Section: New Results

Experiments and Clinical applications

Characterization of mechanical properties of soft tissues

Participants : Jean-Marc Allain [correspondant] , Jean-Sebastien Affagard, Maeva Lopez Poncelas.

Soft tissues - such as skin - have complex mechanical properties: large strains, anisotropy, etc.. Identifying constitutive properties incorporating microstructure effects is very important for applications in medicine (surgery and other therapies) and industry (anti-ageing cosmetics, etc.). This characterization, however, requires complex experiments. We have developed a novel biaxial traction experimental method for mice skin, relying on a sensitivity analysis for determining optimal experimental parameters, including in particular sample size and most informative loading paths. This protocol has already been used on multiple samples, and 3 distinct constitutive laws of increasing complexity have been characterized (Master’s internship of Maeva Lopez).

Another originality in our approach is to place our setup under a microscope to monitor the microstructure evolution during the test. These rich measurements allow detailed comparisons of classical models (such as Holzapfel’s) with our data.

Non-invasive model-based assessment of passive left-ventricular myocardial stiffness in healthy subjects and in patients with non-ischemic dilated cardiomyopathy

Participant : Radomir Chabiniok [correspondant] .

Patient-specific modelling has emerged as a tool for studying heart function, demonstrating the potential to provide non-invasive estimates of tissue passive stiffness. However, reliable use of model-derived stiffness requires sufficient model accuracy and unique estimation of model parameters. In this work we present personalised models of cardiac mechanics, focusing on improving model accuracy, while ensuring unique parametrisation. The influence of principal model uncertainties on accuracy and parameter identifiability was systematically assessed in a group of patients with dilated cardiomyopathy and healthy volunteers. For all cases, we examined three circumferentially symmetric fibre distributions and two epicardial boundary conditions. Our results demonstrated the ability of data-derived boundary conditions to improve model accuracy and highlighted the influence of the assumed fibre distribution on both model fidelity and stiffness estimates. The model personalisation pipeline – based strictly on non-invasive data – produced unique parameter estimates and satisfactory model errors for all cases, supporting the selected model assumptions. The thorough analysis performed enabled the comparison of passive parameters between volunteers and dilated cardiomyopathy patients, illustrating elevated stiffness in diseased hearts.

Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation

Participant : Radomir Chabiniok [correspondant] .

Aging has important deleterious effects on the cardiovascular system. In this work we sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1 -67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28-79 yr). Healthy subjects were divided into age quartiles (1st quartile: 16 yr, 2nd quartile: 17-32 yr, 3rd quartile: 33-48 yr, and 4th quartile: 49 - 64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P 0.182) and ejection fraction (P 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P 0.0001) and young adults (P 0.025). Subjects with LV dysfunction had reduced ejection fraction (P 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P 0.142) but with the addition of an elevated KE in diastasis (P 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. This work has resulted in the publication [24].

Patient-specific computational analysis of ventricular mechanics in pulmonary arterial hypertension

Participant : Martin Genet [correspondant] .

Patient-specific biventricular computational models associated with a normal subject and a pulmonary arterial hypertension (PAH) patient were developed to investigate the disease effects on ventricular mechanics. These models were developed using geometry reconstructed from magnetic resonance (MR) images, and constitutive descriptors of passive and active mechanics in cardiac tissues. Model parameter values associated with ventricular mechanical properties and myofiber architecture were obtained by fitting the models with measured pressure–volume loops and circumferential strain calculated from MR images using a hyperelastic warping method. Results show that the peak right ventricle (RV) pressure was substantially higher in the PAH patient (65 mmHg versus 20 mmHg), who also has a significantly reduced ejection fraction (EF) in both ventricles (left ventricle (LV): 39% versus 66% and RV: 18% versus 64%). Peak systolic circumferential strain was comparatively lower in both the left ventricle (LV) and RV free wall (RVFW) of the PAH patient (LV: −6.8% versus −13.2% and RVFW: −2.1% versus −9.4%). Passive stiffness, contractility, and myofiber stress in the PAH patient were all found to be substantially increased in both ventricles, whereas septum wall in the PAH patient possessed a smaller curvature than that in the LV free wall. Simulations using the PAH model revealed an approximately linear relationship between the septum curvature and the transseptal pressure gradient at both early-diastole and end-systole. These findings suggest that PAH can induce LV remodeling, and septum curvature measurements may be useful in quantifying transseptal pressure gradient in PAH patients. This work has resulted in the publication [25].