Imaging of the human embryo with magnetic resonance imaging microscopy and high-resolution transvaginal 3-dimensional sonography: human embryology in the 21st century

Objective

This article illustrates early human development, demonstrated by magnetic resonance (MR) microscopy and computer graphics on human embryo specimens, and advanced 3-dimensional (3D) sonography in clinical obstetrics.

Study Design

Fixed human embryo specimens were imaged by MR microscopy coupled with computer graphics technology. Transvaginal 3D sonography was used to examine embryos in ongoing gestations and compare embryological findings.

Results

Advances in MR microscopy allowed detailed visualization of embryo specimens. Computational techniques allowed reconstruction of tomographic images to render them as 3D structures. High-resolution transvaginal 3D sonography produced images that demonstrated the neural tube from week 6; brain anatomy and vasculature from week 8; and craniofacial morphology and other structures from week 11.

Conclusion

MR microscopy is a novel technique that enables nondestructive, high-resolution imaging of embryo specimens. On the other hand, 3D sonoembryology allows detailed anatomical visualization in vivo and is the basis for the assessment of anomalies as well as human development.

Definition of the normal anatomy of the human embryo is essential to assess embryonic development and growth as well as to identify and diagnose congenital anomalies in early pregnancy. A major limitation to define, noninvasively, human embryonic anatomy has been the resolution of the tools available. The development of experimental magnetic resonance (MR) microscopy and its application to the study of embryos, coupled with the application of computer graphics, has allowed insights into early human development. On the other hand, the term “sonoembryology” was first coined in 1990 after the introduction of high-frequency transvaginal transducers in clinical obstetrics. Three-dimensional (3D) sonography performed with a transvaginal approach has expanded the depth of inquiry and allowed 3D sonoembryology.

A major limitation of embryology has been that it has been traditionally based in specimens obtained after embryonic death. Modern imaging techniques allow the definition of in vivo anatomy including visualization of the embryonic circulation and dynamic features that could not be characterized in fixed specimens.

In this article, we review the most recent knowledge acquired in embryology utilizing MR microscopy and illustrate the anatomical counterparts with 3D anatomy: 3D sonoembryology. The staging and description of age in traditional embryology is different from that used in obstetrics. Gestational age in obstetrics and maternal-fetal medicine is based on menstrual age rather than conceptual age. Embryology, instead, uses conceptual age. We have chosen to continue to use menstrual age because this is the parameter widely used in clinical medicine, however, with recent advances of 3D visualization in utero described in this article, readers are asked to be aware of the potential pitfalls of employing menstrual age.

Modern Embryology by MR Microscopy and Computer Graphics

The most widely used method for the classification of embryos is the Carnegie staging system. This method was developed at the world-renowned Carnegie Institute, which began collecting and classifying embryos in the early 1900s. An embryo is assigned a Carnegie stage (numbered from 1-23) based on its external morphological features. Age and size alone have been demonstrated to be of limited value in the classification of embryos. The difficulties in assigning age to an embryo after fixation derive from the effects of postmortem changes as well as the materials used for the preservation of specimens. Therefore, the Carnegie staging of human embryos is not dependent on the putative menstrual or embryonic age (which could be mistaken) or the size of the embryos (which could undergo embryonic growth retardation, or alternatively, fixation of postmortem artifacts) but on multiple morphologic features. It is assumed that the development of a discrete structure is a more reliable marker of the stage of embryonic development than size or putative age.

Recent advances in MR microscopic technology has made it possible to scan and visualize relatively small embryos, including those of mammals. We scanned >1400 human embryo specimens in the Kyoto Collection using a MR microscopy equipped with a 2.35-T superconducting magnet. The pulse sequence was a T1-weighted 3D gradient echo sequence (time to repeat = 100 milliseconds, time to echo = 8 milliseconds). Embryo specimens were images in test tubes (diameter = 13.5 mm) filled with 4% formaldehyde solution. Further details of the MR technology have been described elsewhere.

A detailed characterization of the central nervous system (CNS) at Carnegie stage 23 is illustrated by MR microscopy in Figure 1 . Figure 2 shows the remarkable change of the CNS that takes place between Carnegie stage 18 and 23. MR microscopy allows tomographic imaging of small structures, and the digitized data can be used for the purposes of 3D reconstruction. The initial difficulties of limited resolution and long sequences of MR imaging have been overcome with the developments of superparallel MR microscopy. Additionally, advances in computer graphic techniques combined with MR microscopy have been used to generate detailed 3D images of human embryos. Yamada et al have successfully constructed a series of 3D images of human embryos, based on the MR microscopy data of human embryo specimens in the Kyoto Collection ( Figures 3 and 4 ). The surface data of MR images were extracted using the MATLAB program (MathWorks, Natick, MA) and some cosmetic modification was given to diminish deformation and other postmortem changes. Computer graphic techniques have been invaluable to illustrate 3D anatomical structures and motion of structures during development ( Figures 5 and 6 ). In addition, Yamada et al have produced movies using these 3D images, which are of extraordinary value in understanding and visualizing development. This material can be obtained through the following World Wide Web site: http://mrw.interscience.wiley.com.easyaccess1.lib.cuhk.edu.hk/suppmat/1058-8388/suppmat/dvdy.20647.html or by contacting Kyoto University.