A mechanical model to compute elastic modulus of tissues for harmonic motion imaging

Numerous experimental and computational methods have been developed to estimate tissue elasticity. The existing testing techniques are generally classified into in vitro, invasive in vivo and non-invasive in vivo. For each experimental method, a computational scheme is accordingly proposed to calculate mechanical properties of soft biological tissues. Harmonic motion imaging (HMI) is a new technique that performs radio frequency (RF) signal tracking to estimate the localized oscillatory motion resulting from a radiation force produced by focused ultrasound. A mechanical model and computational scheme based on the superposition principle are developed in this paper to estimate the Young's modulus of a tissue mimicking phantom and bovine liver in vitro tissue from the harmonic displacement measured by HMI. The simulation results are verified by two groups of measurement data, and good agreement is shown in each comparison. Furthermore, an inverse function is observed to correlate the elastic modulus of uniform phantoms with amplitude of displacement measured in HMI. The computational scheme is also implemented to estimate 3D elastic modulus of bovine liver in vitro.     

Finite element simulation of interactions between pelvic organs: Predictive model of the prostate motion in the context of radiotherapy

The setting up of predictive models of the pelvic organ motion and deformation may prove an efficient tool in the framework of prostate cancer radiotherapy, in order to deliver doses more accurately and efficiently to the clinical target volume (CTV). A finite element (FE) model of the prostate, rectum and bladder motion has been developed, investigating more specifically the influence of the rectum and bladder repletions on the gland motion. The required organ geometries are obtained after processing the computed tomography (CT) images, using specific softwares. Due to their structural characteristics, a 3D shell discretization is adopted for the rectum and the bladder, whereas a volume discretization is adopted for the prostate. As for the mechanical behavior modelling, first order Ogden hyperelastic constitutive laws for both the rectum and bladder are identified. The prostate is comparatively considered as more rigid and is accordingly modelled as an elastic tissue undergoing small strains. A FE model is then created, accounting for boundary and contact conditions, internal and applied loadings being selected as close as possible to available anatomic data.The order of magnitude of the prostate motion predicted by the FE simulations is similar to the measurements done on a deceased person, accounting for the delineation errors, with a relative error around 8%. Differences are essentially due to uncertainties in the constitutive parameters, pointing towards the need for the setting up of direct measurement of the organs mechanical behavior.     

Bone Tissue Formation under Ideal Conditions in a Scaffold Generated by a Reaction-Diffusion System

The design of porous scaffolds for tissue engineering requires methods to generate geometries in order to control the stiffness and the permeability of the implant among others characteristics. This article studied the potential of the reaction-diffusion systems to design porous scaffolds for bone regeneration. We simulate the degradation of the scaffold material and the formation of new bone tissue over canal-like, spherical and ellipsoid structures obtained by this approach. The simulations show that the degradation and growth rates are affected by the form of porous structures. The results have indicated that the proposed method has potential as a tool to generate scaffolds with internal porosities and is comparable with other methodologies to obtain this type of structures.     

Convergent extension by intercalation without mediolaterally fixed cell motion

We construct and implement a stochastic model of convergent extension, using a minimal set of assumptions on cell behavior. In addition to the basic assumptions of volume conservation, random cell motion, and cell-cell and cell-ECM adhesion, and a non-standard assumption that cytoskeletal polymerization generates an internal pressure tending to keep cells convex, we find that we need only two conditions for convergent extension. (1) Each cell type has a particular aspect ratio towards which it regulates its geometry. We do not require that cells align in a specific orientation, e.g. to be oriented mediolaterally. (2) The elongating tissue is composed of cells that prefer to be elongated, and these cells must be accompanied by cells which prefer to be round. The latter effectively provide a boundary to capture. In simulations, our model tissue extends and converges to a stacked arrangement of elongated cells one cell wide, an arrangement which is seen in ascidian notochords, but which has not been observed in other models. This arrangement is achieved without any direct mediolateral bias other than that which is provided by the physical edge of the adjacent tissue.     

