Interplay between activity, elasticity, and liquid transport in self-contractile biopolymer gels.

Active gels play an important role in biology and in inspiring biomimetic active materials, due to their ability to change shape, size, and create their own morphology. We study a particular class of active gels, generated by polymerizing actin in the presence of cross-linkers and clusters of myosin as molecular motors, which exhibit large contractions. The relevant mechanics for these highly swollen gels is the result of the interplay between activity and liquid flow: gel activity yields a structural reorganization of the gel network and produces a flow of liquid that eventually exits from the gel boundary. This dynamics inherits lengthscales that are typical of the liquid flow processes. The analyses we present provide insights into the contraction dynamics, and they focus on the effects of the geometry on both gel velocity and fluid flow.

Geometry Does Impact on the Plane Strain Directions of the Human Left Ventricle, Irrespective of Disease.

The directions of primary strain lines of local deformation in Epicardial and Endocardial layers have been the subject of debate in recent years. Different methods led to different conclusions and a complete assessment of strain direction patterns in large and variable (in terms of pathology) cohorts of healthy and diseased patients is still lacking. Here, we use local deformation tensors in order to evaluate the angle of strain lines with respect to the horizontal circumferential direction in both Epi- and Endo-layers. We evaluated this on a large group of 193 subjects including 82 healthy control and 111 patients belonging to a great variety of pathological conditions. We found that Epicardial strain lines obliquely directed while those of Endocardium are almost circumferential. This result occurs irrespective of pathological condition. We propose that the geometric vinculum characterizing Endocardium and Epicardium in terms of different lever arm length and orientation of muscular fibers during contraction inescapably requires Endocardial strain lines to be circumferentially oriented and this is corroborated by experimental results. Further investigations on transmural structure of myocytes could couple results presented here in order to furnish additional experimental explanations.

Stress-free morphing by means of compatible distortions.

We study the morphing of three-dimensional objects within the framework of nonlinear elasticity with large distortions. A distortion field induces a target metric, and the configuration which is effectively realized by a material body is the one that minimizes the distance, measured through the elastic energy, between the target metric and the actual one. Morphing through distortions might have a paramount feature: the resulting configurations might be stress-free; if this is the case, the distortions field is called compatible. We maintain that the morphing through compatible distortions is a key strategy exploited by many soft biological materials, which can exhibit very large shape-change in response to distortions controlled by stimuli such as chemicals or temperature changes, while keeping their stress state almost null. Thus, the study of compatible distortions, and of the related shape-changes, is quite important. Here, we show a blueprint for stress-free morphing based on the notions of metric tensor and of Riemann curvature which can be used to design large morphing of three-dimensional objects.

Local and global energies for shape analysis in medical imaging.

In a previous contribution, a new Riemannian shape space, named TPS space, was introduced to perform statistics on shape data. This space was endowed with a Riemannian metric and a flat connection, with torsion, compatible with the given metric. This connection allows the definition of a Parallel Transport of the deformation compatible with the three-fold decomposition in spherical, deviatoric, and non-affine components. Such a parallel transport also conserves the Γ-energy, strictly related to the total elastic strain energy stored by the body in the original deformation. A new approach is here presented in order to calculate the bending energy on the body alone (body bending energy) and to restrict it exclusively within physical boundaries of objects involved in the deformation analysis. The novelty of this new procedure resides in the fact that we propose a new metric to be preserved during the TPS direct transport. This allows transporting the shape change more coherently with the mechanical meaning of the deformation. The geometry of the TPS space is then further discussed in order to better represent the relationship between the Γ-energy, the strain energy, and the so-called bending energy densities.

Non-invasive prediction of genotype positive-phenotype negative in hypertrophic cardiomyopathy by 3D modern shape analysis.

