title: Quantitative assessment of lung microstructure in healthy mice using an MR-based 3He lung morphometry technique.
abstract: The recently developed technique of lung morphometry using hyperpolarized (3)He diffusion magnetic resonance (MR) (Yablonskiy DA, Sukstanskii AL, Woods JC, Gierada DS, Quirk JD, Hogg JC, Cooper JD, Conradi MS. J Appl Physiol 107: 1258-1265, 2009) permits in vivo study of lung microstructure at the alveolar level. Originally proposed for human lungs, it also has the potential to study small animals. The technique relies on theoretical developments in the area of gas diffusion in lungs linking the diffusion attenuated MR signal to the lung microstructure. To adapt this technique to small animals, certain modifications in MR protocol and data analysis are required, reflecting the smaller size of mouse alveoli and acinar airways. This is the subject of the present paper. Herein, we established empirical relationships relating diffusion measurements to geometrical parameters of lung acinar airways with dimensions typical for mice and rats by using simulations of diffusion in the airways. We have also adjusted the MR protocol to acquire data with much shorter diffusion times compared with humans to accommodate the substantially smaller acinar airway length. We apply this technique to study mouse lungs ex vivo. Our MR-based measurements yield mean values of lung surface-to-volume ratio of 670 cm(-1), alveolar density of 3,200 per mm(3), alveolar depth of 55 μm, and mean chord length of 62 μm, all consistent with published data obtained histologically in mice by unbiased methods. The proposed technique can be used for in vivo experiments, opening a door for longitudinal studies of lung morphometry in mice and other small animals.
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: E
authors.initials: E
authors.lastname: Osmanagic
authors.forename: A L
authors.initials: AL
authors.lastname: Sukstanskii
authors.forename: J D
authors.initials: JD
authors.lastname: Quirk
authors.forename: J C
authors.initials: JC
authors.lastname: Woods
authors.forename: R A
authors.initials: RA
authors.lastname: Pierce
authors.forename: M S
authors.initials: MS
authors.lastname: Conradi
authors.forename: E R
authors.initials: ER
authors.lastname: Weibel
authors.forename: D A
authors.initials: DA
authors.lastname: Yablonskiy
mesh_terms: D000818:Animals; D000886:Anthropometry / Q000379:methods*; D049628:Body Size; D055745:Bronchioles / Q000033:anatomy & histology; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D005740:Gases; D006371:Helium; D008168:Lung / Q000033:anatomy & histology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D011650:Pulmonary Alveoli / Q000033:anatomy & histology
chemical_list: D005740:Gases; D006371:Helium
references.citation: Eur Respir J. 2004 Oct;24(4):524-32
references.pmid: 15459128
references.citation: J Appl Physiol (1985). 1987 May;62(5):1878-87
references.pmid: 3597262
references.citation: Anat Rec (Hoboken). 2009 Jan;292(1):113-22
references.pmid: 19115381
references.citation: J Appl Physiol (1985). 2010 Feb;108(2):412-21
references.pmid: 19959763
references.citation: Phys Rev A. 1995 Jul;52(1):862-865
references.pmid: 9912313
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11478-81
references.pmid: 11027348
references.citation: J Appl Physiol (1985). 2009 Oct;107(4):1258-65
references.pmid: 19661452
references.citation: Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
references.pmid: 20130146
references.citation: J Appl Physiol (1985). 2007 Mar;102(3):1273-80
references.pmid: 17110518
references.citation: Respir Res. 2007 Oct 03;8:70
references.pmid: 17915009
references.citation: Magn Reson Med. 2000 Aug;44(2):174-9
references.pmid: 10918314
references.citation: J Appl Physiol (1985). 2007 Jan;102(1):477-84
references.pmid: 16873601
references.citation: Magn Reson Med. 2006 Dec;56(6):1293-300
references.pmid: 17058206
references.citation: Radiology. 2002 Jan;222(1):252-60
references.pmid: 11756734
references.citation: Am J Pathol. 1945 Sep;21(5):889-903
references.pmid: 19970843
references.citation: J Magn Reson. 2009 Mar;197(1):56-62
references.pmid: 19128992
references.citation: J Magn Reson. 2008 Feb;190(2):200-10
references.pmid: 18037313
references.citation: Phys Rev A. 1990 Jun 1;41(11):6063-6070
references.pmid: 9903009
references.citation: J Magn Reson. 2007 Oct;188(2):357-66
references.pmid: 17827044
references.citation: Am J Physiol Lung Cell Mol Physiol. 2009 Jan;296(1):L57-70
references.pmid: 18952756
references.citation: J Appl Physiol (1985). 2008 Oct;105(4):1291-300
references.pmid: 18719237
references.citation: Swiss Med Wkly. 2009 Jul 11;139(27-28):375-86
references.pmid: 19629765
references.citation: Anat Rec. 1988 Apr;220(4):401-14
references.pmid: 3382030
references.citation: J Appl Physiol (1985). 2008 Dec;105(6):1984-5; author reply 1986-7
references.pmid: 19140250
references.citation: Nature. 1994 Jul 21;370(6486):199-201
references.pmid: 8028666
references.citation: Respir Res. 2003;4:4
references.pmid: 12783622
references.citation: J Clin Invest. 2008 Aug;118(8):2771-84
references.pmid: 18654661
references.citation: Ann Biomed Eng. 2008 Dec;36(12):2111-20
references.pmid: 18633711
references.citation: Magn Reson Med. 1995 Feb;33(2):271-5
references.pmid: 7707920
references.citation: J Magn Reson Imaging. 2007 Mar;25(3):488-94
references.pmid: 17279537
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3111-6
references.pmid: 11867733
references.citation: Eur Respir J. 2003 Jul;22(1):14-9
references.pmid: 12882445
references.citation: Respir Physiol Neurobiol. 2005 Aug 25;148(1-2):23-42
references.pmid: 15967737
references.citation: J Appl Physiol (1985). 2004 May;96(5):1658-64
references.pmid: 15075308
references.citation: Am J Anat. 1987 Oct;180(2):143-55
references.pmid: 3673919