A Bayesian constitutive model selection framework for biaxial mechanical testing of planar soft tissues: Application to porcine aortic valves.

A variety of constitutive models have been developed for soft tissue mechanics. However, there is no established criterion to select a suitable model for a specific application. Although the model that best fits the experimental data can be deemed the most suitable model, this practice often can be insufficient given the inter-sample variability of experimental observations. Herein, we present a Bayesian approach to calculate the relative probabilities of constitutive models based on biaxial mechanical testing of tissue samples. Forty-six samples of porcine aortic valve tissue were tested using a biaxial stretching setup. For each sample, seven ratios of stresses along and perpendicular to the fiber direction were applied. The probabilities of eight invariant-based constitutive models were calculated based on the experimental data using the proposed model selection framework. The calculated probabilities showed that, out of the considered models and based on the information available through the utilized experimental dataset, the May-Newman model was the most probable model for the porcine aortic valve data. When the samples were further grouped into different cusp types, the May-Newman model remained the most probable for the left- and right-coronary cusps, whereas for non-coronary cusps two models were found to be equally probable: the Lee-Sacks model and the May-Newman model. This difference between cusp types was found to be associated with the first principal component analysis (PCA) mode, where this mode's amplitudes of the non-coronary and right-coronary cusps were found to be significantly different. Our results show that a PCA-based statistical model can capture significant variations in the mechanical properties of soft tissues. The presented framework is applicable to other tissue types, and has the potential to provide a structured and rational way of making simulations population-based.

Ex vivo experimental characterizations for understanding the interrelationship between tissue mechanics and collagen microstructure of porcine mitral valve leaflets.

Unidirectional blood flow in the left side of the heart is regulated by the mitral valve. To better understand the mitral valve function, researchers have examined the structural and mechanical properties of the mitral valve leaflets; however, limitations of the previous studies include the use of mechanics- and structure-altering tissue modifications (e.g., optical clearing) that limit the ability to quantify the unique load-dependent reorientation and realignment of the collagen fibers as well as their interrelation with the valve tissue mechanics. Herein, we aimed to circumvent these limitations by utilizing an integrated polarized-light imaging and biaxial testing system for understanding the mechanics-microstructure interrelationship for porcine mitral valve leaflets. We further performed constitutive modeling and evaluated the accuracy of the affine fiber kinematics theory. From the tissue mechanics perspective, the posterior leaflet was more extensible in the radial direction than the anterior leaflet (14.2% difference in radial tissue stretch), while exhibiting smaller collagen and elastin moduli based on the determined constitutive model parameters. From the collagen microstructure's standpoint, the posterior leaflet had smaller increases in optical anisotropy (closely related to the degree of fiber alignment) than the anterior leaflet (32.8±7.7% vs. 50.0±19.7%). Further, the leaflets were found to possess two distinct fiber families - one family oriented along the circumferential tissue direction, and another more disperse family with a 30°-40° offset from the first fiber family. Finally, affine fiber kinematics consistently underpredicted the collagen fiber reorientations Overall, this study improved our understanding of the mitral valve leaflets that is essential for facilitating tissue-emulated valve replacement and cardiac valve modeling frameworks.

Linking collagen fiber architecture to tissue-level biaxial mechanical behaviors of porcine semilunar heart valve cusps.

The semilunar heart valves regulate the blood flow from the ventricles to the major arteries through the opening and closing of the scallop shaped cusps. These cusps are composed of collagen fibers that act as the primary loading-bearing component. The load-dependent collagen fiber architecture has been previously examined in the existing literature; however, these studies relied on chemical clearing and tissue modifications to observe the underlying changes in response to mechanical loads. In the present study, we address this gap in knowledge by quantifying the collagen fiber orientations and alignments of the aortic and pulmonary cusps through a multi-scale, non-destructive experimental approach. This opto-mechanical approach, which combines polarized spatial frequency domain imaging and biaxial mechanical testing, provides a greater field of view (10-25mm) and faster imaging time (45-50s) than other traditional collagen imaging techniques. The birefringent response of the collagen fibers was fit with a von Mises distribution, while the biaxial mechanical testing data was implemented into a modified full structural model for further analysis. Our results showed that the semilunar heart valve cusps are more extensible in the tissue's radial direction than the circumferential direction under all the varied biaxial testing protocols, together with greater material anisotropy among the pulmonary valve cusps compared to the aortic valve cusps. The collagen fibers were shown to reorient towards the direction of the greatest applied loading and incrementally realign with the increased applied stress. The collagen fiber architecture within the aortic valve cusps were found to be more homogeneous than the pulmonary valve counterparts, reflecting the differences in the physiological environments experienced by these two semilunar heart valves. Further, the von Mises distribution fitting highlighted the presence and contribution of two distinct fiber families for each of the two semilunar heart valves. The results from this work would provide valuable insight into connecting tissue-level mechanics to the underlying collagen fiber architecture-an essential information for the future development of high-fidelity aortic/pulmonary valve computational models.

