Atsuomi Kimura1, Yukiko Yamauchi1, Shota Hodono1, Neil James Stewart2, Osamu Hosokawa1, Yu Hagiwara1, Hirohiko Imai3, Hideaki Fujiwara1. 1. Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan. 2. Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom. 3. Research and Educational Unit of Leaders for Integrated Medical System, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
Abstract
PURPOSE: The purpose of this work was to investigate disease progression and treatment response in a murine model of chronic obstructive pulmonary disease (COPD) using a preclinical hyperpolarized 129 Xe (HPXe) magnetic resonance imaging (MRI) strategy. METHODS: COPD phenotypes were induced in 32 mice by 10 weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe MRI was performed to monitor changes in pulmonary function during disease progression and pharmacological therapy. RESULTS: HPXe metrics of fractional ventilation and gas-exchange function were significantly reduced after 6 weeks of CS and LPS exposure compared to sham-instilled mice administered with saline (P < 0.05). After this observation, EP administration was started in 16 of the 32 mice and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar level as in sham-instilled mice (P < 0.01). Histological analysis showed significant alveolar tissue destruction in the COPD group, but relatively normal alveolar structure in the EP and sham-instilled groups. CONCLUSION: This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable 129 Xe MRI procedure. Magn Reson Med 78:721-729, 2017.
PURPOSE: The purpose of this work was to investigate disease progression and treatment response in a murine model of chronic obstructive pulmonary disease (COPD) using a preclinical hyperpolarized 129 Xe (HPXe) magnetic resonance imaging (MRI) strategy. METHODS: COPD phenotypes were induced in 32 mice by 10 weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe MRI was performed to monitor changes in pulmonary function during disease progression and pharmacological therapy. RESULTS: HPXe metrics of fractional ventilation and gas-exchange function were significantly reduced after 6 weeks of CS and LPS exposure compared to sham-instilled mice administered with saline (P < 0.05). After this observation, EP administration was started in 16 of the 32 mice and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar level as in sham-instilled mice (P < 0.01). Histological analysis showed significant alveolar tissue destruction in the COPD group, but relatively normal alveolar structure in the EP and sham-instilled groups. CONCLUSION: This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable 129 Xe MRI procedure. Magn Reson Med 78:721-729, 2017.