Treatment response of ethyl pyruvate in a mouse model of chronic obstructive pulmonary disease studied by hyperpolarized129Xe MRI.
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 hyperpolarized129Xe (HPXe) magnetic resonance imaging (MRI) strategy.



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.



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.



This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable129Xe MRI procedure. Magn Reson Med 78:721-729, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Atsuomi
A
Kimura
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yukiko
Y
Yamauchi
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Shota
S
Hodono
Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom.
Neil James
0000-0001-8358-394X
NJ
Stewart
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Osamu
O
Hosokawa
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yu
Y
Hagiwara
Research and Educational Unit of Leaders for Integrated Medical System, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
Hirohiko
H
Imai
Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Hideaki
H
Fujiwara
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000188:drug therapy; D011773:Pyruvates / Q000627:therapeutic use*; D014979:Xenon Isotopes / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D011773:Pyruvates; D014979:Xenon Isotopes; C046522:ethyl pyruvate
ethyl pyruvate; hyperpolarized 129Xe MRI; lung functional assessment; murine chronic obstructive pulmonary disease; treatment response