Cardiac multi-scale investigation of the right and left ventricle ex vivo: a review

Abstract

The heart is a complex multi-scale system composed of components integrated at the subcellular, cellular, tissue and organ levels. The myocytes, the contractile elements of the heart, form a complex threedimensional (3D) network which enables propagation of the electrical signal that triggers the contraction to efficiently pump blood towards the whole body. Cardiovascular diseases (CVDs), a major cause of mortality in developed countries, often lead to cardiovascular remodeling affecting cardiac structure and function at all scales, from myocytes and their surrounding collagen matrix to the 3D organization of the whole heart. As yet, there is no consensus as to how the myocytes are arranged and packed within their connective tissue matrix, nor how best to image them at multiple scales. Cardiovascular imaging is routinely used to investigate cardiac structure and function as well as for the evaluation of cardiac remodeling in CVDs. For a complete understanding of the relationship between structural remodeling and cardiac dysfunction in CVDs, multi-scale imaging approaches are necessary to achieve a detailed description of ventricular architecture along with cardiac function. In this context, ventricular architecture has been extensively studied using a wide variety of imaging techniques: ultrasound (US), optical coherence tomography (OCT), microscopy (confocal, episcopic, light sheet, polarized light), magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and, more recently, synchrotron X-ray phase contrast imaging (SR X-PCI). Each of these techniques have their own set of strengths and weaknesses, relating to sample size, preparation, resolution, 2D/3D capabilities, use of contrast agents and possibility of performing together with in vivo studies. Therefore, the combination of different imaging techniques to investigate the same sample, thus taking advantage of the strengths of each method, could help us to extract the maximum information about ventricular architecture and function. In this review, we provide an overview of available and emerging cardiovascular imaging techniques for assessing myocardial architecture ex vivo and discuss their utility in being able to quantify cardiac remodeling, in CVDs, from myocyte to whole organ.

A Review of Ex Vivo X-ray Microfocus Computed Tomography-Based Characterization of the Cardiovascular System

“…The proper functioning of the heart depends, among other things, on the complex organization of its myofibers. Since the action potential propagation is prescribed by the microstructure and the precise orientation of the cardiomyocytes, the myocardium has often been investigated using a broad variety of techniques [ 84 ]. Both CE-CT and PC-CT have been widely applied to image the ventricle microstructure, since the anisotropic 3D orientation of the fibers can be scarcely extracted by the histological analysis [ 85 ].…”

Osteopathic Palpation of the Heart

“…The orientation of the myocytes not only determines the contraction but also the electrical expression of the heart [ 14 ]. The longitudinal orientation of the myocytes, with respect to the long axis of the ventricular cavity, is called the helical angle; the myocyte radial orientation with respect to the epicardial surface is known as the intrusion angle [ 22 ]. The angle formed by the myocyte mass and the epicardial surface is called the E3 angle [ 22 ].…”

“…The longitudinal orientation of the myocytes, with respect to the long axis of the ventricular cavity, is called the helical angle; the myocyte radial orientation with respect to the epicardial surface is known as the intrusion angle [ 22 ]. The angle formed by the myocyte mass and the epicardial surface is called the E3 angle [ 22 ]. Sub-epicardial fibers form a counterclockwise or left-handed helix while sub-endocardial fibers form a clockwise or right-handed helix.…”

“…Sub-epicardial fibers form a counterclockwise or left-handed helix while sub-endocardial fibers form a clockwise or right-handed helix. The left ventricle has greater compactness than the right one, which is more complex and with greater trabeculae [ 22 ]. In an overall view, we could see the heart as a skein of threads while it is no longer possible to imagine the heart as a mere pump.…”

A groupwise registration and tractography framework for cardiac myofiber architecture description by diffusion MRI: an application to the ventricular junctions

“…It therefore offers a better image quality compared to clinical acquisition providing an excellent research tool for anatomical investigation or validation of in vivo techniques. Among all the ex-vivo studies using DTI, there is a large amount of evidence depicting the typical organization of the left ventricle (LV) myocardium characterized by the helix angle variation through the transmural wall [28][29][30][31]. Only a few studied describe sheetlets arrangement and fiber organization in both the LV and RV [30,31].…”