Predicting the external formation of a bone fracture callus: an optimisation approach

The formation of a fracture callus in vivo tends to form in a structurally efficient manner distributing tissues where mechanical stimulus persists. Therefore, it is proposed that the formation of a fracture callus can be modelled in silico by way of an optimisation algorithm. This was tested by generating a finite element model of a transversal bone fracture embedded in a large tissue domain which was subjected to axial, bending and torsional loads. It was found that the relative fragment motion induced a compressive strain field in the early callus tissue which could be utilised to simulate the formation of external callus structures through an iterative optimisation process of tissue maintenance and removal. The phenomenological results showed a high level of congruence with in vivo healing patterns found in the literature. Consequently, the proposed strategy shows potential as a means of predicting spatial bone healing phenomena for pre-clinical testing.     

Adaptive Mesh Expansion Model (AMEM) for Liver Segmentation from CT Image

This study proposes a novel adaptive mesh expansion model (AMEM) for liver segmentation from computed tomography images. The virtual deformable simplex model (DSM) is introduced to represent the mesh, in which the motion of each vertex can be easily manipulated. The balloon, edge, and gradient forces are combined with the binary image to construct the external force of the deformable model, which can rapidly drive the DSM to approach the target liver boundaries. Moreover, tangential and normal forces are combined with the gradient image to control the internal force, such that the DSM degree of smoothness can be precisely controlled. The triangular facet of the DSM is adaptively decomposed into smaller triangular components, which can significantly improve the segmentation accuracy of the irregularly sharp corners of the liver. The proposed method is evaluated on the basis of different criteria applied to 10 clinical data sets. Experiments demonstrate that the proposed AMEM algorithm is effective and robust and thus outperforms six other up-to-date algorithms. Moreover, AMEM can achieve a mean overlap error of 6.8% and a mean volume difference of 2.7%, whereas the average symmetric surface distance and the root mean square symmetric surface distance can reach 1.3 mm and 2.7 mm, respectively.     

An anisotropic internal-external bone adaptation model based on a combination of CAO and continuum damage mechanics technologies

In this work, a complete internal-external bone-remodelling scheme is presented and implemented into a finite element code. This model uses a combination of an anisotropic internal remodelling model based on a new Continuum "Damage-Repair" theory and an external adaptation approach that follows the idea, early introduced by Mattheck et al., to simulate the growth behaviour of biological systems, known as CAO method. This combined scheme qualitatively resembles most of the main features of the bone adaptive behaviour, like the bone mass distribution (heterogeneity and porosity), the directional internal structure (anisotropy), the alignment of the microstructure with the constitutive principal directions and these with those of the stress tensor when permanently loaded by a unique stress state (Wolff's law). It is also thermodynamically consistent, fulfilling a principle of minimum mechanical dissipation. Finally, the comparison between the predicted results and the ones obtained by different experimental tests allows us to conclude that this model is able of reproducing qualitatively the global behaviour of bone tissue when subjected to external mechanical loads.     

Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model

We compared imaging and pathological changes between argon–helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.     

Predicting the external formation of a bone fracture callus: an optimisation approach

The formation of a fracture callus in vivo tends to form in a structurally efficient manner distributing tissues where mechanical stimulus persists. Therefore, it is proposed that the formation of a fracture callus can be modelled in silico by way of an optimisation algorithm. This was tested by generating a finite element model of a transversal bone fracture embedded in a large tissue domain which was subjected to axial, bending and torsional loads. It was found that the relative fragment motion induced a compressive strain field in the early callus tissue which could be utilised to simulate the formation of external callus structures through an iterative optimisation process of tissue maintenance and removal. The phenomenological results showed a high level of congruence with in vivo healing patterns found in the literature. Consequently, the proposed strategy shows potential as a means of predicting spatial bone healing phenomena for pre-clinical testing.     

