Development and application of an innovative pulmonary functional diagnostic system using hyperpolarized noble gas MRI aiming at complete polarization

2019 Fiscal Year Final Research Report

• Project/Area Number: 15H03006
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Osaka University
• Principal Investigator: Kimura Atsuomi 大阪大学, 医学系研究科, 准教授 (70303972)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Keywords: 完全偏極キセノン / 肺機能診断 / 難治性肺疾患 / 新薬探索 / ピルビン酸エチル

Outline of Final Research Achievements

We succeeded in improving the MRI sensitivity of Xe by introducing a newly developed high-power, narrow-band laser to our home-built continuous-flow type apparatus for producing hyperpolarized xenon (HPXe), which achieved a maximum polarization level of 84%.. Based on this apparatus, a unique HPXe MRI pulmonary functional diagnostic system for small animals was constructed. Using this system, we performed preclinical evaluation for refractory lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis, and found ethyl pyruvate (EP) as a novel drug candidate. Furthermore, the mechanism of EP efficacy was investigated and suggested to be associated with down-regulating the expression of HMGB1, which is one of damage-associated molecular patterns, through inhibition of NF-kB, leading to wound healing of alveolar tissue and improvement of lung function.

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Academic Significance and Societal Importance of the Research Achievements

準完全偏極Xe-MRIは肺機能診断の進展に大きく貢献するばかりでなく、慢性閉塞性肺疾患（COPD）や肺線維症など難治性肺疾患の新たな薬物治療戦略の確立に資する。これまで、これらの疾患では有効な薬物の開発が困難であったが、これは肺機能評価系の構築が難しかったことによる。これに対して、呼吸によって肺に取り込まれた超偏極Xe の特徴的な動態を解析する事でユニークな肺機能評価法を提供できた。また、本手法が肺疾患の前臨床評価に有効である事を実証し、新薬シードとしてピルビン酸エチルを見出した。本研究によって、診断の高精細化および新たな治療法の開発を図るうえで意義深い成果を残すことができた。