive imaging approach that can potentially be translated to humans. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords:19F MRI  inert fluorinated gas MRI  fractional ventilation mapping  ventilation gradients  inflammation  lipopolysaccharide  bleomycin
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