Bruno Paun

Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography

Background While individual cardiac myocytes only have a limited ability to shorten, the heart efficiently pumps a large volume-fraction thanks to a cell organization in a complex 3D fibre structure. Subclinical subtle cardiac structural remodelling is often present before symptoms arise. Understanding and early detection of these subtle changes is crucial for diagnosis and prevention. Additionally, personalized computational modelling requires knowledge on the multi-scale structure of the whole heart and vessels. Methods and Results We developed a rapid acquisition together with visualization and quantification methods of the integrated microstructure of whole in-vitro rodents hearts using synchrotron based X-ray phase-contrast tomography. These images are formed not only by X-ray absorption by the tissue but also by wave propagation phenomena, enhancing structural information, thus allowing to raise tissue contrast to an unprecedented level. We used a (ex-vivo) normal rat heart and fetal rabbit hearts suffering intrauterine growth restriction as a model of subclinical cardiac remodelling to illustrate the strengths and potential of the technique. For comparison, histology and diffusion tensor magnetic resonance imaging was performed. Conclusions We have developed a novel, high resolution, image acquisition, and quantification approach to study a whole in-vitro heart at myofibre resolution, providing integrated 3D structural information at microscopic level without any need of tissue slicing and processing. This superior imaging approach opens up new possibilities for a systems approach towards analysing cardiac structure and function, providing rapid acquisition of quantitative microstructure of the heart in a near native state.

Patient independent representation of the detailed cardiac ventricular anatomy

&NA; Reparameterization of surfaces is a widely used tool in computer graphics known mostly from the remeshing algorithms. Recently, the surface reparameterization techniques started to gain popularity in the field of medical imaging, but mostly for convenient 2D visualization of the information initially represented on 3D surfaces (e.g. continuous bulls‐eye plot). However, by consistently mapping the 3D information to the same 2D domain, surface reparameterization techniques allow us to put into correspondence anatomical shapes of inherently different geometry. In this paper, we propose a method for anatomical parameterization of cardiac ventricular anatomies that include myocardium, trabeculations, tendons and papillary muscles. The proposed method utilizes a quasi‐conformal flattening of the myocardial surfaces of the left and right cardiac ventricles and extending it to cover the interior of the cavities using the local coordinates given by the solution of the Laplaces equation. Subsequently, we define a geometry independent representation for the detailed cardiac left and right ventricular anatomies that can be used for convenient visualization and statistical analysis of the trabeculations in a population. Lastly we show how it can be used for mapping the detailed cardiac anatomy between different hearts, which is of considerable interest for detailed cardiac computational models or shape atlases. HighlightsPatient independent anatomical parametrization of the detailed cardiac ventricular anatomy.Mapping between different cardiac geometries.Parametrization suitable for statistical analysis of the detailed ventricular anatomy.Framework for incorporating detailed anatomy into computational models. Graphical abstract Figure. No caption available.

Assessment of Myofiber Orientation in High Resolution Phase-Contrast CT Images

Complex helical organization of cardiac fibers is one of the key factors for efficient beat-to-beat contraction and electrical impulse propagation. Complete understanding of this (inter-individual) configuration is limited by image acquisition and analysis constraints. Consequently, extensive quantification of myofiber orientation and remodeling within diverse cases is still lacking. With its high resolution and contrast, synchrotron-based phase-contrast X-ray imaging offers potential for assessing this information. Although it recently gained increased attention for biomedical purposes, only few cardiac applications were presented to this date. In this paper, we used synchrotron-based acquisitions of a healthy fetal rabbit heart and implemented a structure tensor method for estimating fiber orientation. For comparison, we generated the common rule-based model, simulating fiber angles distribution for the given geometry. Although we find similar fiber angle transmural courses compared to the theoretical, high-resolution imaging and analysis show that the myocardium in an individual is more complex than often assumed.

