Semi-Automatic Classification of Skeletal Morphology in Genetically Altered Mice Using Flat-Panel Volume Computed Tomography 英文参考文献.docVIP

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Semi-Automatic Classification of Skeletal Morphology in Genetically Altered Mice Using Flat-Panel Volume Computed Tomography 英文参考文献.doc

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Semi-Automatic Classification of Skeletal Morphology in Genetically Altered Mice Using Flat-Panel Volume Computed Tomography 英文参考文献

Semi-AutomaticClassificationofSkeletal MorphologyinGeneticallyAlteredMice UsingFlat-PanelVolumeComputed Tomography Christian Dullin1*,Jeannine Missbach-Guentner1,2,Wolfgang F.Vogel3,Eckhardt Grabbe1,Frauke Alves2 1Department ofDiagnosticRadiology,Georg-August-University,Go¨ttingen,Germany,2DepartmentofHematologyandOncology,Georg-August-University,Go¨ttingen, Germany,3DepartmentofLaboratoryMedicineandPathobiology,UniversityofToronto,Toronto,Ontario,Canada Rapidprogressinexploringthehumanandmousegenomehasresultedinthegenerationofamultitudeofmouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT) for high-resolution 3-D imaging and developedanalgorithmwithacomputationalintelligencesystem.First,wetestedtheaccuracyandreliabilityofthis approachbyimagingdiscoidindomainreceptor2-(DDR2-)deficientmice,whichdisplaydistinctskullabnormalitiesas shownbycomparativelandmark-basedanalysis.High-contrastfpVCTdataoftheskullwith200lmisotropicresolution and 8-s scan time allowed segmentation and computation of significant shape features as well as visualization of morphologicaldifferences.Theapplicationofatrainedartificialneuronalnetworktothesedatasetspermittedasemi- automaticandhighlyaccuratephenotypeclassificationofDDR2-deficientcomparedtoC57BL/6wild-typemice.Even heterozygous DDR2 mice with only subtle phenotypic alterations were correctly determined by fpVCT imaging and identifiedasanewclass.Inaddition,wesuccessfullyappliedthealgorithmtoclassifyknockoutmicelackingtheDDR1 genewithnoapparentskulldeformities.Thus,thisnewmethodseemstobeapotentialtooltoidentifynovelmouse phenotypeswithskullchangesfromtransgenicandknockoutmiceonthebasisofrandommutagenesisaswellasfrom geneticmodels.Howeverforthispurpose,newneuronalnetworkshavetobecreatedandt