A Pilot Study on Linking Tissue Mechanics with Load-Dependent Collagen Microstructures in Porcine Tricuspid Valve Leaflets.

The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets' microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV biomechanics society. This pilot study sought to examine the load-dependent collagen fiber architecture of the three TV leaflets, by employing a multiscale, combined experimental approach that utilizes tissue-level biaxial mechanical characterizations, micro-level collagen fiber quantification, and histological analysis. Our results showed that the three TV leaflets displayed greater extensibility in the tissues' radial direction than in the circumferential direction, consistently under different applied biaxial tensions. Additionally, collagen fibers reoriented towards the direction of the larger applied load, with the largest changes in the alignment of the collagen fibers under radially-dominant loading. Moreover, collagen fibers in the belly region of the TV leaflets were found to experience greater reorientations compared to the tissue region closer to the TV annulus. Furthermore, histological examinations of the TV leaflets displayed significant regional variation in constituent mass fraction, highlighting the heterogeneous collagen microstructure. The combined experimental approach presented in this work enables the connection of tissue mechanics, collagen fiber microstructure, and morphology for the TV leaflets. This experimental methodology also provides a new research platform for future developments, such as multiscale models for the TVs, and the design of bioprosthetic heart valves that could better mimic the mechanical, microstructural, and morphological characteristics of the native tricuspid valve leaflets.

Load-dependent collagen fiber architecture data of representative bovine tendon and mitral valve anterior leaflet tissues as quantified by an integrated opto-mechanical system.

The data presented in this article provide load-dependent collagen fiber architecture (CFA) of one representative bovine tendon tissue sample and two representative porcine mitral valve anterior leaflet tissues, and they are stored in a MATLAB MAT-file format. Each dataset contains: (i) the number of pixel points, (ii) the array of pixel's x- and y-coordinates, (iii) the three acquired pixel intensity arrays, and (iv) the Delaunay triangulation for visualization purpose. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of the opto-mechanical characterization of the tissue's CFA's (Jett et al. [1]).

Integration of polarized spatial frequency domain imaging (pSFDI) with a biaxial mechanical testing system for quantification of load-dependent collagen architecture in soft collagenous tissues.

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instrument''s performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p < 0.001. The integrated instrument was further applied to study two representative mitral valve anterior leaflet (MVAL) tissues subjected to various biaxial loads. The fiber orientations within these representative MVAL tissue specimens demonstrated noticeable heterogeneity, with the local fiber orientations dependent upon the sample, the spatial and transmural locations, and the applied loading. Our results also showed that fibers were generally better aligned under equibiaxial (DOA = 0.089 ± 0.036) and circumferentially-dominant loading (DOA = 0.086 ± 0.037) than under the radially-dominant loading (DOA = 0.077 ± 0.034), indicating circumferential predisposition. These novel findings exemplify a deeper understanding of the load-dependent collagen fiber microstructures obtained through the use of the integrated opto-mechanical instrument. STATEMENT OF SIGNIFICANCE: In this study, a novel quantitative opto-mechanical system was developed by combining a polarized Spatial Frequency Domain Imaging (pSFDI) device with a biaxial mechanical tester. The integrated system was used to quantify the load-dependent collagen fiber microstructures in representative tendon and mitral valve anterior leaflet (MVAL) tissues. Our results revealed that MVAL's fiber architectures exhibited load-dependent spatial and transmural heterogeneities, suggesting further microstructural complexity than previously reported in heart valve tissues. These novel findings were possible through the system's ability to, for the first time, capture the load-dependent collagen architecture in the mitral valve anterior leaflet tissue over a wide field of view (e.g., 10 × 10 mm for the MVAL tissue specimens). Such capabilities afford unique future opportunities to improve patient outcomes through concurrent mechanical and microstructural assessments of healthy and diseased tissues in conditions such as heart valve regurgitation and calcification.