NEW FINDINGS: What is the central question of this study? Can impaired deformational indicators for genotype positive for hypertrophic cardiomyopathy in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-) be determined using non-invasive 3D echocardiography? What is the main finding and its importance? Using 3D-STE and modern shape analysis, peculiar deformational impairments can be detected in G+LVH- subjects that can be classified with good accuracy. Moreover, the patterns of impairment are located mainly on the apical region in agreement with other evidence coming from previous biomechanical investigations. ABSTRACT: We propose a non-invasive procedure for predicting genotype positive for hypertrophic cardiomyopathy (HCM) in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-); the procedure is based on the enhanced analysis of medical imaging from 3D speckle tracking echocardiography (3D-STE). 3D-STE, due to its low quality images, has not been used so far to detect effectively the G+LVH- condition. Here, we post-processed echocardiographic images exploiting the tools of modern shape analysis, and we studied the motion of the left ventricle (LV) during an entire cycle. We enrolled 82 controls, 21 HCM patients and 11 G+LVH- subjects. We followed two steps: (i) we selected the most impaired regions of the LV by analysing its strains; and (ii) we used shape analysis on these regions to classify the subjects. The G+LVH- subjects showed different trajectories and deformational attributes. We found high classification performance in terms of area under the receiver operating characteristic curve (∼90), sensitivity (∼78) and specificity (∼79). Our results showed that (i) G+LVH- subjects present important deformational impairments relative to healthy controls and (ii) modern shape analysis can efficiently predict genotype by means of a non-invasive and inexpensive technique such as 3D-STE.

The heart function as a motor-brake system.

The controversy between passive and active ventricular filling has been debated for decades and the question about the existence of an active diastole remains open. In this work, we advocate the model of active diastole by considering the heart as a suction pump and we add some more clues to support this point of view by the analysis of the pressure-volume (PV) loops of the left heart, comprising of the left ventricle (LV) and atrium (LA). Our working hypothesis is based on the dichotomy motor-brake: the cardiac muscle can act as a motor, when shortening against a load, or as a brake, when lengthening to a load. We discuss our hypothesis by means of a lumped model of the left heart, where both chambers are considered as hollow spherical shells. The notion of active stretch, introduced to describe the contractile behavior of the muscle fibers, plays a major role in our model. Then, the contraction of the muscle is related to the pressure and volume of the chamber through a nonlinear hyperelastic energy density function. Despite its simplicity, the model enlightens some important features of the LV-LA coupling and of the pumping function of the heart. Based on experimental PV data of the left heart of a normal human subject, it is shown that the contraction patterns of the LV and LA are synchronized with each other and have distinguishing features in each phase of the cardiac cycle. These results highlight the interplay between the two chambers and support the idea that the heart may act as a suction pump functioning in turn as a motor or a brake in order to meet specific demands in each phase of the cardiac cycle.

The decomposition of deformation: New metrics to enhance shape analysis in medical imaging.

In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between Centroid Size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall's size-and-shape space without losing Kendall's original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy.

Driving water cavitation in a hydrogel cavity.

We study the dynamics of the dehydration process of a hydrogel with a cavity filled with water. We identify two transient phases: the first one dominated by an inflatable-balloon deformation mode, and the second by a suction effect, determining highly not homogeneous deformation modes of the hydrogel walls. This last phase triggers negative pressures into the cavity up to the typical values of water cavitation. An analysis of the factors allowing cavitation pressure to form inside the cavity is proposed, to allow for precise tuning of the key geometrical and material parameters.

Statistical shape modeling of the left ventricle: myocardial infarct classification challenge.

Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to (1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and (2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website1.

Morphologically normalized left ventricular motion indicators from MRI feature tracking characterize myocardial infarction.

