FEniCS implementation of the Virtual Fields Method (VFM) for nonhomogeneous hyperelastic identification

It is of great significance to identify the nonhomogeneous distribution of material properties in human tissues for different clinical and medical applications. This leads to the requirement of solving an inverse problem in elasticity. The virtual fields method (VFM) is a rather recent inverse method with remarkable computational efficiency compared with the optimization-based methods. In this study, we aim to identify nonhomogeneous hyperelastic material properties using the VFM. We propose two novel algorithms, RE-VFM and NO-VFM. In RE-VFM, the solid is partitioned in different regions and the elastic properties of each region are determined. In NO-VFM, 2 the distribution of elastic properties is completely reconstructed through the inverse problem without partitioning the solid. As the VFM requires to use virtual fields, we proposed an efficient way to construct them and implemented the approach in the FEniCS package. We validated the proposed methods on several examples, including a bilayer structure, a lamina cribosa (LC) model and a cube model embedded with a spherical inclusion. The numerical examples illustrate the feasibility of both RE-VFM and NO-VFM. Notably, the spatial variations of the Young's modulus distribution can be recovered accurately within only 5 iterations. The obtained results reveal the potential of the proposed methods for future clinical applications such as estimating the risk of vision loss related to glaucoma and detecting tumors.Comment: Advances in Software Engineering, In pres

Computational modeling of multiple myeloma interactions with resident bone marrow cells

The interaction of multiple myeloma with bone marrow resident cells plays a key role in tumor progression and the development of drug resistance. The tumor cell response involves contact-mediated and paracrine interactions. The heterogeneity of myeloma cells and bone marrow cells makes it difficult to reproduce this environment in in-vitro experiments. The use of in-silico established tools can help to understand these complex problems. In this article, we present a computational model based on the finite element method to define the interactions of multiple myeloma cells with resident bone marrow cells. This model includes cell migration, which is controlled by stress–strain equilibrium, and cell processes such as proliferation, differentiation, and apoptosis. A series of computational experiments were performed to validate the proposed model. Cell proliferation by the growth factor IGF-1 is studied for different concentrations ranging from 0–10 ng/mL. Cell motility is studied for different concentrations of VEGF and fibronectin in the range of 0–100 ng/mL. Finally, cells were simulated under a combination of IGF-1 and VEGF stimuli whose concentrations are considered to be dependent on the cancer-associated fibroblasts in the extracellular matrix. Results show a good agreement with previous in-vitro results. Multiple myeloma growth and migration are shown to correlate linearly to the IGF-1 stimuli. These stimuli are coupled with the mechanical environment, which also improves cell growth. Moreover, cell migration depends on the fiber and VEGF concentration in the extracellular matrix. Finally, our computational model shows myeloma cells trigger mesenchymal stem cells to differentiate into cancer-associated fibroblasts, in a dose-dependent manner

Abnormal Tissue Zone Detection and Average Active Stress Estimation in Patients with LV Dysfunction

Detection of regional ventricular dysfunction is a challenging problem. This study presents an efficient method based on ultrasound (US) imaging and finite element (FE) analysis, for detecting akinetic and dyskinetic regions in the left ventricle (LV). The underlying hypothesis is that the contraction of a healthy LV is approximately homogeneous. Therefore, any deviations between the image-based measured deformation and a homogeneous contraction FE model should correspond to a pathological region. The method was first successfully applied to synthetic data simulating an acute ischemia; it demonstrated that the pathological areas were revealed with a higher contrast than those observed directly in the deformation maps. The technique was then applied to a cohort of eight left bundle branch block (LBBB) patients. For this group, the heterogeneities were significantly less pronounced than those revealed for the synthetic cases but the method was still able to identify the abnormal regions of the LV. This study indicated the potential clinical utility of the method by its simplicity in a patient-specific context and its ability to quickly identify various heterogeneities in LV function. Further studies are required to determine the model accuracy in other pathologies and to investigate its robustness to noise and image artifacts

Machine learning and reduced order modelling for the simulation of braided stent deployment

Endoluminal reconstruction using flow diverters represents a novel paradigm for the minimally invasive treatment of intracranial aneurysms. The configuration assumed by these very dense braided stents once deployed within the parent vessel is not easily predictable and medical volumetric images alone may be insufficient to plan the treatment satisfactorily. Therefore, here we propose a fast and accurate machine learning and reduced order modelling framework, based on finite element simulations, to assist practitioners in the planning and interventional stages. It consists of a first classification step to determine a priori whether a simulation will be successful (good conformity between stent and vessel) or not from a clinical perspective, followed by a regression step that provides an approximated solution of the deployed stent configuration. The latter is achieved using a non-intrusive reduced order modelling scheme that combines the proper orthogonal decomposition algorithm and Gaussian process regression. The workflow was validated on an idealised intracranial artery with a saccular aneurysm and the effect of six geometrical and surgical parameters on the outcome of stent deployment was studied. The two-step workflow allows the classification of deployment conditions with up to 95% accuracy and real-time prediction of the stent deployed configuration with an average prediction error never greater than the spatial resolution of 3D rotational angiography (0.15 mm). These results are promising as they demonstrate the ability of these techniques to achieve simulations within a few milliseconds while retaining the mechanical realism and predictability of the stent deployed configuration