Quantification of the detailed cardiac left ventricular trabecular morphogenesis in the mouse embryo

HighlightsFramework for regional cardiac ventricular myocardial complexity analysis in 3D.Longitudinal analysis and visualization of the myocardial complexity in a mouse embryo.Analysis performed using 3D fractal analysis and new physiologically meaningful complexity measures such as surface, volume and surface to volume ratios. Graphical abstract Figure. No caption available. ABSTRACT During embryogenesis, a mammalian heart develops from a simple tubular shape into a complex 4‐chamber organ, going through four distinct phases: early primitive tubular heart, emergence of trabeculations, trabecular remodeling and development of the compact myocardium. In this paper we propose a framework for standardized and subject‐independent 3D regional myocardial complexity analysis, applied to analysis of the development of the mouse left ventricle. We propose a standardized subdivision of the myocardium into 3D overlapping regions (in our case 361) and a novel visualization of myocardial complexity, whereupon we: 1) extend the fractal dimension, commonly applied to image slices, to 3D and 2) use volume occupied by the trabeculations in each region together with their surface area, in order to quantify myocardial complexity. The latter provides an intuitive characterization of the complexity, given that compact myocardium will tend to occupy a larger volume with little surface area while high surface area with low volume will correspond to highly trabeculated areas. Using 50 mouse embryo images at 5 different gestational ages (10 subjects per gestational age), we demonstrate how the proposed representation and complexity measures describe the development of LV myocardial complexity. The mouse embryo data was acquired using high resolution episcopic microscopy. The complexity analysis per region was carried out using: 3D fractal dimension, myocardial volume, myocardial surface area and ratio between the two. The analysis of gestational ages was performed on embryos of 14.5, 15.5, 16.5, 17.5 and 18.5 embryonic days, and demonstrated that the regional complexity of the trabeculations increases longitudinally from the base to the apex, with a maximum around the middle. The overall complexity decreases with gestational age, being most complex at 14.5. Circumferentially, at ages 14.5, 15.5 and 16.5, the trabeculations show similar complexity everywhere except for the anteroseptal and inferolateral area of the wall, where it is smaller. At 17.5 days, the regions of high complexity become more localized towards the inferoseptal and anterolateral parts of the wall. At 18.5 days, the high complexity area exhibits further localization at the inferoseptal and anterior part of the wall.

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high-resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high-performance computing. The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.

Left Ventricular Trabeculations Decrease the Wall Shear Stress and Increase the Intra-Ventricular Pressure Drop in CFD Simulations

The aim of the present study is to characterize the hemodynamics of left ventricular (LV) geometries to examine the impact of trabeculae and papillary muscles (PMs) on blood flow using high performance computing (HPC). Five pairs of detailed and smoothed LV endocardium models were reconstructed from high-resolution magnetic resonance images (MRI) of ex-vivo human hearts. The detailed model of one LV pair is characterized only by the PMs and few big trabeculae, to represent state of art level of endocardial detail. The other four detailed models obtained include instead endocardial structures measuring ≥1 mm2 in cross-sectional area. The geometrical characterizations were done using computational fluid dynamics (CFD) simulations with rigid walls and both constant and transient flow inputs on the detailed and smoothed models for comparison. These simulations do not represent a clinical or physiological scenario, but a characterization of the interaction of endocardial structures with blood flow. Steady flow simulations were employed to quantify the pressure drop between the inlet and the outlet of the LVs and the wall shear stress (WSS). Coherent structures were analyzed using the Q-criterion for both constant and transient flow inputs. Our results show that trabeculae and PMs increase the intra-ventricular pressure drop, reduce the WSS and disrupt the dominant single vortex, usually present in the smoothed-endocardium models, generating secondary small vortices. Given that obtaining high resolution anatomical detail is challenging in-vivo, we propose that the effect of trabeculations can be incorporated into smoothed ventricular geometries by adding a porous layer along the LV endocardial wall. Results show that a porous layer of a thickness of 1.2·10−2 m with a porosity of 20 kg/m2 on the smoothed-endocardium ventricle models approximates the pressure drops, vorticities and WSS observed in the detailed models.