Rapid identification and 3D reconstruction of complex cardiac malformations in transgenic mouse embryos using fast gradient echo sequence magnetic resonance imaging.
Developmental malformations of the heart in mouse embryos are commonly studied by histological sectioning. This is slow, labour intensive, and results in the loss of three-dimensional (3D) information. Magnetic resonance studies of embryos typically use spin-echo sequences, using prolonged acquisition times (>36 h) or perfusion with contrast agents to enhance resolution and contrast. This is technically difficult, and requires significant amounts of operator time. We imaged paraformaldehyde fixed embryos using a fast spoiled 3D gradient echo sequence with T(1)-weighting, in unattended overnight runs of less than 9 h. In wild-type embryos, we visualised normal cardiac structures, including cardiac chambers, the ventricular septum, primary and secondary atrial septa, valves, superior and inferior vena cava, aorta, pulmonary artery, and ductus arteriosus. In embryos lacking Cited2 (a transcriptional co-activator required for normal heart development), we identified cardiac malformations including atrial and ventricular septal defects, cono-truncal defects, and aortic arch malformations. We generated 3D reconstructions of normal and mutant hearts using contour identification and surface rendering computer software. The malformations were confirmed by histological sectioning. Our data indicate that fast gradient echo sequence magnetic resonance imaging can be used to rapidly and accurately identify complex cardiovascular malformations in transgenic and mutant mouse embryos.
Schneider
Jürgen E
JE
Department of Cardiovascular Medicine, University of Oxford, British Heart Foundation Molecular Cardiology Laboratory, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Bamforth
Simon D
SD
Farthing
Cassandra R
CR
Clarke
Kieran
K
Neubauer
Stefan
S
Bhattacharya
Shoumo
S
D000818:Animals; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000473:pathology; D006330:Heart Defects, Congenital / Q000175:diagnosis*; D006344:Heart Septal Defects, Atrial / Q000175:diagnosis; D006345:Heart Septal Defects, Ventricular / Q000175:diagnosis; D006579:Heterozygote; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012097:Repressor Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics
C110087:Cited2 protein, mouse; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators