Quantification of Lung Fibrosis and Emphysema in Mice Using Automated Micro-Computed Tomography 英文参考文献.docVIP

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Quantification of Lung Fibrosis and Emphysema in Mice Using Automated Micro-Computed Tomography 英文参考文献.doc

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Quantification of Lung Fibrosis and Emphysema in Mice Using Automated Micro-Computed Tomography 英文参考文献

QuantificationofLungFibrosisandEmphysemainMice UsingAutomatedMicro-ComputedTomography EllenDeLanghe1,2*,GreetjeVandeVelde3,JeroenHostens4,UweHimmelreich3,BenoitNemery5, FrankP.Luyten1,2,JeroenVanoirbeek5.,RikJ.Lories1,2. 1LaboratoryforSkeletalDevelopmentandJointDisorders,DepartmentofDevelopmentandRegeneration,KULeuven,Leuven,Belgium,2DepartmentofRheumatology, UniversityHospitalsLeuven,Leuven,Belgium,3BiomedicalNMRUnit/MoSAIC,DepartmentofImagingandPathology,KULeuven,Leuven,Belgium,4SkyScan,Kontich, Belgium,5ResearchUnitofLungToxicology,DepartmentofPublicHealth,KULeuven,Leuven,Belgium Abstract Background: Invivo high-resolutionmicro-computed tomography allowsforlongitudinal image-basedmeasurements in animalmodels oflungdisease.Thecombinationofrepetitivehighresolutionimagingwithfullyautomatedquantitative imageanalysisinmousemodelsoflungfibrosislungbenefitspreclinicalresearch.Thisstudyaimedtodevelopandvalidate suchanautomatedmicro-computedtomographyanalysisalgorithmforquantificationofaeratedlungvolumeinmice;an indicatorofpulmonaryfibrosisandemphysemaseverity. Methodology:Micereceivedanintratrachealinstillationofbleomycin(n=8),elastase(0.25Uelastasen=9,0.5Uelastase n=8) or saline control (n=6 for fibrosis, n=5 for emphysema). A subset of mice was scanned without intervention, to evaluatepotentialradiation-inducedtoxicity(n=4).Somebleomycin-instilledmiceweretreatedwithimatinibforproofof concept (n=8). Mice were scanned weekly, until four weeks after induction, when they underwent pulmonary function testing,lunghistologyandcollagenquantification.Aeratedlungvolumeswerecalculatedwithourautomatedalgorithm. PrincipalFindings:Ourautomatedimage-basedaeratedlungvolumequantificationmethodisreproduciblewithlowintra- subject variability. Bleomycin-treated mice had significantly lower scan-derived aerated lung volumes, compared to controls.Aeratedlungvolumecorrelatedwiththehistopathologicalfibrosisscoreandtotallungcollagencontent.Inversely, a dose-dependent increase in lung volume