We characterized motion attributes arising from LV spatio-temporal analysis of motion distributions in myocardial infarction. Time-varying 3D finite element shape models were obtained in 300 Controls and 300 patients with myocardial infarction. Inter-individual left ventricular shape differences were eliminated using parallel transport to the grand mean of all cases. The first three principal component (PC) scores were used to characterize trajectory attributes. Scores were tested with ANOVA/MANOVA using patient disease status (Infarcts vs. Controls) as a factor. Infarcted patients had significantly different magnitude, orientation and shape of left ventricular trajectories in comparison to Controls. Significant differences were found for the angle between PC scores 1 and 2 in the endocardium, and PC scores 1 and 3 in the epicardium. The largest differences were found in the magnitude of endocardial motion. Endocardial PC scores in shape space showed the highest classification power using support vector machine, with higher total accuracy in comparison to previous methods. Shape space performed better than size-and-shape space for both epicardial and endocardial features. In conclusion, LV spatio-temporal motion attributes accurately characterize the presence of infarction. This approach is easily generalizable to different pathologies, enabling more precise study of the pathophysiological consequences of a wide spectrum of cardiac diseases.

Homeostatic Left Heart integration and disintegration links atrio-ventricular covariation's dyshomeostasis in Hypertrophic Cardiomyopathy.

Left ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.

New finite element study protocol: Clinical simulation of orthodontic tooth movement.

The aim of this work was to model tooth movement in a more clinically-exact fashion, thanks to the use of new IT tools and imaging systems (cone-beam). Image segmentation and 3D reconstruction now enable us to model the anatomy realistically, while finite element (FE) analysis makes it possible to evaluate stresses and their distribution on the level of the tooth, the periodontal ligament (PDL) and the alveolar bone when a force is applied. The principle is to monitor tooth movement by obtaining optical impressions at each stage of treatment. The model corresponds to a genuine clinical situation. FE analysis is correlated with the clinically-observed displacement. The protocol remains long and complex. It nevertheless makes it possible to obtain, throughout the duration of treatment, patient-specific models that can be exploited using finite element methods. It requires further validation in more thorough studies but offers interesting prospects: precise study of induced tooth movement, distribution of stresses in the PDL, and development of a customized previsualization tool.

Left Atrial trajectory impairment in Hypertrophic Cardiomyopathy disclosed by Geometric Morphometrics and Parallel Transport.

The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction.

Modeling and simulation of fish swimming with active muscles.

Our goal is to reproduce the key features of carangiform swimming by modeling muscle functioning using the notion of active distortions, thus emphasizing the kinematical role of muscle, the generation of movement, rather than the dynamical one, the production of force. This approach, already proposed to model the action of muscles in different contexts, is here tested again for the problem of developing an effective and reliable framework to model and simulate swimming. A proper undulatory movement of a fish-like body is reproduced by defining a pattern of distortions, tuned in both space and time, meant to model the muscles activation which produce the flexural motion of body fish; eventually, interactions with the surrounding water yields the desired thrust. Carangiform swimmers have a relatively inflexible anterior body section and a generally flat, flexible posterior section. Because of this configuration, undulations sent rearward along the body attain a significant amplitude only in the posterior section. We compare the performances of different swimming gaits, and we are able to find some important relations between key parameters such as frequencies, wavelength, tail amplitude, and the achieved swim velocity, or the generated thrust, which summarize the swimming performance. In particular, an interesting relation is found between the Strouhal number and the wavelength of muscles activation. We highlight the muscle function during fish locomotion describing the activation of muscles and the relation between the force production and the shortening-lengthening cycle of muscle. We found a great accordance between results and empirical relations, giving an implicit validation of our models.

Cope's Rule and the Universal Scaling Law of Ornament Complexity.

Luxuriant, bushy antlers, bizarre crests, and huge, twisting horns and tusks are conventionally understood as products of sexual selection. This view stems from both direct observation and from the empirical finding that the size of these structures grows faster than body size (i.e., ornament size shows positive allometry). We contend that the familiar evolutionary increase in the complexity of ornaments over time in many animal clades is decoupled from ornament size evolution. Increased body size comes with extended growth. Since growth scales to the quarter power of body size, we predicted that ornament complexity should scale according to the quarter power law as well, irrespective of the role of sexual selection in the evolution and function of the ornament. To test this hypothesis, we selected three clades (ammonites, deer, and ceratopsian dinosaurs) whose species bore ornaments that differ in terms of the importance of sexual selection to their evolution. We found that the exponent of the regression of ornament complexity to body size is the same for the three groups and is statistically indistinguishable from 0.25. We suggest that the evolution of ornament complexity is a by-product of Cope's rule. We argue that although sexual selection may control size in most ornaments, it does not influence their shape.

