The mechanical response of the cornea subjected to a non-contact air-jet tonometry diagnostic test represents an interplay between its geometry, the corneal material behavior and the loading. The objective is to study this interplay to better understand and interpret the results obtained with a non-contact tonometry test. A patient-specific finite element model of a healthy eye, accounting for the load free configuration, was used. The corneal tissue was modeled as an anisotropic hyperelastic material with two preferential directions. Three different sets of parameters within the human experimental range obtained from inflation tests were considered. The influence of the IOP was studied by considering four pressure levels (10–28 mmHg) whereas the influence of corneal thickness was studied by inducing a uniform variation (300–600 microns). A Computer Fluid Dynamics (CFD) air-jet simulation determined pressure loading exerted on the anterior corneal surface. The maximum apex displacement showed a linear variation with IOP for all materials examined. On the contrary, the maximum apex displacement followed a cubic relation with corneal thickness. In addition, a significant sensitivity of the apical displacement to the corneal stiffness was also obtained. Explanation to this behavior was found in the fact that the cornea experiences bending when subjected to an air-puff loading, causing the anterior surface to work in compression whereas the posterior surface works in tension. Hence, collagen fibers located at the anterior surface do not contribute to load bearing. Non-contact tonometry devices give useful information that could be misleading since the corneal deformation is the result of the interaction between the mechanical properties, IOP, and geometry. Therefore, a non-contact tonometry test is not sufficient to evaluate their individual contribution and a complete in-vivo characterization would require more than one test to independently determine the membrane and bending corneal behavior.

An ascending thoracic aortic aneurysm (ATAA) is a serious medical condition which, more often than not, requires surgery. Aneurysm diameter is the primary clinical criterion for determining when surgical intervention is necessary but, biomechanical studies have suggested that the diameter criterion is insufficient. This manuscript presents a method for obtaining the patient specific wall stress distribution of the ATAA and the retrospective rupture risk for each patient. Five human ATAAs and the preoperative dynamic CT scans were obtained during elective surgeries to replace each patient's aneurysm with a synthetic graft. The material properties and rupture stress for each tissue sample were identified using bulge inflation tests. The dynamic CT scans were used to generate patient specific geometries for a finite element (FE) model of each patient's aneurysm. The material properties from the bulge inflation tests were implemented in the FE model and the wall stress distribution at four different pressures was estimated. Three different rupture risk assessments were compared: the maximum diameter, the rupture risk index, and the overpressure index. The peak wall stress values for the patients ranged from 28% to 94% of the ATAA's failure stress. The rupture risk and overpressure indices were both only weakly correlated with diameter (ρ=-0.29, both cases). In the future, we plan to conduct a large experimental and computational study that includes asymptomatic patients under surveillance, patients undergoing elective surgery, and patients who have experienced rupture or dissection to determine if the rupture risk index or maximum diameter can meaningfully differentiate between the groups.

This work presents a novel methodology for building a three-dimensional patient-specific eyeball model suitable for performing a fully automatic finite element (FE) analysis of the corneal biomechanics. The reconstruction algorithm fits and smooths the patient's corneal surfaces obtained in clinic with corneal topographers and creates an FE mesh for the simulation. The patient's corneal elevation and pachymetry data is kept where available, to account for all corneal geometric features (central corneal thickness-CCT and curvature). Subsequently, an iterative free-stress algorithm including a fiber's pull-back is applied to incorporate the pre-stress field to the model. A convergence analysis of the mesh and a sensitivity analysis of the parameters involved in the numerical response is also addressed to determine the most influential features of the FE model. As a final step, the methodology is applied on the simulation of a general non-commercial non-contact tonometry diagnostic test over a large set of 130 patients-53 healthy, 63 keratoconic (KTC) and 14 post-LASIK surgery eyes. Results show the influence of the CCT, intraocular pressure (IOP) and fibers (87%) on the numerical corneal displacement (U(Num)) the good agreement of the U(Num) with clinical results, and the importance of considering the corneal pre-stress in the FE analysis. The potential and flexibility of the methodology can help improve understanding of the eye biomechanics, to help to plan surgeries, or to interpret the results of new diagnosis tools (i.e., non-contact tonometers).

Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p < 0.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations. In this work, we explore the limitations of these approaches to estimate ion channel dynamics and maximum current conductances and how they could be overcome by using multiscale simulations of experimental protocols. Four human ventricular cell models, namely ten Tusscher and Panfilov (2006), Grandi et al. (2010), O'Hara et al. (2011), and Carro et al. (2011), were used. Two problems involving scales from ion channels to tissue were investigated: 1) characterization of L-type calcium voltage-dependent inactivation I; 2) identification of major ionic conductance contributors to steady-state AP markers, including APD, APD, APD, APD, Triangulation and maximal and minimal values of V and dV/dt during the AP (V, V, dV/dt, dV/dt). Our results show that: 1) I inactivation characteristics differed significantly when calculated from model equations and from simulations reproducing the experimental protocols. 2) Large differences were found in the ionic currents contributors to APD, Triangulation, V, dV/dt and dV/dt between single cells and 1D-tissue. When proposing any new model formulation, or evaluating an existing model, consistency between simulated and experimental data should be verified considering all involved effects and scales.

Indentation tests cannot characterize the changes in the corneal collagen scaffold caused by the CXL, but the uniaxial test can. However, indentation tests can assess the recovery of keratocyte density after CXL. [J Refract Surg. 2017;33(3):184-192.].

The influence of each ischemic component (hypoxia, hyperkalemia, and acidosis) on arrhythmogenesis is controversial and difficult to study experimentally. In the present study, we investigate how the different ischemic components affect the vulnerable window (VW) for reentry using computational simulations. Simulations were performed in a 3D biventricular model that includes a realistic ischemic region and the His-Purkinje conduction system. At the cellular level, we used a modified version of the O'Hara action potential model adapted to simulate acute ischemia. Three different levels of ischemia were simulated: mild, moderate, and severe. The effects on the width of the VW of each ischemic parameter were analyzed. The model allowed us to obtain a realistic reentrant pattern corresponding to ventricular tachycardia in all simulations. Results suggest that the ischemic level plays an important role in the generation of reentries. Furthermore, hypoxia has the most significant effect on the width of the VW. The presence of Purkinje system is key to the generation of reentries.

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