Phenotyping cardiac and structural birth defects in fetal and newborn mice.
Phenotyping cardiac and structural birth defects in fetal and newborn mice.
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DOI：
10.1002/bdr2.1048
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发表时间：
2017-06-01
影响因子：
2.1
通讯作者：
Lo CW
中科院分区：
文献类型：
--
作者：
Liu X;Kim AJ;Reynolds W;Wu Y;Lo CW
小鼠模型对于研究结构性出生缺陷的发育病因学和分子发病机制是非常宝贵的。虽然这已被用于研究广泛的出生缺陷，但小鼠对于先天性心脏病建模特别有价值，因为它们具有与人类相同的四腔心脏解剖结构。我们已经开发了使用非侵入性胎儿超声与微型计算机断层扫描（micro-CT）成像高通量表型小鼠先天性心脏病（CHD）和其他发育异常。我们显示了胎儿超声和微型CT成像诊断广泛的CHD的有效性。通过胎儿超声，可以进行纵向扫描以跟踪疾病发病机制的发育概况，提供二维（2D）成像的结构信息，以及彩色血流和频谱多普勒成像的血流动力学评估的功能数据。相比之下，通过显微CT成像，可以在死后快速进行虚拟尸检，不仅用于诊断CHD，还用于诊断其他结构性出生缺陷。为了验证CHD的诊断，我们进一步展示了一种新的组织学技术与episcopic共聚焦显微镜（ECM）的使用，以获得快速的3D重建，即使是最复杂的解剖缺陷的准确诊断。后一种组织学成像技术与超声和显微CT成像结合使用时，提供了成像方式的强大组合，这在满足未来功能基因组学时代对基因工程小鼠的高通量小鼠表型分析的加速需求方面将是非常宝贵的。
Mouse models are invaluable for investigating the developmental etiology and molecular pathogensis of structural birth defects. While this has been deployed for studying a wide spectrum of birth defects, mice are particularly valuable for modeling congenital heart disease, given they have the same four chamber cardiac anatomy as in humans. We have developed the use of noninvasive fetal ultrasound together with micro-computed tomography (micro-CT) imaging for high throughput phenotyping of mice for congenital heart defects (CHD) and other developmental anomalies. We showed the efficacy of fetal ultrasound and micro-CT imaging for diagnosis of a wide spectrum of CHD. With fetal ultrasound, longitundinal scans can be conducted to track the developmental profile of disease pathogenesis, providing both structural information with two-dimensional (2D) imaging, as well as functional data from hemodynamic assessments with color flow and spectral Dopper imaging. In contrast, with micro-CT imaging, virtual necropsies can be conducted rapidly postmortem for diagnosis of not only CHD, but also other structural birth defects. To validate the CHD diagnosis, we further showed the use of a novel histological technique with episcopic confocal microscopy (ECM) to obtain rapid 3D reconstructions for accurate diagnosis of even the most complex anatomical defect. The latter histological imaging technique when combined with the use of ultrasound and micro-CT imaging provides a powerful combination of imaging modalities that will be invaluable in meeting the accelerating demands for high throughput mouse phenotyping of genetically engineered mice in the coming age of functional genomics.