新型可降解锌合金内固定系统用于犬下颌骨骨折固定的研究

目的:探讨新型可降解锌合金内固定系统用于犬下颌骨骨折固定的可行性。方法:选择比格犬12只,并将其随机分为两组,其中6只为锌合金实验组,6只为钛合金对照组。每只比格犬的下颌作左右两个骨折内固定模型,每侧骨折模型使用一套小型四孔直连内固定产品。分别于术后即刻、术后4周、12周拍X片。于术前、术后4周、12周、24周抽血检测微量元素锌。于术后12周、24周分批次将动物安乐死,取下颌骨块行Micro-CT检测,取动物重要脏器和内固定周围软组织做病理切片。结果:全程动物无脱落,实验组与对照组骨折均临床愈合。X线图像及Micro-CT显示实验组与对照组的内固定效果比较差异无统计学意义(P0.05)。锌合金表面有明显的降解产物,Micro-CT测量锌合金的板钉初始体积为155.8±1.536 mm~3,12周体积为147.1±0.9893 mm~3,24周体积为137±5.365 mm~3,降解率12.07%,随着植入后时间的延长显著下降(P0.05),而钛合金板钉体积无显著变化。实验组及对照组心、肝、肾及植入物板周软组织均未见异常。血清锌离子浓度在正常范围内略有上升,各时间节点比较差异无统计学意义(P0.05)。结论:可降解锌合金内固定系统可以对犬下颌骨骨折提供稳固的固定,可降解锌合金在下颌骨部位具有一定的降解性能,血液中锌离子未见明显异常升高,对心、肝、肾及植入物周围软组织无毒性作用。     

Comparison of the linear finite element prediction of deformation and strain of human cancellous bone to 3D digital volume correlation measurements

The mechanical properties of cancellous bone and the biological response of the tissue to mechanical loading are related to deformation and strain in the trabeculae during function. Due to the small size of trabeculae, their motion is difficult to measure. To avoid the need to measure trabecular motions during loading the finite element method has been used to estimate trabecular level mechanical deformation. This analytical approach has been empirically successful in that the analytical models are solvable and their results correlate with the macroscopically measured stiffness and strength of bones. The present work is a direct comparison of finite element predictions to measurements of the deformation and strain at near trabecular level. Using the method of digital volume correlation, we measured the deformation and calculated the strain at a resolution approaching the trabecular level for cancellous bone specimens loaded in uniaxial compression. Smoothed results from linearly elastic finite element models of the same mechanical tests were correlated to the empirical three-dimensional (3D) deformation in the direction of loading with a coefficient of determination as high as 97% and a slope of the prediction near one. However, real deformations in the directions perpendicular to the loading direction were not as well predicted by the analytical models. Our results show, that the finite element modeling of the internal deformation and strain in cancellous bone can be accurate in one direction but that this does not ensure accuracy for all deformations and strains.     

Search for critical loading condition of the spine--a meta analysis of a nonlinear viscoelastic finite element model

The relative vulnerability of spinal motion segments to different loading combinations remains unknown. The meta-analysis described here using the results of a validated L2-L3 nonlinear viscoelastic finite element model was designed to investigate the critical loading and its effect on the internal mechanics of the human lumbar spine. A Box-Behnken experimental design was used to design the magnitude of seven independent variables associated with loads, rotations and velocity of motion. Subsequently, an optimization method was used to find the primary and secondary variables that influence spine mechanical output related to facet forces, disc pressure, ligament forces, annulus matrix compressive/shear stresses and anulus fibers strain. The mechanical responses with respect to the two most-relevant variables were then regressed linearly using the response surface quadratic model. Axial force and sagittal rotation were identified as the most-relevant variables for mechanical responses. The procedure developed can be used to find the critical loading for finite element models with multi input variables. The derived meta-models can be used to predict the risk associated with various loading parameters and in setting safer load limits.     

