Human Cardiac Development in the First Trimester A High-Resolution Magnetic Resonance Imaging and Episcopic Fluorescence Image Capture Atlas
Human Cardiac Development in the First Trimester A High-Resolution Magnetic Resonance Imaging and Episcopic Fluorescence Image Capture Atlas
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DOI：
10.1161/circulationaha.108.796698
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发表时间：
2009-07-28
期刊：
影响因子：
37.8
通讯作者：
Lo, Cecilia W.
中科院分区：
文献类型：
--
作者：
Dhanantwari, Preeta;Lee, Elaine;Lo, Cecilia W.
随着医学成像的快速发展，人类先天性心脏病的胎儿诊断现在在怀孕早期从技术上来说是可行的。尽管希波克拉底在公元前300年至公元前400年记录了第一批人类胚胎学研究，但目前对怀孕前三个月正常人类心脏发育的了解仍然有限。1886年，希斯博士的两篇文章描述了在解剖年轻人类胚胎的基础上心脏的发育。制作了徒手蜡模型，展示了外部发育解剖结构。直到20世纪初，许多其他研究人员都在使用这些蜡板重建方法。1随后，连续的人类胚胎组织切片被用于进一步研究人类心脏的发育。2-6通过对人类胚胎的组织切片和按比例复制的分析，Grant2在66⁄7周(卡内基阶段[CS]14)的发育心脏中显示出大的垫层，在91⁄7周(CS 22)显示出分离的房室(AV)瓣膜。8周末(CS8)，观察到分离的主动脉和肺流出。ORTS-Llorca et AL5使用人类胚胎横切面的三维(3D)重建来定义动脉干的发育，并描述了14至16 mm胚胎中动脉干分离的完成，相当于估计胎龄(EGA)为8周(CS18)。考虑到与心腔形成、流入/流出道和瓣膜形态发生相关的复杂组织重建，切片平面往往限制了可以收集到的关于胚胎心脏发育结构的信息。这些技术限制，再加上对人类胚胎标本的有限获取，意味着我们对人类胚胎早期心脏发育的大部分理解都是从模型生物的研究中推断出来的。7-10由于发育时间和心血管解剖的变异可能存在物种差异，人类胚胎心脏正常发育的特征对于早期先天性心脏病的临床评估和诊断是必要的。随着医疗技术的进步，这将变得越来越重要，因为医学技术的进步允许更早地获得早期胚胎心脏成像和宫内干预。最近的研究表明，使用磁共振成像(MRI)来获取关于人类胚胎组织结构的信息是可行的。可以对MRI数据进行数字化切除，以便在任何方向上查看标本，并且可以轻松获得3D效果图。同样，表观荧光图像捕获(EFIC)是一种新的组织成像技术，它提供了注册的二维(2D)图像堆栈，可以在任意平面上切除并快速进行3D渲染。10通过EFIC成像，组织被石蜡包埋，并用雪橇切片机切割。捕获块面上的组织自体荧光，并用于生成具有比MRI更好的图像分辨率的样本的配准序列2D图像。通过MRI或EFIC成像获得的数据可以很容易地以数字方式切除或在3D中重建，以便于分析发育中的胚胎心脏的复杂形态变化。以这种方式，每个胚胎中的发育心脏可以被完整地分析，而不会因为切片平面而导致信息损失。
With rapid advances in medical imaging, fetal diagnosis of human congenital heart disease is now technically feasible in the first trimester. Although the first human embryological studies were recorded by Hippocrates in 300 to 400 BC, present-day knowledge of normal human cardiac development in the first trimester is still limited. In 1886, 2 articles by Dr His described the development of the heart on the basis of dissections of young human embryos. Free-hand wax models were made that illustrated the external developmental anatomy. These wax plate reconstruction methods were used by many other investigators until the early 1900s. 1 Subsequently, serial histological sections of human embryos have been used to further investigate human cardiac development. 2–6 Using an analysis of histological sections and scaled reproductions of human embryos, Grant2 showed a large cushion in the developing heart at 66⁄ 7 weeks (Carnegie stage [CS] 14) and separate atrioventricular (AV) valves at 91⁄ 7 weeks (CS 22). At the end of 8 weeks (CS 8), separate aortic and pulmonary outflows were observed. Orts-Llorca et al5 used 3-dimensional (3D) reconstructions of transverse sections of human embryos to define the development of the truncus arteriosus and described completion of septation of the truncus arteriosus in 14-to 16-mm embryos, equivalent to an estimated gestational age (EGA) of 8 weeks (CS 18). Given the complex tissue remodeling associated with cardiac chamber formation and inflow/outflow tract and valvular morphogenesis, the plane of sectioning often limited the information that can be gathered on developing structures in the embryonic heart. These technical limitations, in conjunction with limited access to human embryo specimens, have meant that much of our understanding of early cardiac development in the human embryo is extrapolated from studies in model organisms. 7–10 With possible species differences in developmental timing and variation in cardiovascular anatomy, characterization of normal cardiac development in human embryos is necessary for clinical evaluation and diagnosis of congenital heart disease in the first trimester.This will be increasingly important as improvements in medical technology allow earlier access to first-trimester human fetal cardiac imaging and in utero intervention. Recent studies have shown the feasibility of using magnetic resonance imaging (MRI) to obtain information on human embryo tissue structure. 11, 12 MRI data can be digitally resectioned for viewing of the specimen in any orientation, and 3D renderings can be obtained with ease. Similarly, episcopic fluorescence image capture (EFIC), a novel histological imaging technique, provides registered 2-dimensional (2D) image stacks that can be resectioned in arbitrary planes and rapidly 3D rendered. 10 With EFIC imaging, tissue is embedded in paraffin and cut with a sledge microtome. Tissue autofluorescence at the block face is captured and used to generate registered serial 2D images of the specimen with better image resolution than MRI. Data obtained by MRI or EFIC imaging can be easily resectioned digitally or reconstructed in 3D to facilitate the analysis of complex morphological changes in the developing embryonic heart. In this manner, the developing heart in every embryo can be analyzed in its entirety with no loss of information resulting from the plane of sectioning.