title: Validation of noninvasive morphological and diffusion imaging in mouse emphysema by micro-computed tomography and hyperpolarized (129)Xe magnetic resonance imaging.
abstract: Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized (129)Xe MRI, which can evaluate gas exchange between the alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice, and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease of the fD value in low-density areas with micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.
authors.affiliation: 1 Department of Respiratory Medicine, Allergy, and Rheumatic Diseases, Graduate School of Medicine.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tetsumoto
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Imai
authors.forename: Atsuomi
authors.initials: A
authors.lastname: Kimura
authors.forename: Yingji
authors.initials: Y
authors.lastname: Jin
authors.forename: Kaori
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeda
authors.forename: Hanako
authors.initials: H
authors.lastname: Kuhara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsujino
authors.forename: Takeo
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shigeta
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kondo
authors.forename: Mari
authors.initials: M
authors.lastname: Ito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Minami
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Hirata
authors.forename: Ryo
authors.initials: R
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kohmo
authors.forename: Izumi
authors.initials: I
authors.lastname: Nagatomo
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.forename: Isao
authors.initials: I
authors.lastname: Tachibana
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Toru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000000981:diagnostic imaging* / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000473:pathology*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D014979:Xenon Isotopes / Q000032:analysis*
chemical_list: D014979:Xenon Isotopes