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[Background] Non-invasive estimation of the pressure gradient in aortic coarctation has much clinical importance in assisting the diagnosis and treatment of the disease. Previous researchers applied computational fluid dynamics for the prediction of the pressure gradient in aortic coarctation. The accuracy of the prediction was satisfactory but the procedure was time-consuming and resource-demanding., [Method] In this research a magnetic resonance imaging (MRI)-based non-invasive modeling procedure is implemented to predict the pressure gradient in 14 patient cases of aortic coarctation. Multi-cycle patient flow and pressure data are processed to produce the flow and pressure conditions in the patient cases. Bernoulli equation-based friction loss model combined with the inertial effect of the blood flow in the vessel segments are applied to model the pressure gradient in the aortic coarctation. The model-predicted pressure gradient data are then compared with the catheter in vivo measurement data for validation., [Results] The MRI-based model prediction technique produces results that are consistent with those from the catheter measurement, based on the criteria of both the cycle-averaged instantaneous pressure gradient and the peak-to-peak pressure gradient., [Conclusion] This study suggests that the MRI-based non-invasive modeling procedure has much potential to be applied in clinical practice for the prediction of the pressure gradient in aortic coarctation patients., This research was supported by the European Commission's Seventh Framework Programme (FP7/2007-2013) under the grant agreement number 224495 (euHeart project).

Objectives The aim of this study was to develop a computer model that accurately predicts myocardial fractional flow reserve (FFR) from angiographic images alone, in patients with coronary artery disease. Background Percutaneous coronary intervention (PCI) guided by FFR is superior to standard assessment alone. FFR-guided PCI results in improved clinical outcomes, a reduction in the number of stents implanted, and reduced cost. Currently FFR is used in few patients. A less invasive FFR would be a valuable tool. Methods Nineteen patients with stable coronary artery disease awaiting elective PCI were studied. They underwent rotational coronary angiography. The FFR was measured, physiologically significant lesions were stented, and angiography and FFR were repeated. Three-dimensional arterial anatomy pre- and post-stenting was reconstructed offline. Generic boundary conditions for computational fluid dynamics analysis were applied. The virtual fractional flow reserve (vFFR) and measured fractional flow reserve (mFFR) values were compared. Results Thirty-five matched anatomical and physiological datasets were obtained: 10 right coronary arteries (RCA) (5 pre- and post-stenting), and 12 left coronary arteries (LCA) (8 pre- and post-stenting). The computational fluid dynamics model predicted which lesions were physiologically significant (FFR 0.80) with accuracy, sensitivity, specificity, positive and negative predictive values of 97%, 86%, 100%, 100%, and 97% respectively. On average, the vFFR values deviated from mFFR by ±0.06 (mean delta = 0.02, SD = 0.08). The vFFR and mFFR were closely correlated (r = 0.84). Conclusions We have developed a model of intracoronary physiology based upon a rotational coronary angiogram. Significant lesions were identified with 97% accuracy. The FFR was reliably predicted without the need for invasive measurements or inducing hyperemia.

This paper presents an application of Bond Graphs in physiological modelling. In this work, a Bond Graph model is utilised as boundary condition for a detailed model of an idealized mitral valve. Applications of this type fit within the framework described by the “Virtual Physiological Human” initiative. This supports the integration of physical, mechanical and biochemical models encompassing a range of different length and time scales to obtain predictive models of the human body. Because 3D detailed modelling and simulation is computationally intensive, a 3D computational model of a whole biological system is, by today’s standards, impossible to achieve. Due to their unique multi-physics nature of internal coherence, Bond Graphs are particularly suited to biological applications and can be coupled to 3D models and lumped parameter models. A specific application in cardiovascular modelling is demonstrated by focusing on a specific example; a 3D model of the mitral valve coupled to a lumped parameter model of the left ventricle.

In this paper we describe an extension of the lattice Boltzmann method to simulate blood clotting based on a simple residence time model. Simulation results of a stenosed model artery are presented together with experimental blood analogue results. Aspects of an efficient unstructured implementation are briefly reviewed.

In this paper, the concurrent numerical simulation of clotting and unsteady flow within a stenosed artery is described. The simplified blood clotting process is based on a residence time model, using a lattice Boltzmann flow solver with passive scalar advective-diffusive transport. Simulation results of a stenosed model artery are presented together with experimental blood analogue results. Aspects of an efficient unstructured implementation are briefly reviewed.

There is evidence that glutaraldehyde used routinely in the fixation process of bioprosthetic heart valves may be a major factor in their subsequent calcification. A further complication is introduced by the use of a formaldehyde treatment step, whether for sterilization or storage. The effects of this second aldehyde on calcification is also unknown. The aim of the present work is to determine the degree of glutaraldehyde and formaldehyde incorporation into commercial valve leaflets and to establish whether there is a relationship between the aldehyde treatment and tissue calcification. Both pre- and post-implantation concentrations of aldehydes were estimated by high performance liquid chromatography of acid hydrolyzates of commercial valve tissue. Control samples were taken from freshly prepared porcine aortic valves and bovine pericardium fixed in glutaraldehyde. The degree of calcification was investigated using the rat subcutaneous implant model. Samples were retrieved after 56 days and calcium estimated by atomic absorption spectroscopy. The results indicated that storage of both porcine and pericardial valves for periods of 5 years or longer reduced calcification. A greater reduction in calcification was noted when tissue was treated sequentially with glutaraldehyde and formaldehyde rather than glutaraldehyde alone. From this work it can be concluded that bioprosthetic valves calcify less in the rat model when they are stored for extended periods of time in glutaraldehyde solution. This effect is enhanced when formaldehyde storage is employed.

When simulating the systole i.e the closure of the valve and the regurgitant flow, the maximum velocity along a target line located in the atrium chamber at 6 mm away from the hinges was monitored. As the 3 panel in fig. 1 shows, the first velocity peak of ~2 m/s occurred during the valve closure. The second velocity peak occurred during the early systole, immediately after the complete closure of the valve. The third velocity peak was found later, after the peak systole.

Within minutes following stent implantation, a series of pathophysiologic responses are incited in the vasculature, namely thrombosis and inflammation, leading to the onset of a neointimal hyperplasia (NIH) growth termed in-stent restenosis (ISR) [Edelman, 1998]. The thrombus formation initiates through platelet aggregation onto the partially denuded arterial wall and exposed stent struts. It has been suggested that the degree to which platelets adhere to the stent surface is dependent on the direction of the local flow field with respect to wall position [Duraiswamy, 2005], in addition to activation by low flow or stagnant velocity patterns [Kroll, 1996]. This study aims to elucidate the correlation between the local flow field hypotheses and in vivo NIH response of the coronary artery to stenting through utilization of micro-CT reconstruction of the deformed stent geometry following implantation.

Aortic coarctation is a narrowing of part of the aorta due to the congenital defect. It causes abnormally elevated after-load to the left heart and thus impaired blood supply to the peripheral organs. Currently diagnosis and treatment of aortic coarctation are still difficult issues due to the complex haemodynamic changes involved [Keshavarz-Motamed, 2011]. The EU FP7 euHeart project is developing numerical tools to assist clinicians in the diagnostic evaluation of aortic coarctation based on MRI images of patients. The pressure gradient across the aorta in a patient-specific anatomy is computed by 3D computational fluid dynamics, but the result is critically dependent on the balance of the measured ascending aortic flow that is distributed to the supra-aortic vessels and the descending aorta. The balance is achieved using Windkessel models at the four outlets. The process of tuning the Windkessels in combination with the 3D model to match the (noisy) clinical flow measurements is computationally expensive and is sensitive to the initialisation. We propose the use of an intermediate 1D/0D model, based on the geometry of the patient aorta, to pre-tune the system.

Obstructive coronary artery disease is a manifestation of ischemic heart disease, the most common cause of death in the world. At present, stents are used in more than 70% of percutaneous coronary interventions. A disadvantage of the technique is represented by in-stent restenosis, a common and difficult to treat re-narrowing of the artery [Gunn, 2002], which often occurs a few months after this intervention and may be linked to the local stress caused by the stent struts [Arjomand, 2003]. Evaluating the distribution and magnitude of stress within the vessel after stenting is important to study the stimuli for tissue growth. Stent-vessel interaction has been analyzed in literature, often using stent models with perfectly symmetric expansion. Uneven stent strut distribution has been observed in histological images from experimental animal models [Gunn, 2002]. This study considers the influence of uneven stent strut distribution in a coronary artery model.

Atherosclerotic lesions are widely reported to be associated with areas of low and oscillating wall shear stress [Asakura 2006]. The mechanisms underlying this relationship are poorly understood. We propose that a filamentous, high molecularweight form of the haemostatic protein von Willebrand Factor (ultra-large von Willebrand Factor; ULVWF) is involved in this process. VWF promotes an inflammatory response by the recruitment of platelets and leukocytes to these areas of the vasculature.

Computer simulations and rule-based modelling can be effective methodologies to describe complex systems and understand or control their behaviour. As many complex biological systems encompass several spatial and temporal scales, as well as several elementary components they cannot be described by a single homogenous model. COAST is developing a multi-scale, multi-science framework coined ‘Complex Automata’ for modelling and simulation of complex systems. The key tenet of COAST is that a multi-scale system can be decomposed into a number of single-scale Cellular Automata or agent-based models that mutually interact across the scales. Decomposition is facilitated by building a Scale Separation Map (SSM) on which each single-scale system is represented according to its spatial and temporal characteristics. Processes having well-separated scales are thus easily identified as the fundamental components of the multi-scale model.

Eighteen explanted pericardial heterografts were studied (16 standard Ionescu-Shiley, one Hancock, and one Mitroflow). Regurgitation was the reason given for explantation of all the Ionescu-Shiley valves. The other two valves were removed for technical reasons. All the Ionescu-Shiley valves had commissural tears and there was concomitant gross calcification in 10 of the 16 valves. In addition, an apparent increase in cusp area had caused “leaflet sagging.” The explanted leaflets were thicker and stiffer than leaflets from an unimplanted valve. These features were confirmed directly with an animal model of subcutaneous implantation. Examination with an electron microscope revealed that these changes in mechanical properties seemed to be linked to fiber separation and infiltration by an amorphous proteinlike matrix. The durability of the glutaraldehyde-fixed pericardium depended on a number of factors. Early and midterm failure appeared to be stress induced. Predisposition to high mechanical stresses near the stent was exacerbated by the changes induced by the host environment. This problem was aggravated further in the Ionescu-Shiley valves by stress concentrations around the hole associated with the holding suture. In the long term, collagen disruption associated with leaflet flexure was followed by secondary calcification at the boundary between the intact and disrupted material.

The mechanical properties of five different, equally distributed, and randomly oriented sites in natural and glutaraldehyde-fixed calf pericardial sacs were investigated. Identical sites in different sacs were obtained by placing a template over each sac and using the ligaments still attached to the pericardium as a reference frame. Mean maximum extension of the fixed tissue was statistically significantly greater than that of natural tissue at the same degree of stress. There was no significant difference in thickness from position to position within a sac, from sac to sac, or from the natural to fixed pericardium. However, the extensibility of one particular site was significantly greater than that of other positions in the pericardial sac. This position lay entirely in a well-defined sector that emanated radially from the pericardial ligaments. Light and electron microscopy showed no difference in collagen structure in the five positions studied. In contrast, both the content and ultrastructure of the tissue elastin differed in the region of high extensibility compared with those sites studied in the remainder of the sac. This region contained coarse condensed elastin whereas the other sites had fine elastin dispersed diffusely throughout the tissue. These results suggest that pericardial heterografts of uniform thickness may be harvested from any position in calf pericardium. However, unless the region of coarse condensed elastin is excluded, leaflets with significantly different mechanical properties may be produced.