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

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 three-dimensional (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

High sensitivity X-ray phase contrast imaging by laboratory grating-based interferometry at high Talbot order geometry

X-ray phase contrast imaging is a powerful analysis technique for materials science and biomedicine. Here, we report on laboratory grating-based X-ray interferometry employing a microfocus X-ray source and a high Talbot order (35th) asymmetric geometry to achieve high angular sensitivity and high spatial resolution X-ray phase contrast imaging in a compact system (total length <1 m). The detection of very small refractive angles (∼50 nrad) at an interferometer design energy of 19 keV was enabled by combining small period X-ray gratings (1.0, 1.5 and 3.0 µm) and a single-photon counting X-ray detector (75 µm pixel size). The performance of the X-ray interferometer was fully characterized in terms of angular sensitivity and spatial resolution. Finally, the potential of laboratory X-ray phase contrast for biomedical imaging is demonstrated by obtaining high resolution X-ray phase tomographies of a mouse embryo embedded in solid paraffin and a formalin-fixed full-thickness sample of human left ventricle in water with a spatial resolution of 21.5 µm

A tomographic microscopy-compatible Langendorff system for the dynamic structural characterization of the cardiac cycle

ntroduction: Cardiac architecture has been extensively investigated ex vivo using a broad spectrum of imaging techniques. Nevertheless, the heart is a dynamic system and the structural mechanisms governing the cardiac cycle can only be unveiled when investigating it as such. Methods: This work presents the customization of an isolated, perfused heart system compatible with synchrotron-based X-ray phase contrast imaging (X-PCI). Results: Thanks to the capabilities of the developed setup, it was possible to visualize a beating isolated, perfused rat heart for the very first time in 4D at an unprecedented 2.75 μm pixel size (10.6 μm spatial resolution), and 1 ms temporal resolution. Discussion: The customized setup allows high-spatial resolution studies of heart architecture along the cardiac cycle and has thus the potential to serve as a tool for the characterization of the structural dynamics of the heart, including the effects of drugs and other substances able to modify the cardiac cycle

Automatic Generation of a Computational Model for Monopolar Stimulation of Cochlear Implants

International audienceCochlear implants have the potential to significantly improve severe sensorineural hearing loss. However, the outcome of this technique is highly variable and depends on patient-specific factors. We previously proposed a method for patient-specific electrical simulation after CI, which can assist in surgical planning of the CI and determination of the electrical stimulation pattern. However, the virtual implant placement and mesh generation were carried out manually and the process was not easily applied automatically for further cochlear anatomies. Moreover, in order to optimize the implant designs, it is important to develop a way to stimulate the results of the implantation in a population of virtual patients. In this work we propose an automatic framework for patient-specific electrical simulation in CI surgery. To the best of our knowledge, this is the first method proposed for patient-specific generation of hearing models which combines high-resolution imaging techniques, clinical CT data and virtual electrode insertion. Furthermore, we show that it is possible to use the computational models of virtual patients to simulate the results of the electrical activation of the implant in the cochlea and surrounding bone. This is an important step because it allows us to advance towards a complete surgical planning and implant optimization procedure

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment

Objectives: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. Methods: This was a prospective observational case–control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age‐matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA‐affected heart specimen, using synchrotron radiation‐based X‐ray phase‐contrast microcomputed tomography and histology, respectively. Results: We included 30 fetuses with CoA and 60 gestational age‐matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left‐to‐right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0–2.7) vs 1.8 (1.7–2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1–84.9) vs 47.0 (43.0–55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. Conclusions: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume‐loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life

Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging

Nowadays, unexplained cardiovascular diseases (CVD) and heart transplant response are assessed by qualitative histological analysis of extracted endomyocardial biopsies (EMB), which is a time consuming procedure involving structural damage of the tissue and the analysis in only a few slices of a 3D structure. In this paper we propose synchrotron radiation-based X-ray phase contrast imaging (X-PCI) as a suitable technique for the analysis of different cardiac microstructures, such as collagen matrix, cardiomyocytes and microvasculature, and how they are affected in abnormal conditions. Following an established procedure in clinics, biopsies from Wistar Kyoto rats are extracted, imaged with X-PCI, and processed in order to show that the quantification of the endomysial collagen matrix, cardiomyocytes and microvasculature is possible, thus demonstrating that the intrinsic properties of X-PCI make it a powerful technique for cardiac microstructure imaging and a promising methodology for a faster and more accurate EMB analysis for CVD diagnosis and evaluation

Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging

Nowadays, unexplained cardiovascular diseases (CVD) and heart transplant response are assessed by qualitative histological analysis of extracted endomyocardial biopsies (EMB), which is a time consuming procedure involving structural damage of the tissue and the analysis in only a few slices of a 3D structure. In this paper we propose synchrotron radiation-based X-ray phase contrast imaging (X-PCI) as a suitable technique for the analysis of different cardiac microstructures, such as collagen matrix, cardiomyocytes and microvasculature, and how they are affected in abnormal conditions. Following an established procedure in clinics, biopsies from Wistar Kyoto rats are extracted, imaged with X-PCI, and processed in order to show that the quantification of the endomysial collagen matrix, cardiomyocytes and microvasculature is possible, thus demonstrating that the intrinsic properties of X-PCI make it a powerful technique for cardiac microstructure imaging and a promising methodology for a faster and more accurate EMB analysis for CVD diagnosis and evaluation