An Anisotropic Internal-External Bone Adaptation Model Based on a Combination of CAO and Continuum Damage Mechanics Technologies

Abstract

In this work, a complete internal-external bone-remodelling scheme is presented and implemented into a finite element code. This model uses a combination of an anisotropic internal remodelling model based on a new Continuum "Damage-Repair" theory and an external adaptation approach that follows the idea, early introduced by Mattheck et ah, to simulate the growth behaviour of biological systems, known as CAO method. This combined scheme qualitatively resembles most of the main features of the bone adaptive behaviour, like the bone mass distribution (heterogeneity and porosity), the directional internal structure (anisotropy), the alignment of the microstructure with the constitutive principal directions and these with those of the stress tensor when permanently loaded by a unique stress state (WolfFs law). It is also thermodynamically consistent, fulfilling a principle of minimum mechanical dissipation. Finally, the comparison between the predicted results and the ones obtained by different experimental tests allows us to conclude that this model is able of reproducing qualitatively the global behaviour of bone tissue when subjected to external mechanical loads.     

Protein-ligand dynamics. A 96 picosecond simulation of a myoglobin-xenon complex

A 96 picosecond dynamics trajectory of myoglobin with five xenon-probe ligands in internal cavities is examined to study the effect of protein motions on ligand motion and internal cavity fluctuations. Average structural and energetic properties indicate that the simulation is well behaved. The average protein volume is similar to the volume of the X-ray model and the main-chain atom root-mean-square deviation between the X-ray model and the average dynamical structure is 1.25 A. The protein volume oscillates 3 to 4% around the volume of the X-ray structure. These fluctuations lead to changes in the internal free volume and in the size, shape and location of atom-sized cavity features. Transient cavities produced in the simulation have a crucial role in the movement of two of the ligands. One of the ligands escapes to the protein surface, whilst a second ligand travels through the protein interior. Complex gating processes involving several protein residues are responsible for producing the necessary pores through which the ligand passes between transient cavities or packing defects.     

Scale-dependent mechanical properties of native and decellularized liver tissue

Decellularization, a technique used in liver regenerative medicine, is the removal of all the cellular components from a tissue or organ, leaving behind an intact structure of extracellular matrix. The biomechanical properties of this novel scaffold material are currently unknown and are important due to the mechanosensitivity of liver cells. Characterizing this material is important for bioengineering liver tissue from this decellularized scaffold as well as creating new 3-dimensional mimetic structures of liver extracellular matrix. This study set out to characterize the biomechanical properties of perfused liver tissue in its native and decellularized states on both a macro- and nano-scale. Poroviscoelastic finite element models were then used to extract the fluid and solid mechanical properties from the experimental data. Tissue-level spherical indentation-relaxation tests were performed on 5 native livers and 8 decellularized livers at two indentation rates and at multiple perfusion rates. Cellular-level spherical nanoindentation was performed on 2 native livers and 1 decellularized liver. Tissue-level results found native liver tissue to possess a long-term Young’s modulus of 10.5 kPa and decellularized tissue a modulus of 1.18 kPa. Cellular-level testing found native tissue to have a long-term Young’s modulus of 4.40 kPa and decellularized tissue to have a modulus of 0.91 kPa. These results are important for regenerative medicine and tissue engineering where cellular response is dependent on the mechanical properties of the engineered scaffold.     

Bayesian estimation of probabilistic atlas for tissue segmentation

Automatic anatomical brain image segmentation is still a challenge. In particular, algorithms have to address the partial volume effect (PVE) as well as the variability of the gray level of internal brain structures which may appear closer to gray matter (GM) than white matter (WM). Atlas based segmentation is one solution as it brings prior information. For such tasks, probabilistic atlases are very useful as they take account of the PVE information. In this paper, we provide a detailed analysis of a generative statistical model based on dense deformable templates that represents several tissue types observed in medical images. The inputs are gray level data whereas our atlas is composed of both an estimation of the deformation metric and probability maps of each tissue (called class). This atlas is used to guide the tissue segmentation of new images. Experiments are shown on brain T1 MRI datasets. This method only requires approximate pre-registration, as the latter is done jointly with the segmentation. Note however that an approximate registration is a reasonable pre-requisite given the application.     

