Treatment response of ethyl pyruvate in a mouse model of chronic obstructive pulmonary disease studied by hyperpolarized 129 Xe MRI

Magn Reson Med. 2017 Aug;78(2):721-729. doi: 10.1002/mrm.26458. Epub 2016 Sep 30.


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. © 2016 International Society for Magnetic Resonance in Medicine.

Keywords: ethyl pyruvate; hyperpolarized 129Xe MRI; lung functional assessment; murine chronic obstructive pulmonary disease; treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Pulmonary Disease, Chronic Obstructive* / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pyruvates / therapeutic use*
  • Xenon Isotopes / chemistry*


  • Anti-Inflammatory Agents
  • Pyruvates
  • Xenon Isotopes
  • ethyl pyruvate