title: Microcomputed tomography provides high accuracy congenital heart disease diagnosis in neonatal and fetal mice.
abstract: BACKGROUND
  Mice are well suited for modeling human congenital heart disease (CHD), given their 4-chamber cardiac anatomy. However, mice with CHD invariably die prenatally/neonatally, causing CHD phenotypes to be missed. Therefore, we investigated the efficacy of noninvasive microcomputed tomography (micro-CT) to screen for CHD in stillborn/fetal mice. These studies were performed using chemically mutagenized mice expected to be enriched for birth defects, including CHD.
  
  
  RESULTS
  Stillborn/fetal mice obtained from the breeding of N-ethyl-N-nitrosourea mutagenized mice were formalin-fixed and stained with iodine, then micro-CT scanned. Those diagnosed with CHD and some CHD-negative pups were necropsied. A subset of these were further analyzed by histopathology to confirm the CHD/no-CHD diagnosis. Micro-CT scanning of 2105 fetal/newborn mice revealed an abundance of ventricular septal defects (n=307). Overall, we observed an accuracy of 89.8% for ventricular septal defect diagnosis. Outflow tract anomalies identified by micro-CT included double outlet right ventricle (n=36), transposition of the great arteries (n=14), and persistent truncus arteriosus (n=3). These were diagnosed with a 97.4% accuracy. Aortic arch anomalies also were readily detected with an overall 99.6% accuracy. This included right aortic arch (n=28) and coarctation/interrupted aortic arch (n=12). Also detected by micro-CT were atrioventricular septal defects (n=22), tricuspid hypoplasia/atresia (n=13), and coronary artery fistulas (n=16). They yielded accuracies of 98.9%, 100%, and 97.8%, respectively.
  
  
  CONCLUSIONS
  Contrast enhanced micro-CT imaging in neonatal/fetal mice can reliably detect a wide spectrum of CHD. We conclude that micro-CT imaging can be used for routine rapid assessments of structural heart defects in fetal/newborn mice.
authors.affiliation: Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kim
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.forename: William A
authors.initials: WA
authors.lastname: Devine
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ramirez
authors.forename: Shane J
authors.initials: SJ
authors.lastname: Anderton
authors.forename: Li Yin
authors.initials: LY
authors.lastname: Wong
authors.forename: Fahim
authors.initials: F
authors.lastname: Faruque
authors.forename: George C
authors.initials: GC
authors.lastname: Gabriel
authors.forename: Wendy
authors.initials: W
authors.lastname: Chung
authors.forename: Linda
authors.initials: L
authors.lastname: Leatherbury
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003287:Contrast Media; D004195:Disease Models, Animal; D005318:Fetal Heart / Q000002:abnormalities* / Q000000981:diagnostic imaging* / Q000473:pathology; D005838:Genotype; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015588:Observer Variation; D010641:Phenotype; D011237:Predictive Value of Tests; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media
keywords: ENU; X-ray microtomography; congenital heart disease; mouse mutagenesis screen