Schneider Jürgen E, Bamforth Simon D, Farthing Cassandra R, Clarke Kieran, Neubauer Stefan, Bhattacharya Shoumo
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.
J Mol Cell Cardiol. 2003 Feb;35(2):217-22. doi: 10.1016/s0022-2828(02)00291-2.
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.
小鼠胚胎心脏的发育畸形通常通过组织切片进行研究。这种方法速度慢、劳动强度大，并且会导致三维（3D）信息的丢失。胚胎的磁共振研究通常使用自旋回波序列，采集时间较长（>36小时）或灌注造影剂以提高分辨率和对比度。这在技术上很困难，并且需要大量的操作员时间。我们使用具有T(1)加权的快速扰相3D梯度回波序列，在无人值守的情况下进行了不到9小时的过夜扫描，对多聚甲醛固定的胚胎进行成像。在野生型胚胎中，我们可视化了正常的心脏结构，包括心腔、室间隔、原发和继发房间隔、瓣膜、上腔静脉和下腔静脉、主动脉、肺动脉和动脉导管。在缺乏Cited2（正常心脏发育所需的转录共激活因子）的胚胎中，我们发现了心脏畸形，包括房间隔和室间隔缺损、圆锥干畸形和主动脉弓畸形。我们使用轮廓识别和表面渲染计算机软件生成了正常和突变心脏的3D重建。这些畸形通过组织切片得到了证实。我们的数据表明，快速梯度回波序列磁共振成像可用于快速准确地识别转基因和突变小鼠胚胎中的复杂心血管畸形。
