Microcomputed tomography provides high accuracy congenital heart disease diagnosis in neonatal and fetal mice

Circ Cardiovasc Imaging. 2013 Jul;6(4):551-9. doi: 10.1161/CIRCIMAGING.113.000279. Epub 2013 Jun 12.


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.

Methods and 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.

Keywords: ENU; X-ray microtomography; congenital heart disease; mouse mutagenesis screen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Contrast Media
  • Disease Models, Animal
  • Fetal Heart / abnormalities*
  • Fetal Heart / diagnostic imaging*
  • Fetal Heart / pathology
  • Genotype
  • Gestational Age
  • Heart Defects, Congenital / diagnostic imaging*
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Observer Variation
  • Phenotype
  • Predictive Value of Tests
  • Prenatal Diagnosis / methods*
  • Reproducibility of Results
  • X-Ray Microtomography*


  • Contrast Media