Abstract

ObjectiveHuman myocardium has a complex and anisotropic 3D fiber pattern. It remains unknown, however, when in fetal life this anisotropic pattern develops and whether the human heart is structurally fully mature at birth. We aimed here to use diffusion tensor MRI (DTI) tractography to characterize the evolution of fiber architecture in the developing human fetal heart.MethodsHuman fetal hearts (n = 5) between 10–19 weeks of gestation were studied. The heart from a 6-day old neonate and an adult human heart served as controls. The degree of myocardial anisotropy was measured by calculating the fractional anisotropy (FA) index. In addition, fiber tracts were created by numerically integrating the primary eigenvector field in the heart into coherent streamlines.ResultsAt 10–14 weeks the fetal hearts were highly isotropic and few tracts could be resolved. Between 14–19 weeks the anisotropy seen in the adult heart began to develop. Coherent fiber tracts were well resolved by 19 weeks. The 19-week myocardium, however, remained weakly anisotropic with a low FA and no discernable sheet structure.ConclusionsThe human fetal heart remains highly isotropic until 14–19 weeks, at which time cardiomyocytes self-align into coherent tracts. This process lags 2–3 months behind the onset of cardiac contraction, which may be a prerequisite for cardiomyocyte maturation and alignment. No evidence of a connective tissue scaffold guiding this process could be identified by DTI. Maturation of the heart’s sheet structure occurs late in gestation and evolves further after birth.

Highlights

  • The myocardium is an anisotropic tissue in which the constituent cardiomyocytes (CMs) are arranged in a complex 3D network [1]

  • The aim of the current study was, to use diffusion tensor magnetic resonance imaging (DTI) tractography to characterize the development of myofiber architecture in the human fetal heart

  • The ellipsoidal glyphs form a coherent and ordered pattern throughout the left ventricle (LV) and have a prolate shape representing a high degree of structural anisotropy

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Summary

Introduction

The myocardium is an anisotropic tissue in which the constituent cardiomyocytes (CMs) are arranged in a complex 3D network [1]. Fibers in the subendocardium have a positive helix angle (HA) and those in the subepicardium a negative HA, while fibers in the midmyocardium are circumferential [1,7] It remains unknown, when in fetal life and by what mechanisms this architectural pattern develops. The aim of the current study was, to use diffusion tensor magnetic resonance imaging (DTI) tractography to characterize the development of myofiber architecture in the human fetal heart. We hypothesize that this knowledge has the potential to elucidate the pathogenesis of a broad range of congenital heart defects and to provide a valuable template for the regeneration of functional myocardium in the adult

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