Detailed quantification of cardiac ventricular myocardial architecture in the embryonic and fetal mouse heart by application of structure tensor analysis to high resolution episcopic microscopic data

Abstract

The mammalian heart, which is one of the first organs to form and function during embryogenesis, develops from a simple tube into a complex organ able to efficiently pump blood towards the rest of the body. The progressive growth of the compact myocardium during embryonic development is accompanied by changes in its structural complexity and organisation. However, how myocardial myoarchitecture develops during embryogenesis remain poorly understood. To date, analysis of heart development has focused mainly on qualitative descriptions using selected 2D histological sections. High resolution episcopic microscopy (HREM) is a novel microscopic imaging technique that enables to obtain high-resolution three-dimensional images of the heart and perform detailed quantitative analyses of heart development. In this work, we performed a detailed characterization of the development of myocardial architecture in wildtype mice, from E14.5 to E18.5, by means of structure tensor analysis applied to HREM images of the heart. Our results shows that even at E14.5, myocytes are already aligned, showing a gradual change in their helical angle from positive angulation in the endocardium towards negative angulation in the epicardium. Moreover, there is gradual increase in the degree of myocardial organisation concomitant with myocardial growth. However, the development of the myoarchitecture is heterogeneous showing regional differences between ventricles, ventricular walls as well as between myocardial layers, with different growth patterning between the endocardium and epicardium. We also found that the percentage of circumferentially arranged myocytes within the LV significantly increases with gestational age. Finally, we found that fractional anisotropy (FA) within the LV gradually increases with gestational age, while the FA within RV remains unchanged.

Quantitative Image Processing for Three-Dimensional Episcopic Images of Biological Structures: Current State and Future Directions

“…Other quantification methods began appearing in papers from 2017 onwards. Analysis of cell orientation was performed in three papers [ 2 , 22 , 23 ]. Carcia-Canadilla et al [ 23 ] calculated the orientation of cardiomyocytes from HREM images using a structure tensor method developed in-house, and quantified the uniformity of myocyte orientation to demonstrate that disorganization of cardiomyocytes can be seen before birth in mouse models of hypertrophic cardiomyopathy.…”

Quantitative Image Processing for Three-Dimensional Episcopic Images of Biological Structures: Current State and Future Direction

“…Other quantification methods began appearing in papers from 2017 onwards. These include structure tensor analysis for calculating myocyte and neuron orientation [6,19,20], skeletonization algorithms for producing a graphical representation of vasculature [6,21], and measures of asymmetry [22].…”

Quantitative Image Processing for Three-Dimensional Episcopic Images of Biological Structures: Current State and Future Directions

“…Other quantification methods began appearing in papers from 2017 onwards. Analysis of cell orientation was performed in three papers [2,23,24]. Carcia-Canadilla et.…”

“…Standardized analysis allows these results to be easily interpreted and compared with results published elsewhere.Other quantification methods began appearing in papers from 2017 onwards. Analysis of cell orientation was performed in three papers[2,23,24]. Carcia-Canadilla et.…”