Structure of tracheae and the functional implications for collapse in the American cockroach.

The tracheal tubes of insects are complex and heterogeneous composites with a microstructural organization that affects their function as pumps, valves, or static conduits within the respiratory system. In this study, we examined the microstructure of the primary thoracic tracheae of the American cockroach (Periplaneta americana) using a combination of scanning electron microscopy and light microscopy. The organization of the taenidia, which represents the primary source of structural reinforcement of the tracheae, was analyzed. We found that the taenidia were more disorganized in the regions of highest curvature of the tracheal tube. We also used a simple finite element model to explore the effect of cross-sectional shape and distribution of taenidia on the collapsibility of the tracheae. The eccentricity of the tracheal cross-section had a stronger effect on the collapse properties than did the distribution of taenidia. The combination of the macro-scale geometry, meso-scale heterogeneity, and microscale organization likely enables rhythmic tracheal compression during respiration, ultimately driving oxygen-rich air to cells and tissues throughout the insect body. The material design principles of these natural composites could potentially aid in the development of new bio-inspired microfluidic systems based on the differential collapse of tracheae-like networks.

Variation in the shape and mechanical performance of the lower jaws in ceratopsid dinosaurs (Ornithischia, Ceratopsia).

Ceratopsidae represents a group of quadrupedal herbivorous dinosaurs that inhabited western North America and eastern Asia during the Late Cretaceous. Although horns and frills of the cranium are highly variable across species, the lower jaw historically has been considered to be relatively conservative in morphology. Here, the lower jaws from 58 specimens representing 21 ceratopsoid taxa were sampled, using geometric morphometrics and 2D finite element analysis (FEA) to explore differences in morphology and mechanical performance across Ceratopsoidea (the clade including Ceratopsidae, Turanoceratops and Zuniceratops). Principal component analyses and non-parametric permuted manovas highlight Triceratopsini as a morphologically distinct clade within the sample. A relatively robust and elongate dentary, a larger and more elongated coronoid process, and a small and dorso-ventrally compressed angular characterize this clade, as well as the absolutely larger size. By contrast, non-triceratopsin chasmosaurines, Centrosaurini and Pachyrhinosaurini have similar morphologies to each other. Zuniceratops and Avaceratops are distinct from other taxa. No differences in size between Pachyrhinosaurini and Centrosaurini are recovered using non-parametric permuted anovas. Structural performance, as evaluated using a 2D FEA, is similar across all groups as measured by overall stress, with the exception of Triceratopsini. Shape, size and stress are phylogenetically constrained. A longer dentary as well as a long coronoid process result in a lower jaw that is reconstructed as relatively much more stressed in triceratopsins.

Digging adaptation in insectivorous subterranean eutherians. The enigma of Mesoscalops montanensis unveiled by geometric morphometrics and finite element analysis.

The enigmatic Early Miocene fossorial mammal Mesoscalops montanensis shows one of the most modified humeri among terrestrial mammals. It has been suggested, on qualitative considerations, that this species has no extant homologues for humerus kinematics and that, functionally, the closest extant group is represented by Chrysochloridae. We combine here three dimensional geometric morphometrics, finite element analysis and phylogenetic comparative methods to explore the shape and mechanical stress states of Mesoscalops montanensis as well as of extant and extinct Talpidae and Chrysochloridae under realistic digging simulations. Evolutionary convergence analyses reveal that the shape of Mesoscalops montanensis represents a unique morphology in the context of fossorial mammals and that its functional performance, albeit superficially similar to that of extant Chrysochloridae, still represents a nonconvergent optimum for adaptation to digging.