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Title: Investigation into the 3D structure of the developing human fetal heart
Author: Matsui, Hikoro
ISNI:       0000 0004 2715 0471
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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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.
Supervisor: Gardiner, Helena ; Kumar, Sailesh ; Ho, Yen Sponsor: Tiny Tickers ; Richard and Jack Wiseman Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral