A computational human mitral valve (MV) model under physiological pressure loading is developed using a hybrid finite element immersed boundary method, which incorporates experimentally-based constitutive laws in a three-dimensional fluid-structure interaction framework. A transversely isotropic material constitutive model is used to characterize the mechanical behaviour of the MV tissue based on recent mechanical tests of healthy human mitral leaflets. Our results show good agreement, in terms of the flow rate and the closing and opening configurations, with measurements from in vivo magnetic resonance images. The stresses in the anterior leaflet are found to be higher than those in the posterior leaflet and are concentrated around the annulus trigons and the belly of the leaflet. The results also show that the chordae play an important role in providing a secondary orifice for the flow when the valve opens. Although there are some discrepancies to be overcome in future work, our simulations show that the developed computational model is promising in mimicking the in vivo MV dynamics and providing important information that are not obtainable by in vivo measurements. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Understanding the interaction between the valves and walls of the heart is important in assessing and subsequently treating heart dysfunction. This study presents an integrated model of the mitral valve (MV) coupled to the left ventricle (LV), with the geometry derived from in vivo clinical magnetic resonance images. Numerical simulations using this coupled MV-LV model are developed using an immersed boundary/finite element method. The model incorporates detailed valvular features, left ventricular contraction, nonlinear soft tissue mechanics, and fluid-mediated interactions between the MV and LV wall. We use the model to simulate cardiac function from diastole to systole. Numerically predicted LV pump function agrees well with in vivo data of the imaged healthy volunteer, including the peak aortic flow rate, the systolic ejection duration, and the LV ejection fraction. In vivo MV dynamics are qualitatively captured. We further demonstrate that the diastolic filling pressure increases significantly with impaired myocardial active relaxation to maintain a normal cardiac output. This is consistent with clinical observations. The coupled model has the potential to advance our fundamental knowledge of mechanisms underlying MV-LV interaction, and help in risk stratification and optimisation of therapies for heart diseases.

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state‐of‐the‐art modelling of the mitral valve, including static and dynamics models, models with fluid‐structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed.

We develop a fluid–structure interaction (FSI) model of the mitral valve (MV) that uses an anatomically and physiologically realistic description of the MV leaflets and chordae tendineae. Three different chordae models—complex, ‘pseudo-fibre’ and simplified chordae—are compared to determine how different chordae representations affect the dynamics of the MV. The leaflets and chordae are modelled as fibre-reinforced hyperelastic materials, and FSI is modelled using an immersed boundary–finite element method. The MV model is first verified under static boundary conditions against the commercial finite element software ABAQUS and then used to simulate MV dynamics under physiological pressure conditions. Interesting flow patterns and vortex formulation are observed in all three cases. To quantify the highly complex system behaviour resulting from FSI, an energy budget analysis of the coupled MV FSI model is performed. Results show that the complex and pseudo-fibre chordae models yield good valve closure during systole but that the simplified chordae model leads to poorer leaflet coaptation and an unrealistic bulge in the anterior leaflet belly. An energy budget analysis shows that the MV models with complex and pseudo-fibre chordae have similar energy distribution patterns but the MV model with the simplified chordae consumes more energy, especially during valve closing and opening. We find that the complex chordae and pseudo-fibre chordae have similar impact on the overall MV function but that the simplified chordae representation is less accurate. Because a pseudo-fibre chordal structure is easier to construct and less computationally intensive, it may be a good candidate for modelling MV dynamics or interaction between the MV and heart in patient-specific applications.

No abstract

Background Tumor microenvironment (TME) including the immune checkpoint system impacts prognosis in some types of malignancy. The aim of our study was to investigate the precise prognostic significance of the TME profile in endometrial carcinoma. Methods We performed immunohistochemistry of the TME proteins, PD-L1, PD-1, CD4, CD8, CD68, and VEGF in endometrial carcinomas from 221 patients. Results High PD-L1 in tumor cells (TCs) was associated with better OS (p = 0.004), whereas high PD-L1 in tumor-infiltrating immune cells (TICs) was associated with worse OS (p = 0.02). High PD-L1 in TICs correlated with high densities of CD8+ TICs and CD68+ TICs, as well as microsatellite instability (p = 0.00000064, 0.00078, and 0.0056), while high PD-L1 in TCs correlated with longer treatment-free interval (TFI) after primary chemotherapy in recurrent cases (p = 0.000043). High density of CD4+ TICs correlated with better OS and longer TFI (p = 0.0008 and 0.014). Univariate and multivariate analyses of prognostic factors revealed that high PD-L1 in TCs and high density of CD4+ TICs were significant and independent for favorable OS (p = 0.014 and 0.0025). Conclusion The current findings indicate that PD-L1 and CD4+ helper T cells may be reasonable targets for improving survival through manipulating chemosensitivity, providing significant implications for combining immunotherapies into the therapeutic strategy for endometrial carcinoma.

No abstract

The distribution of collagen fibres plays a significant role in the mechanical behaviour of artery walls. Experimental data show that in most artery wall layers there are two (or more) in-plane symmetrically disposed families of fibres. However, a recent investigation revealed that some artery wall layers have only one preferred fibre direction, notably in the medial layer of human common iliac arteries. This paper aims to provide a possible explanation for this intriguing phenomenon. An invariant-based constitutive model is utilized to characterize the mechanical behaviour of tissues. We then use three different hypotheses to determine the ‘optimal fibre angle’ in an iliac artery model. All three hypotheses lead to the same result that the optimal fibre angle in the medial layer of the iliac artery is close to the circumferential direction. The axial pre-stretch, in particular, is found to play an essential role in determining the optimal fibre angle.