Three-Dimensional Reconstruction and Morphologic Measurements of Human Embryonic Hearts: A New Diagnostic and Quantitative Method Applicable to Fetuses Younger than 13 Weeks of Gestation

Abstract

Improvements in the diagnosis of congenital malformations explain the increasing early termination of pregnancies. Before 13 weeks of gestation, an accurate in vivo anatomic diagnosis cannot currently be made in all fetuses with current imaging instrumentation. Anatomopathologic examinations remain the gold standard to make accurate diagnoses, although they reach limits between 9 and 13 weeks of gestation. We present the first results of a methodology that can be applied routinely, using standard histologic section, thus enabling the reconstruction, visual estimate, and quantitative analysis of 13-week human embryonic cardiac structures. The cardiac blocks were fixed, embedded in paraffin, and entirely sliced by a microtome. One of 10 slices was topographically colored and digitized on an optical microscope. Cardiac volume was recovered by semiautomatic realignment of the sections. Another semiautomatic procedure allowed extracting and labeling of cardiac structures from the volume. Structures were studied with display tools, which disclosed the internal and external cardiac components and enabled determination of size, thickness, and precise positioning of ventricles, atria, and large vessels. This pilot study confirmed that a new 3-dimensional reconstruction and visualization method enables accurate diagnoses, including in embryos younger than 13 weeks. Its implementation at earlier stages of embryogenesis will provide a clearer view of cardiac development.