Investigating the developmental processes of the human fetal heart is a
challenging task. Few reports describe the morphological features during the first stage
of heart maturation and consecutive developmental periods after cardiogenesis.
Reasons for this include the difficulty of collecting suitable samples and the limitations
of investigating modalities. This research was proposed to clarify the detailed
morphological features of normal human fetal hearts in early-stage maturation, using
post-mortem samples. These samples were analysed using high-resolution episcopic
microscopy (HREM), and compared with the latest clinical imaging taken by 3D fetal
echocardiography and compared with mouse samples.
HREM, a newly-developed high-quality image modality, produces a computerbased
3D reconstruction which enables us to visualize detailed spatial structures of
small specimens. HREM includes several procedural steps, which may affect the
histological or morphological structures of samples, so I explored the potential effects.
I found 12% shrinkage due to dehydration and polymerization. Therefore, while the
general appearance of 3D reconstructed images looked identical to the pictures of the
original heart samples, it is important to consider the effects of shrinkage when
interpreting the morphological assessment by HREM.
Normal human fetal hearts from the 9th to 11th weeks of postmenstrual
gestation demonstrated unique morphological findings. Ventricular walls and
trabeculations showed thick and random cellular structures. Atrioventricular and
semilunar valves were also thick but histological maturation was observed within a few weeks after cardiogenesis. The great arterial walls were thick and comprised of dense
cellular matrix. Morphologically, several characteristic findings, such as large atrial
appendages, the developmental process of formation of the membranous ventricular
septum and prominent coronary arteries, were recognised during this period. Heart
size increased linearly with gestation. Normal human fetal hearts demonstrate
geometrical development and histological and morphological maturation after the
period of cardiogenesis.
In comparison with human fetal hearts, mouse hearts demonstrate dramatic
morphological alterations during a short maturation period. Fetal mouse hearts show
some similar morphological findings to the human fetal heart, such as large atrial
appendages, lack of formation of the membranous septum, and thickened great
arterial walls. This suggests a shared mechanism of fetal heart maturation in mammals.
Detailed clinical information regarding cardiac morphology is vital for accurate
prenatal heart diagnosis in the first trimester. Fetal echocardiography in early
gestation has become routine practice. However, the technical limitations of image
acquisition and picture resolution make it difficult to visualize clear 3D images for fetal
cardiac diagnosis. Current modalities for clinical investigation by 3D echocardiography
do not have sufficient resolution to enable detailed morphological investigation of the
human fetal heart between 10th to 12th weeks of postmenstrual gestation. Only the
original data of the four-chamber view demonstrated no offsetting of the
atrioventricular valves as seen on HREM. Further technical advances in 3D echocardiography will be required to enable precise cardiac diagnosis in the first
trimester.
This thesis describes morphological development in normal human fetal hearts
for the first few weeks after cardiogenesis and contributes to a better understanding
of the normal appearances in the first trimester which is vital for future investigation
into the origin of congenital heart disease