Coevolution of male and female reproductive structures in Drosophila

The morphology of male genitalia whilst stable within species, exhibits huge interspecific variation. This variation is likely to be as a result of sexual selection due to the direct involvement of these reproductive structures in mating and sperm transfer. In contrast, internal soft tissue components of the genitalia are generally poorly investigated as they are not directly involved in physical and mechanical adequacy during sperm transfer. However, these soft tissue structures may also drive differential male–female interactions, particularly in internally fertilising organisms where females have the ability to store sperm and bias male reproductive success. In this paper we use the drosophila model to investigate the role of male and female reproductive elements in sexual selection. Our meta-analysis supplemented with additional new data clearly shows that within species, sperm length versus testis length, and sperm length versus seminal receptacle length, are highly correlated. Thus, independent of the phylogenetic relationship among species, gamete evolution is likely to result in sexual selection interactions that drive the evolution of internal reproductive components in both sexes. Our results and discussion of the literature highlight the importance of considering internal soft structures that may influence fertilisation, when investigating selective forces acting on the evolution of reproductive traits.     

Simulation of molecular crowding effects on an Alzheimer's α-amyloid peptide

Fibril formation by the Alzheimer's β-amyloid (Aβ) peptide in brain tissue is integral to the Alzheimer's disease pathology. Understanding the conformational properties and the mechanisms triggering aggregation of the Aβ peptides, at an atomic level of detail, is of crucial importance for the design of effective therapeutic agents against this disease. In this work, the conformational transitions and dynamic properties of an amyloidogenic peptide fragment (Aβ_10-35) were studied by molecular dynamics simulations in systems modeling infinite dilution and the presence of macromolecular crowding agents (CA). The model system consists of the peptide described with an atomistic force field, the CA represented by inert, quasi-hard spheres and a continuum solvent model. This combined model allowed the simulations to be extended to 100 ns each. Simulations were carried out starting from a completely extended structure, a β-strand structure, and four nuclear magnetic resonance structures in dilute aqueous solution. For all structures, two additional simulations were performed that included the inert CA in the solution and occupied approx 30 and 40% of the volume, respectively. For two of the nuclear magnetic resonance structures, additional simulations were carried out with 35% volume fraction of CA to further examine the diffusive behavior of the peptide. The peptide adopted a collapsed coil conformation in all simulations. The results of the simulations in dilute solution showed reasonable qualitative agreement with experimental and other simulation results, whereas the presence of volume excluding agents resulted in some distinct changes in properties (e.g., an increase in the appearance of transient β-structure or decreases in diffusivity with increasing CA concentration). At the same time, internal motion such as order parameter or atomic root mean square fluctuations showed less systematic responses to volume exclusion.     

Improved prediction of the collagen fiber architecture in the aortic heart valve

Living tissues show an adaptive response to mechanical loading by changing their internal structure and morphology. Understanding this response is essential for successful tissue engineering of load-bearing structures, such as the aortic valve. In this study, mechanically induced remodeling of the collagen architecture in the aortic valve was investigated. It was hypothesized that, in uniaxially loaded regions, the fibers aligned with the tensile principal stretch direction. For biaxial loading conditions, on the other hand, it was assumed that the collagen fibers aligned with directions situated between the principal stretch directions. This hypothesis has already been applied successfully to study collagen remodeling in arteries. The predicted fiber architecture represented a branching network and resembled the macroscopically visible collagen bundles in the native leaflet. In addition, the complex biaxial mechanical behavior of the native valve could be simulated qualitatively with the predicted fiber directions. The results of the present model might be used to gain further insight into the response of tissue engineered constructs during mechanical conditioning.