Mechanics-driven mechanobiological mechanisms of arterial tortuosity

[EN] Arterial tortuosity manifests in many conditions, including hypertension, genetic mutations predisposing to thoracic aortopathy, and vascular aging. Despite evidence that tortuosity disrupts efficient blood flow and that it may be an important clinical biomarker, underlying mechanisms remain poorly understood but are widely appreciated to be largely biomechanical. Many previous studies suggested that tortuosity may arise via an elastic structural buckling instability, but the novel experimental-computational approach used here suggests that tortuosity arises from mechanosensitive, cell-mediated responses to local aberrations in the microstructural integrity of the arterial wall. In particular, computations informed by multimodality imaging show that aberrations in elastic fiber integrity, collagen alignment, and collagen turnover can lead to a progressive loss of structural stability that entrenches during the development of tortuosity. Interpreted in this way, microstructural defects or irregularities of the arterial wall initiate the condition and hypertension is a confounding factor.This work was supported by grants from the U.S. NIH (R01 HL105297, P01 HL134605, and U01 HL142518)Weiss, D.; Cavinato, C.; Gray, A.; Ramachandra, AB.; Avril, S.; Humphrey, JD.; Latorre, M. (2020). Mechanics-driven mechanobiological mechanisms of arterial tortuosity. Science Advances. 6(49):1-26. https://doi.org/10.1126/sciadv.abd357412664

Cell nucleus elastography with the adjoint-based inverse solver

Background and Objectives: The mechanics of the nucleus depends on cellular structures and architecture, and impact a number of diseases. Nuclear mechanics is yet rather complex due to heterogeneous distribution of dense heterochromatin and loose euchromatin domains, giving rise to spatially variable stiffness properties. Methods: In this study, we propose to use the adjoint-based inverse solver to identify for the first time the nonhomogeneous elastic property distribution of the nucleus. Inputs of the inverse solver are deformation fields measured with microscopic imaging in contracting cardiomyocytes. Results: The feasibility of the proposed method is first demonstrated using simulated data. Results indicate accurate identification of the assumed heterochromatin region, with a maximum relative error of less than 5%. We also investigate the influence of unknown Poisson's ratio on the reconstruction and find that variations of the Poisson's ratio in the range [0.3-0.5] result in uncertainties of less than 15% in the identified stiffness. Finally, we apply the inverse solver on actual deformation fields acquired within the nuclei of two cardiomyocytes. The obtained results are in good agreement with the density maps obtained from microscopy images. Conclusions: Overall, the proposed approach shows great potential for nuclear elastography, with promising value for emerging fields of mechanobiology and mechanogenetics

Fast strain mapping in abdominal aortic aneurysm wall reveals heterogeneous patterns

Abdominal aortic aneurysm patients are regularly monitored to assess aneurysm development and risk of rupture. A preventive surgical procedure is recommended when the maximum aortic antero-posterior diameter, periodically assessed on two-dimensional abdominal ultrasound scans, reaches 5.5 mm. Although the maximum diameter criterion has limited ability to predict aneurysm rupture, no clinically relevant tool that could complement the current guidelines has emerged so far. In vivo cyclic strains in the aneurysm wall are related to the wall response to blood pressure pulse, and therefore, they can be linked to wall mechanical properties, which in turn contribute to determining the risk of rupture. This work aimed to enable biomechanical estimations in the aneurysm wall by providing a fast and semi-automatic method to post-process dynamic clinical ultrasound sequences and by mapping the cross-sectional strains on the B-mode image. Specifically, the Sparse Demons algorithm was employed to track the wall motion throughout multiple cardiac cycles. Then, the cyclic strains were mapped by means of radial basis function interpolation and differentiation. We applied our method to two-dimensional sequences from eight patients. The automatic part of the analysis took under 1.5 min per cardiac cycle. The tracking method was validated against simulated ultrasound sequences, and a maximum root mean square error of 0.22 mm was found. The strain was calculated both with our method and with the established finite-element method, and a very good agreement was found, with mean differences of one order of magnitude smaller than the image spatial resolution. Most patients exhibited a strain pattern that suggests interaction with the spine. To conclude, our method is a promising tool for investigating abdominal aortic aneurysm wall biomechanics as it can provide a fast and accurate measurement of the cyclic wall strains from clinical ultrasound sequences

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Patient-Specific Numerical Simulations of Endovascular Procedures in Complex Aortic Pathologies: Review and Clinical Perspectives

International audienceThe endovascular technique is used in the first line treatment in many complex aortic pathologies. Its clinical outcome is mostly determined by the appropriate selection of a stent-graft for a specific patient and the operator's experience. New tools are still needed to assist practitioners with decision making before and during procedures. For this purpose, numerical simulation enables the digital reproduction of an endovascular intervention with various degrees of accuracy. In this review, we introduce the basic principles and discuss the current literature regarding the use of numerical simulation for endovascular management of complex aortic diseases. Further, we give the future direction of everyday clinical applications, showing that numerical simulation is about to revolutionize how we plan and carry out endovascular interventions